In August 2015, a 50-year-old man developed an increase in size of the right testicle without additional clinical findings. Laboratory testing showed normal serum levels of alpha-fetoprotein and carcinoembryonic antigen (CEA), and high levels of lactate dehydrogenase (LDH) (375 U/L) and beta-human chorionic gonadotrophin (B-hCG) (1.9 mU/mL). The testicular ultrasound showed a multiple hypo-echoic area suspected to be a testicular tumor. The computed tomography (CT) scan was negative for metastatic lesions.
The patient underwent a right radical orchiectomy for the testicular mass; histological examination was compatible with pure seminoma. The tumor was completely resected, margins were negative, and the funiculus was free of neoplasia. The tumor was classified as pT2, N0, MX, stage I. The absence of lymph node involvement or distant metastases and the normalization of B-hCG after surgery suggested an active surveillance approach.
During the follow up, in September 2016, the patient was in a well condition when he suddenly developed an inguinal mass without associated symptoms (no pain, no urological symptoms). The CT showed an inguinal-scrotal mass 15 × 7 cm in size, which was suspected as recurrence of the tumor; no additional suspected lesions were reported. Serum levels of alpha-fetoprotein, CEA, and B-hCG were in the normal range, whereas LDH was slightly elevated from the normal range (260 U/L). Thus, the patient underwent removal of the lesion and histological examination revealed a high-grade unclassified soft tissue sarcoma with spindle cells. The patient was then referred to the Sarcoma Study Group of our institution and, in consideration of the oncological history, a revision of the previous histological exams was performed. The comparison between the two histological samples demonstrated that the primary testicular neoplasm was a rare case of mixed GCT composed of a seminomatous and a teratomatous component. A high-grade malignant mesenchymal neoplasm with spindle cells was also found to be present, which probably originated from a malignant somatic transformation of the teratomatous component ().
The primary testicular tumor, a germinal tumor with prevalent seminoma component admixed with a spindle cell sarcoma component, is a somatic transformation of a pre-existent immature teratoma. The seminoma component was immunoreactive for CD117 and OCT3/4. The sarcoma component was negative for OCT3/4, as a demonstration of the somatic type malignancy. The spindle cell sarcoma was negative for wide-spectrum cytokeratins, MDM2, smooth muscle actin, S-100, and SOX-10, with the immunoprofile of a fibrosarcoma. The coexistence of a pure seminoma component with the somatic type sarcoma was quite peculiar. The microscopic morphology of the recurring inguinal lesion was the testicular high-grade sarcomatous component of the first testicular mass, according to the hypothesis that the inguinal lesion was a recurrence of the mesenchymal component (). The histology of the groin metastasis resembled completely the features and the immunoprofile of the primary sarcoma component.
In December 2016, the patient underwent imaging with CT- and FDG-Positron Emission Tomography (PET) for suspicion of a new relapse. The FDG-PET scan showed high glucose uptake in multiple iliac adenopathies [max standardized uptake value (SUV) = 4.4; ]. A CT scan was performed 1 month after surgery, which showed a liquid mass 6.7 cm in diameter in the right inguinal cavity and multiple bilateral iliac adenopathies (). Considering the metastatic stage of the disease, the patient was directed to receive systemic therapy. The choice of the treatment protocol was driven by the sarcomatous histology; first-line treatment with epirubicin and ifosfamide was performed from December 2016 to February 2017. The subsequent abdominal-chest CT scan revaluation showed a substantial stabilization of the disease; however, FDG-PET revealed only a mild reduction in size and in glucose-uptake of the multiple iliac adenopathies (SUV max 3.7 vs. 4.4; ). In consideration of the not-entirely satisfactory response to chemotherapy oriented by the exclusive presence of sarcomatous cells, we decided to switch toward a GCT-oriented therapy. Thus, from March to June 2017, the patient was treated with a total of four cycles of BEP therapy (Bleomicin, Etoposide, Cisplatin), with good tolerance. An early revaluation of the disease by FDG-PET after two cycles of therapy revealed a complete response of the disease with total disappearance of the previous uptakes (). A complete response was then confirmed by CT-PET () and a chest-abdominal CT scan (), which was performed after the end of the treatment. The patient started a surveillance program with a CT scan and CT-PET every 4 months. He remains disease-free at last follow-up visit, 40 months after complete remission, and tumoral markers have remained negative. A timeline with the relevant data of this patient is shown in .
Given these clinical findings, we decided to characterize both the primary tumor and the recurrence in the sarcoma with whole transcriptome sequencing (RNA-seq) and exome sequencing to explore the molecular backgrounds and to further investigate any correlation with clinical course and response.
RNA-seq was done on Nextseq500 Illumina platform. RNA was extracted from the manually macrodissected tumor tissue from the FFPE slides using RecoverAll Total Nucleic Acid Isolation Kit (Thermo Fisher Scientific). Tumor tissue enrichment was at least 70%. cDNA libraries were obtained using TruSeq RNA Exome kit (Illumina), following the manufacturer's instructions. Paired-end reads were mapped on the human Reference Genome hg38 with the alignment algorithm STAR. Transcript abundance was quantified with the Python package Htseq-count and normalized as counts per million (cpm) adopting the R-bioconductor package edgeR.
Primary tumor and TMT expression profiles were compared with transcriptome data of testicular GCTs and sarcoma publicly available in The Cancer Genome Atlas project (TCGA). In particular, as testicular neoplasm, we included the subset of 94 tumors with labels “Germ Cell Neoplasms” as Disease Type, “Testis” as Primary Site and “Seminoma” or “Mixed germ cell tumor” as Primary Diagnosis (66 and 28 samples, respectively); as sarcoma, we included 259 samples with the label “Soft tissue tumors and sarcoma” as Disease Type. The principal component analysis of seminoma, mixed GCTs, and sarcoma (from TCGA) and our primary tumor and recurrece samples was performed adopting the R package prcomp. The results showed that the expression profile of sarcoma cases was distinctly separate from testicular tumors, which, in turn, are grouped in seminoma and mixed GCTs. Moreover, including our case, the analysis highlighted that the primary testicular tumor is closer to a mixed GCT and that the TMT is more similar to sarcoma (). These observations, which clearly agree with the histological diagnosis, suggested that the complete response of TMT after the PEB protocol cannot be explained by the global expression profile itself. It is reasonable to hypothesize that specific gene signatures or expression patterns could be related to chemosensitivity; however, unfortunately, we are not able to perform additional statistical analysis on a single patient.
For a more in-depth view we also performed targeted exome sequencing with the aim to study genetic alterations in both the primary and TMT in sarcoma samples. Targeted sequencing and data analysis were performed by the Foundation One CDx test, according the standard procedures of the Service. The test detects substitutions, indels, and copy number alterations (CNAs) in 324 genes, and gene rearrangements in 34 selected genes. The results revealed very few mutational events () that were shared between the diagnosis and relapse samples. Concordantly, the tumor mutational burden (TMB) was low (3–4 mutations/Mb), and microsatellite status was stable. The most relevant events were the amplification of 12p12.1, overlapping KRAS, and a region at chr4q12, encompassing KIT, PDGFRA, and KDR genes. All the other mutational events shared between the two samples were variants of unknown significance (VUS). The only novel acquisition of the sarcomatous relapse was a rearrangement of NF1 at exon 54. These results confirm the genomic stability of the tumor, which was maintained in the TMT relapse.


A 6-year-old, Norwegian born, intact male Russian Tsvetnaya Bolonka, 6 kg, was referred to the Norwegian University of Life Sciences (NMBU) at the Small Animal Teaching Hospital with a 4.5-months history of progressive weakness. Starting with weakness of the tail and reduced general condition, the clinical signs progressed to include dysphonia, muscle pain, and lameness of the pelvic limbs, more prominent on the right. Two months prior to referral, magnetic resonance imaging (MRI) and computed tomography (CT) of the lumbar region had been performed, demonstrating asymmetrical pelvic limb muscle atrophy involving particularly the right iliopsoas and quadriceps musculature. Several years before the first clinical signs of the progressive weakness appeared the dog was diagnosed with hypothyroidism and had been treated with substitution therapy since then. He had never left Norway.
General physical examination revealed reduced muscle mass of the proximal muscles of the right pelvic limb and the dog was afebrile (38.8 °C). On neurologic examination, the dog was ambulatory but paraparetic, more pronounced on the right, with an obvious hypoflexion of the hip joint, bunny-hopping gait, and a paretic tail. Cranial nerves were normal except for the observed dysphonia, whereas postural reactions were decreased in both pelvic limbs with reduced spinal reflexes in the right pelvic limb. The neuroanatomic localisation was considered to be the neuromuscular system. Differential diagnoses included inflammatory, as well as non-inflammatory, myopathies/neuropathies.
A complete blood count (CBC) and serum biochemistry profile revealed mildly increased creatinine phosphokinase, but was otherwise unremarkable. Toxoplasma gondii-specific IgM titre was border line (1:32) while IgG was negative, as was a follow-up IgM titre. Neospora caninum antibody titres were negative, and serum total thyroxine concentration was within the reference range.
By the time of a planned revisit to NMBU for laryngeal inspection, diagnostic imaging, electrodiagnostics, and biopsies 2 weeks after referral, the clinical signs had progressed further and the dog was now showing general paresis in all four limbs. During a light plane of anaesthesia, laryngeal inspection was performed showing immobile arytenoids and vocal cords bilaterally, indicative of a laryngeal paresis causing the dysphonia. Pre- and post-contrast CT examinations of the whole body were performed under general anaesthesia in dorsal recumbency. Iohexol (Omnipaque 300 mgI/mL, GE Healthcare AS, Oslo, Norway) dosed at 600 mg iodine/kg was administrated intravenously and CT images were acquired using a 4-detector row CT scanner (BrightSpeed, GE Healthcare), 1.25 mm slice thickness, 0.625 mm overlap, using helical acquisition in bone and soft tissue algorithms. The CT-examination revealed bilateral muscle atrophy with various degrees of fat infiltration evident in the muscles of the thigh, thoracic limbs, and head. The muscle atrophy was most prominent on the right side of the back (Fig. ), right pelvic limb, and right aspect of the head (temporal and masseter muscles). Changes in the triceps musculature were most prominent on the left side. Electromyography performed under general anaesthesia showed spontaneous activity in multiple muscle groups. Motor nerve conduction velocity was measured to be 40.5 m per second (m/s) (mean ± SEM in healthy dogs: 60 ± 1.1 m/s []) in the ulnar nerve, and no other nerves were tested. Muscle biopsies were taken from the right biceps femoris muscle, the left triceps muscle, and the longissimus dorsi muscles bilaterally, and submitted for a routine muscle biopsy panel established at the Neuropathology Laboratory, Ludwig-Maximilians-Universität, München, Germany. On histological examination, all muscle samples revealed multifocal interstitial and occasionally fibre-directed lymphohistiocytic infiltrates which, in some fields, were accompanied by granulomatous changes with giant cells and/or epithelioid macrophages (Fig. ). Intramuscular nerve branches were diffusely affected by endoneurial granulomatous changes. Perimysium and endomysium showed moderately increased amounts of fibrocollagenous tissue accompanied by patchy areas of mild perimysial lipomatosis. Grocott’s methenamine silver stain for fungi, Fite Faraco stain for acid-fast bacteria and Gram stain were all negative. Likewise, 16s rRNA polymerase chain reaction was negative for bacterial sequences. Based on these findings, aseptic granulomatous polymyositis and neuritis were diagnosed.
Following the negative microbial investigations, treatment was initiated with glucocorticoids (prednisolone) 1.7 mg/kg per os (p.o) twice daily for 2 weeks, followed by gradual tapering to a lower maintenance dose. At a revisit 1 month later, clinical signs had improved but were still present. Gradual improvement of the clinical signs continued over the next few months and then stabilised. At this point, neurologic examination revealed mild reductions of the right pelvic limb flexor reflex and the patellar reflex. Gait evaluation showed circumduction of the right pelvic limb but was otherwise normal. There were no signs of dysphonia or laryngeal paralysis and the tail had regained its normal position. Approximately 1 year after initiating treatment the dog had a mild relapse of clinical signs while receiving prednisolone at a dose of 0.75 mg/kg every third day. Following a dose increase, the owner reported an immediate positive response. The dog was re-examined again 16 months after initiating treatment. Gait evaluation was normal except for a mild gait disturbance of the right pelvic limb. Electromyography was repeated and spontaneous activity was still observed in several muscle groups, but to a lesser extent than before. Motor nerve conduction velocity of the right ulnar nerve was measured to be 48.0 m/s. A CT was performed and revealed similar findings as previously, except for an increased amount of subcutaneous fat, predominantly of the dorsum, considered most likely to represent an adverse effect of prednisolone treatment.
Two years after the first visit, the dog presented to the Emergency Service at NMBU with clinical signs of lethargy, pyrexia (40.2 °C), weakness, and coughing. Blood analysis, ultrasound, and CT were in agreement with a septic condition and the dog was treated accordingly. However, three days later the dog went into cardiac arrest and died. Autopsy was performed at the pathology department of NMBU and further muscle/nerve samples were sent to the Neuropathology Laboratory, Ludwig-Maximilians-Universität, München, for follow-up. The autopsy revealed purulent myocarditis, fibrinous pericarditis, interstitial nephritis, and centrilobular necrosis and thrombosis of the liver. Several muscle samples showed changes corresponding to a multifocal, subacute suppurative myositis with fibre necrosis. Muscle atrophy and intermediate neuropathy featuring axonal atrophy and partial demyelination were also present. No granulomatous changes were seen at that stage. Adipose tissue in between the muscle fibres had increased, which is expected when inflammatory changes is restricted to the interstitial compartments (Fig. ). Microbiology samples taken from the liver and spleen showed moderate growth of Escherichia coli, confirming the final septic condition.


Patient 1: A 40-year-old male patient with ESRD was experiencing secondary chronic hypertension. The patient routinely took propranolol and minoxidil for his heart issues. At the time of treatment, he was on dialysis for the last eight years. He arrived at the FMT-HVD presented with three cutaneous ATL lesions, one on an upper limb (UL), and two on the lower limbs (LL). During admission, the lesions had already evolved for 15 days and ranged from 1.5 to 4 cm in diameter (A-C). Initially, pentamidine was administered intramuscularly (IM) at a dose of 4 mg/kg, in a series of three sessions with an interval of seven days between each session, and administered on D1, D8, and D15. On D48, lesions were still present and a new series of three sessions was administered (D48, D55, D62). The lesions completely healed by D74. In the first treatment series, an episode of vomiting occurred 2 h after one of the doses of pentamidine, although it was the only adverse effect noted upon the use of this medication.
In the examinations performed on D28, creatinine was found to be 6.8 mg/dL (normal limit: 0.6-1.3 mg/dL) and post-dialysis urea was 61 mg/dL (normal limits: 15-40 mg/dL). The average level of creatinine and urea post-dialysis, during the 8 years prior to treatment with pentamidine, were 10.63 and 60 mg/dL, respectively. In 2003, after treatment with pentamidine, the levels of creatinine and urea were 9.48 and 67.08 mg/dL, respectively. The results of the examinations performed after the second series of treatment for creatinine and urea were 9 and 126 mg/dL, respectively. Mean creatinine level was stable at 9.48 mg/dL. Complete blood count, glycemia, GOT (glutamic oxalacetic transaminase enzyme), TGP (glutamic-pyruvic transaminase enzyme) and amylase did not exhibit any alterations.
The patient was monitored for six months regularly until all the cutaneous lesions healed (B). He is still on hemodialysis and exhibits similar laboratory results for creatinine and urea compared to the time before the administration of pentamidine.


Patient 2: A 60-year-old male with end-stage renal disease presented at FMT-HVD after a snakebite. He had been on dialysis for five years at the time of initiation of the treatment, and had an ulcerated lesion, which was 3 cm in diameter that erupted 30 days before he attended the leishmaniasis clinic (C). This patient was treated with pentamidine at a dose of 4 mg/kg (IM) in three series with seven-day intervals. Doses were administered on days D1, D8, and D15. No side effects were reported. In the examinations performed on D14, the levels of creatinine and post-dialysis were 11.8 and 69 mg/dL, respectively. Except amylase (122 U/L; normal: 0-95 U/L), complete blood count (CBC), glycemia, GOT, and TGP did not exhibit any alterations. During 2004, the mean levels of creatinine and post-dialysis urea were 12.44 and 64 mg/dL, respectively. These values are considered to be within the usual range for patients undergoing dialysis. After six months of follow-up, the lesions healed completely.


Extravasation occurred during the first cycle of treatment in a 70-year-old male patient, previously operated for small intestine neuro-endocrine tumors, with several metastatic lesions in the liver, bone lesions, and one subclavicular lymph node, all expressing somatostatin receptors on 111In-pentreotide scintigraphy. Nephroprotective amino acids solution was perfused intravenously in the right arm from 10:40 without any incident. Lutathera was injected in the left median cubital vein at 11:40 (T0). The routine injection protocol was used, using a pump, pushing the saline solution in the vial containing the 177Lu-DOTATATE, which was pushed in a second manifold to the vein of the patient, by the pressure increase in the vial. The flow was set to 100 mL/h, and then increased to 200 and 300 mL/h. At the end of the infusion at 12:40, the nurse noticed a swelling just over the left elbow. The patient did not complain of any pain. The nurse immediately stopped the infusion and informed the nuclear physician, who confirmed the extravasation. The medical physicist and the local referee for nuclear and radiological incidents were informed. The residual activity of Lutathera in the vial was measured using a dose calibrator, calibrated for 177Lu (MEDI 405®, Veenstra).
Osmogel® dressings were placed on the injection site. The patient underwent several whole body and SPECT/CT images. The local procedure relying on national guidelines for radiopharmaceutical extravasation was followed []. Adapted interventions were used to stimulate the lymphatic elimination during several hours after the detection of the extravasation, including in the night: warming and elevation of the left arm and repeated self-massaging.


The proband (V-1) () is a 7-month-old female who presented to clinic with greater than 6 months of mild anterior and posterior cervical and axillary lymphadenopathy, with the largest lymph node measuring 1 cm in diameter in the neck. She also had a spleen of 7.5 cm in length, slightly larger than normal for age, with the upper limit being 7 cm in length for a 12-month old (). She had a history of asthma triggered by viral respiratory tract infections and no history of recurrent or severe bacterial sinopulmonary infections. She was normal developmentally for her age. Complete blood count (CBC) with differential was normal at presentation, but at 2 years of age she experienced an episode of autoimmune hemolytic anemia, with hemoglobin nadir of 5.3 g/dL and mild thrombocytopenia (platelets 108,000). Immune evaluation was notable for normal immunoglobulin levels and normal diphtheria and tetanus antibody titers; however, pneumococcal titers were only protective for 50% of a 10-serotype panel, and patient had a low Haemophilus influenzae type B (Hib) titer ().
Her mother (IV-1 in ) reported a personal history of splenomegaly, which had been diagnosed along with “kidney enlargement” during her pregnancy, and a family history of splenomegaly, lymphadenopathy, and hematologic malignancy in prior generation maternal relatives. The grandmother of subject IV-1, subject II-2, reported a personal history of neck lymphadenopathy requiring excision during her late teenage years. Subject II-2 suspected that she had inherited her tendency toward lymphadenopathy from her father (I-1 in ), whose sister had died of leukemia at age 17.
Among living family members with suspected ALPS, a 17-month-old male second cousin (V-2) was also seen in the clinic for persistent lymphadenopathy. Subject V-2 had posterior cervical lymphadenopathy, splenomegaly, and history of thrombocytopenia. There was no history of recurrent or severe infections, bleeding, or other illnesses. His mother (IV-2) reported a personal history of recurrent lymphadenopathy, splenomegaly since childhood, and chronic anemia with no formal history or testing for ALPS. Subject IV-1 and IV-2 (mothers to proband and V-2, respectively) share a maternal grandmother (II-2), who reported neck lymphadenopathy in her teenage years, as mentioned previously. This maternal grandmother (II-2) had a sister (II-1) who was healthy, and a brother (II-3) who required splenectomy at age 15 and often had abnormal blood cell counts in childhood. A child of II-1, (male child III-1), was healthy. II-3 had a son, III-6, who was healthy, but his grandson IV-3 required splenectomy at 1 year of age due to splenomegaly. Subject II-2 also had four children (subjects III-2, III-3, III-4, and III-5) who did not show notable signs of ALPS. Based upon this information, further evaluation was pursued in available family members, which included two half-siblings of subject V-2: subjects V-3 and V-4. Subject V-3, a 6-year-old female, had a history of recurrent oral lesions resembling herpes simplex virus with no clinical evidence of ALPS. Subject, V-4, an 8-year-old female, had a history of recurrent ear infections and otherwise no clinical history suggestive of ALPS.


A 60 years old male infected with SARS-CoV-2 virus, confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) test, was referred to our center on July 25, 2020, with the diagnosis of severe COVID-19 disease with moderate acute respiratory distress syndrome (ARDS) for which he was hospitalized elsewhere for six days. He had a history of nonproductive cough and fever (recorded up to 101°F) for six days. He developed shortness of breath and worsening cough two days before presentation to Tribhuvan University Teaching Hospital, Kathmandu (TUTH). On physical examination upon arrival, he was found dyspneic with respiratory rate of 28/min, SpO2 of 93% with 40% O2 via venturi mask. On admission, his body temperature was 98°F, with pulse rate 90/minute, and blood pressure 150/90 mmHg (MAP = 109 mmHg).
The patient was obese (body mass index 35 Kg/m2) with multiple comorbidities: systemic hypertension for which he was taking Amlodipine + Losartan (2.5 mg + 50 mg), type 2 DM for which he was taking Metformin, and psoriasis for which he was on and off on steroids and recently took Methotrexate (last dose taken two weeks before presentation).
On the day of admission (day 0), the patient was kept on high-flow nasal cannula (HFNC) with oxygen flow maintained at 60 Liters/min and FiO2 titrated to target SpO2 >88%. That day, his oxygen requirement via HFNC increased from 40% to 60%. He was on restrictive fluid intake (targeting a negative fluid balance) and advised to lie down in prone position as much as possible. His laboratory parameters were all normal except decreased lymphocytes and elevated levels of liver alanine transaminase (ALT), serum urea, and urine albumin (Table ). His medications included the following: injection Dexamethasone 6 mg q24h intravenous (IV), tablet Aspirin, Inj. Enoxaparin 80 mg SC q24h, Paracetamol for fever, and antihypertensive drugs continued. Metformin was stopped and switched to a regular insulin sliding scale. Despite these medications, he was restless with increased shortness of breath, tachypnoea (RR up to 28/minute), and increasing oxygen requirement. On day 1, the patient was given Inj. Remdesivir 200 mg stat followed by Inj. 100 mg q24h (Figure ). His total leukocyte count increased on day 2 onward, along with increased C-reactive protein (CRP), serum ferritin, and ALT levels (Table ).
Despite the first doses of two repurposed drugs, his oxygen requirement kept increasing up to 90% via HFNC. On day 3, Inj. Aztreonam was added empirically for suspected secondary bacterial pneumonia. It was selected among several other available antibiotics for its safety profile. In the background of worsening hypoxemia, increasing bilateral infiltrates on chest X-ray, and elevated total leucocyte counts, there was a strong suspicion of secondary bacterial infection, particularly staphylococcal infection which is one of the most common lower respiratory tract gram-positive bacterial infections reported among aging population in our center (Figure , Table ). Accordingly, Inj. Teicoplanin was added empirically while awaiting blood culture report (which came out negative) and sputum gram stain and culture results (later reported to have pus cells and fungal growth).
Although the patient was gradually feeling better on day 4 with decreased cough, decreased shortness of breath, and normal respiratory rate, he still had high oxygen requirement, with bilateral chest X-ray infiltrates, and elevated inflammatory biomarkers reported on day 5 (CRP, serum ferritin, procalcitonin, D-dimer) (Figure , Table ). The treating physicians then decided to transfuse plasma to the patient. Convalescent plasma was obtained from a blood group matched (B+) healthy donor—who recovered from SARS-CoV-2 infection, was asymptomatic for 26 days, had negative RT-PCR report on July 04 (26 days before plasma collection), and gained high titer (IgG S/Co 421; neutralization antibody titer >1:250) estimated by Chemiluminescence Immunoassay Analyzer (CLIA) method in Vitros5600, Ortho clinical diagnostic machine. 200 mL of donor's plasma was successfully administered to the patient over 2 hours on day 6 of admission (July 31, 2020), that is, 12 days after onset of the patient's symptoms. No adverse effect of the intervention was reported.
The patient's oxygen requirement decreased gradually after convalescent plasma transfusion. His laboratory parameters improved on day 7: normal D-dimer, decreased levels of CRP, serum ferritin, and procalcitonin (Table ). On day 8, his oxygen saturation level was above 88% at 4 L/minute oxygen via nasal prongs, so his HFNC was discontinued. His chest X-ray gradually improved (Figure ). The patient was shifted from critical care to the general ward on day 9 of his admission, that is, after 15 days of symptom onset, on oxygen at 3 L/min via nasal prongs. On the same day, the patient was transferred to another hospital on his personal wish for rehabilitation measures as part of ongoing treatment. During virtual and in-person follow-ups with the treating physicians in the following days, the patient was reported fully recovered.


A 49-year old man, diagnosed with PD in 2014, self-reported excessive generosity following an increase of ropinirole in the previous year. At the time of the consultation, he was on a regime of ropinirole 8 mg bid (total daily dose/TDD 16 mg) and L-dopa 200 mg tds (TDD 600 mg), not suffering from any motor or non-motor fluctuations. He had started to support three asylum seekers, helping them with administrative issues, letting one of them live in his house, and giving them money (equivalent to more than 15′000 CHF). He felt deep compassion for the three men and did not want to stop his generosity despite his limited financial resources. As a consequence, he borrowed money from his parents and overdrew his bank accounts. The year before, he had to leave his job after 33 years due to gross misconduct related to risky behavior, and his wife left him. In addition to excessive generosity, he also reported episodes of binge eating and a new-found interest in creative hobbies. His libido had increased and he started seeking sexual encounters with men for the first time in his life. He had sexual intercourse with one of the asylum seekers occasionally, but stated that he never paid him for sexual favors and that the man did not seem to exchange sexual favors in the hope for financial support. No depressive symptoms or anxiety were reported. He met the criteria for hypomania, but not for mania according to DSM-5. He consented to a reduction of ropinirole from 16 mg/day to 4 mg bid (TDD 8 mg) and an increase of L-dopa to 700 mg TDD (administered in shorter intervals and distributed in four doses). Two months later he reported a decrease in generous behavior, libido and hypomania, experiencing no depressive symptoms or apathy.


A 47-year old man, diagnosed with PD in 2017, developed several ICDs and reckless generosity under pramipexole 2.25 mg od, which had been reduced to 1.5 mg od before the neuropsychiatric assessment. He experienced no motor fluctuations. He worked as a taxi driver and had started to drive customers around for free, lending money to them occasionally, equivalent to several thousand Swiss francs at a time in some cases. He reported that he did not want to lend them money, but that he felt compassion for the people and that he simply could not decline their requests. He described that his character had changed from being shy and insecure to being self-confident, jovial, and extroverted. He had started speculating on the stock market and had lost over 27′000 CHF within a couple of months. He had overdraws of over 3′000 CHF and had borrowed money from his brother. His libido had increased; he reported having more sexual fantasies, consuming pornography regularly, and starting to visit prostitutes. He stated that his generosity was not linked to his sexual encounters. At the time of consultation, he reported no anxious or depressive symptoms. He met the criteria for hypomania, but not for full-blown mania according to DSM-5. After pramipexole was substituted with L-dopa 100 mg tds (TDD 300 mg), his motor state remained stable and his excessive generosity, speculation on the stock market, hypersexuality and hypomania gradually remitted, without showing any depressive symptoms or apathy.


A 56-year old male, diagnosed with PD in 2011, was referred to our clinic to evaluate the possibility of deep brain stimulation (DBS). At the time of the first neuropsychiatric assessment, he was on a regimen of L-dopa/carbidopa/entacapone 675/168.5/1000 mg distributed in five doses and safinamide 100 mg od, and experienced wearing off with prolonged OFF-phases. He had developed reckless generosity under ropinirole 8 mg od, which persisted for another 5 months after ropinirole had been discontinued in 2018. Over 4 years, he had given an estimated 2.9 million CHF to his medical massage therapist, who had repeatedly besieged him to give her money. He stated that he felt very sorry for the massage therapist, as she told him that she would be financially ruined without his support. Later, when she started to pressure him by sending him multiple texts a day asking for money, he felt like he had to continue to support her despite not wanting to, to somehow get his money back in the end. He felt embarrassed about the situation and was hiding it from his wife. He never had an intimate relationship with the massage therapist and said that he was never interested in any sexual favors from her. His behavior felt inexplicable to himself, as he had built up a successful business in the past, never experiencing any financial trouble before. He had taken up several credits, borrowed money from friends, and had also started to access accounts from his company. At the time of the neuropsychiatric assessment, the debt enforcement office had announced that they would evict him and his wife from their apartment in the next few days. He was devastated, showing symptoms of anxiety and depression. However, he described that until he had stopped ropinirole, his mood had been elevated and that he had been a passionate racing driver. Despite a slightly increased libido in the relationship with his wife, he had not experienced any other ICDs. One year after the initial consultation, he reported that his financial situation had improved, although he still had some tax debts. He had taken legal action against the massage therapist and had managed to stay in his house. The reactive depressive symptoms and anxiety had improved, but not fully remitted, and he had gradually developed apathy. He received DBS 1.5 years after his initial consultation. His motor symptoms, depressive symptoms, anxiety, and apathy improved under DBS. On one occasion he lent 1000 CHF to an acquaintance, again after being pressured to do so. Other than that he reported no relapse.


A 50-year-old man with acute onset of dyspnea visited another hospital. He had an unremarkable medical history. However, he had smoked two packets of cigarettes per day for 25 years and had been in the construction industry with significant asbestos exposure since he was 20 years old. Chest radiography showed extensive abnormal shadows in the right lower lung field and cardiac expansion (Figure ). Chest computed tomography (CT) revealed moderate right pleural effusion, two pleural nodules, and a large mediastinal tumor invading the pericardium (Figure ). Aside from the mediastinal tumor and pleural nodules, no further abnormal fluorodeoxyglucose uptakes were detected by positron emission tomography CT (Figure ). The pleural effusion was drained. The cell block sample showed some multinucleated and atypical mesothelial cells with hump-like cytoplasmic processes among lymphocyte inflammation upon hematoxylin–eosin (HE) staining (Figure ). On immunohistochemistry (IHC) staining, calretinin, D2-40, WT-1, and HEG1 were positive (Figure ) while TTF-1, CEA, claudin-4, and desmin were negative. Based on these findings, MPM was suspected. The patient was then referred to our hospital.
The patient was urgently hospitalized because of severe tachycardia and hypoxia at his initial visit. Laboratory findings, including tumor markers, such as CEA, CYFRA, and ProGRP, were almost within normal limits, except for high levels of D-dimer (1.2 × 104 ng/ml) and CRP (0.15 g/l). Transthoracic echocardiography showed that both ventricles were pushed directly by the tumor and had almost collapsed.
A diagnostic percutaneous needle biopsy was performed. Polymorphic variant cells with nonspecific differentiation were observed and almost all markers, including calretinin, D2-40, and WT-1, were negative. The histological findings of the mediastinal tumor were completely different from those of pleural effusion. This did not lead to a definitive diagnosis of MPM. After a few days, the patient died of untreated cardiac tamponade. An autopsy revealed that atypical fibroblast-like cells were arranged in a storiform pattern. This was associated with a pleomorphic feature (Figure ). Immunohistochemically, tumor cells were negative for almost all markers such as CK-AE1/AE3, CK-CAM5.2, EMA, calretinin, desmin, α-SMA, D2-40, CD34, S-100, and neurofilament. This finding was similar to the needle biopsy sample. Thus, we diagnosed the patient with UPS.


A 65-year-old male patient presented to our hospital with a history of a cough and hip joint pain. Computed tomography (CT) revealed a mass lesion in the left upper lung lobe and a large mass in the left pelvis. Radiographic and pathological evaluations of the biopsy samples from the left lung and pelvic tumors led to a diagnosis of advanced SC with bone metastasis (cT4N0M1c, cStage IVB, UICC version 8). Immunohistochemistry (IHC) analysis of the biopsy sample from the lung tumor demonstrated 1% PD-L1 expression on tumor cells (clone 22C3, Dako) (Figure ), and no druggable driver mutations were observed.
The patient received four cycles of pembrolizumab (200 mg/bodyweight) with CBDCA (AUC 5) plus PEM (500 mg/m2) after palliative local radiotherapy (40 Gy/20 Fr.) to his left pelvis. The tumor in the left lung shrunk significantly and the left pelvic bone metastasis underwent ossification after four cycles of treatment (Figure ). However, treatment was discontinued because the patient developed pneumonitis and colitis which were considered to be severe immune-related adverse events (iRAEs) (Figure ). The patient commenced immunosuppressive treatment with 60 mg of prednisolone 38 days after the initiation of the fourth cycle of treatment. His pneumonitis and colitis fortunately improved; however, the tumor in his left lung had a significant regrowth 84 days after the initiation of prednisolone (Figure ), whereas the site of bone metastasis was stable, probably due to prior irradiation. After the iRAEs had subsided, the patient received docetaxel (60 mg/m2) plus ramucirumab (10 mg/kg) as second-line treatment because the tumor size had evidently increased in size at that point. However, the mass in the left lung significantly increased after two cycles of docetaxel plus ramucirumab treatment (an increase in diameter from 93 mm before treatment to 125 mm after treatment). The patient chose not to receive third-line therapy and continued with best supportive care due to a decrease in performance status.
IHC review of the biopsy samples from the left lung and pelvic tumor at the time of diagnosis showed that there were few TILs including CD8+ T cells (NCL-L-CD8-4B11, Leica Microsystems), CD4+ T cells (NCL-L-CD4-1F6, Leica Microsystems), and PD-1+ cells (NAT105, Abcam) in both biopsy samples obtained from the primary lung cancer site and metastatic site of the left pelvis (Figure ).
Written informed consent for the publication of this case report was obtained from the patient. This case study was approved by the Institution Review Board of the ethics committee of our institution (Approval #20122147).


A 51-year-old woman was seen in consultation for right arm discomfort and edema (Fig. ). She had a past medical history of multiple bronchiectasis infections in context of congenital ectodermal dysplasia. Recurrent sepsis led to acute kidney injuries and eventually to anuric ESRD. She required hemodialysis 3 times a week, currently through using a right radiocephalic arteriovenous (AV) fistula, for almost 25 years. A renal transplant had failed immediately, 15 years prior. She had a right brachiocephalic vein stenosis, previously stented, and a suspicion of breast calciphylaxis diagnosed 3 years earlier. Her weight was 36 kg (BMI of 12) and she had negligible subcutaneous fat.
A right upper extremity ultrasound revealed a segmental nonocclusive thrombus in the lower part of the right internal jugular vein (IJV). She then had an angiogram and was diagnosed with a severe brachiocephalic vein in-stent stenosis and a moderate stenosis along the juxta-anastomotic cephalic vein fistula. Balloon dilatations of both stenosis were done but the intervention on the stent was complicated by a small focal contained rupture, which was again balloon dilated to ensure hemostasis. Soon after the intervention, the patient was seen at the thrombosis clinic. She reported improvement of her right arm symptoms and the initially described right nonocclusive IJV thrombosis was thought to be chronic. Surveillance by repeat ultrasound 1 week later without anticoagulation was chosen as initial management.
The next ultrasound reported interval progression of the known thrombus in the IJV (now occlusive) and nonocclusive extension into the subclavian vein. The stent was still patent. The patient was reporting worsening pain and swelling over the right side of her neck and her right arm for the last week. As such we diagnosed an acute right upper extremity deep vein thrombosis, most likely provoked by the initial flow disturbance caused by the in-stent stenosis and thereafter by the angiographic intervention.
She was treated as an outpatient with apixaban 2.5 mg twice daily for 6 weeks. Apixaban was taken at 10 am and 10 pm, while dialysis treatments were scheduled at 6 pm. At her 1 week follow up visit, the pain and swelling were improved. Over 4 weeks, apixaban anti-Xa levels were measured on dialysis days 8 h (i.e. 6 pm, before dialysis) and 12 h after the morning dose (i.e. trough levels, obtained at 10 pm, after dialysis and before the next dose). Anti-Xa were obtained using a CS-2000i (Siemens) analyzer with Innovance heparin reagent (Siemens) and calibrated by a STA®-Apixaban Calibrator kit (Diagnostica Stago, working range: 20–500 ng/mL). Surveillance ultrasound done 1 and 5 weeks after treatment initiation revealed stability of the upper extremity deep vein thrombosis and patency of the stent.
Over 4 weeks, the anti-Xa trough levels ranged from 58 to 84 ng/mL, while levels obtained before dialysis, i.e. 8 h after the morning dose, were 92–135 ng/mL. Monitoring was not continued up to the end of the treatment considering there was no trend of anti-Xa levels to increase overtime. There was no concomitant medication with significant apixaban interactions and liver function was normal. These range of anti-Xa levels are similar to what would be expected as a trough level in patients with preserved renal function. There were no adverse events in the 3 months after anticoagulation initiation.


A 53-year-old postmenopausal Iranian woman presented to the hospital for a progressively growing painful cesarean scar mass. Her personal history included three previous Pfannenstiel cesarean sections without any medical diseases. The last cesarean section was performed 23 years earlier. Pfannenstiel scars were adjacent to her pubic symphysis. She had no family history of gynecological malignancy. She previously had bloody discharge during her menstrual cycle from a very small orifice inside the abdominal cesarean scar for 16 years. The monthly bloody discharge was stopped after her menopause. She detected a mass that was approximately 3 cm in diameter during her self-examination of her cesarean scar 3 years after menopause. The mass was converted to a huge one over 3 months (Fig. ). On physical examination, a significant large, firm, and fixed mass was observed in her suprapubic Pfannenstiel cesarean scar and extended upward to the anterior abdominal wall. An abdominopelvic computed tomography (CT) scan revealed a 9.1 × 5.6 × 4.7 cm heterogeneous solid mass with a cystic component in the lower part of the rectus muscle. The observed mass expanded to the subcutaneous tissue, with close contact with the pubic symphysis, and extended to the retropubic space. Other pelvic and abdominal organs were observed to be normal in the first imaging (Fig. ). Needle biopsy of the mass was performed under ultrasound guidance. Histology revealed an undifferentiated carcinoma. Thorax CT scan, colonoscopy, upper gastrointestinal endoscopy, mammography, and transvaginal ultrasound were all normal. The patient was scheduled for complete excision of the abdominal wall mass as determined by the cancer multidisciplinary team (MDT). A complete excision of the mass and its surrounding tissues was performed. The permanent histology revealed clear-cell carcinoma arising from the Pfannenstiel cesarean scar (Fig. ). Permanent pathological reports indicated negative excision margins; however, the tumor was very close to the surgical margin in the lower part of the mass adjacent to the pubic symphysis (1 mm).
Thirty days after the surgery, the patient initiated chemotherapy with six cycles of paclitaxel and carboplatin every 3 weeks. To follow up, an abdominopelvic ultrasound was performed 3 months after the last chemotherapy treatment. Ultrasound was normal. The patient was asymptomatic nearly 5 months after the termination of chemotherapy. However, she had abdominal discomfort later on. Positron emission tomography–computed tomography (PET-CT) was performed 5 months after the last chemotherapy treatment (Fig. ) and demonstrated ascites and recurrences in the abdominal wall, retropubic space, and pelvic peritoneum space. Therefore, she received second-line chemotherapy with four cycles of bevacizumab, cisplatin, and doxorubicin. She was resistant to the second-line chemotherapy, and the tumor progressed diffusely in the abdominopelvic space during the second-line chemotherapy course. She had severe abdominal pain and mainly presented gastrointestinal symptoms such as nausea. It was determined by the MDT that the patient was a candidate for palliative therapy. However, she refused the MDT decision and insisted on a second surgery. She had the surgery in another hospital. Her second surgery consisted of total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO), pelvic washing, excision of the abdominal wall mass, segmental resection of a narrow lumen of the large bowel, and end-to-end anastomosis and selective large pelvic lymph node dissection. All specimens showed clear-cell carcinoma involvement. The patient received third-line chemotherapy with three cycles of gemcitabine and vinorelbine. She did not return to our center after the second surgery; however, she sent us her treatment records. Unfortunately, she died 20 months after diagnosis.


A 58-year-old Iranian postmenopausal woman referred to the hospital because of a abdominal wall mass and hernia. She had a history of three cesarean sections with a midline abdominal incision. Her last cesarean section was performed 20 years earlier. Physical examination demonstrated a partially mobile and large mass in the anterior abdominal wall in the midline cesarean scar, extending bilaterally to the midclavicular line. The upper margin of the mass was adjacent to her umbilicus, where there was a large umbilical hernia above the mass (Fig. ). Pelvic ultrasound showed an irregular 12 × 8 × 8 cm mass in the abdominal wall anterior to the rectus muscle involving subcutaneous tissue, a large umbilical hernia containing omentum, and a well-defined left solid adnexal mass (4.1 × 3.7 × 5.1 cm in diameter). An abdominopelvic CT scan confirmed the ultrasound findings (Fig. ). The peritoneal surface of the anterior abdominal wall was intact, and other abdominal and pelvic organs were normal. The chest X-ray was normal.
A local incisional biopsy of the abdominal wall mass was performed before referral to our department. The histology implied clear-cell carcinoma
The patient was scheduled for surgery as determined by the MDT. Midline laparotomy was performed. The abdominal wall mass invaded the lower half of the rectus muscles. The mass reported in the left adnexa was indeed a large pelvic lymph node adjacent to the left external iliac artery. Uterus and ovaries had a normal appearance. The patient underwent a complete excision of the abdominal wall mass including the rectus muscles and fascia, peritoneal washing, resection of the enlarged pelvic lymph nodes, TAH, and BSO. Due to the large abdominal wall defect following the excision of the abdominal wall mass, reconstructive surgery was performed to repair the abdominal wall. The defect was covered with a synthetic mesh. The results of the permanent histology of the abdominal wall mass and the enlarged pelvic lymph node were similar, indicating clear-cell carcinoma (Fig. ) without any marginal involvement. The pathology results of ascites and surgical specimens were negative. Twenty days after the reconstructive surgery, the patient initiated chemotherapy with six cycles of paclitaxel and carboplatin every 3 weeks. An abdominopelvic CT scan was performed 6 months after the completion of the treatment and revealed normal findings. At present, the patient is alive without any recurrence (26 months after diagnosis). The basic characteristics of the patients, imaging results, surgical procedure, and adjuvant treatment are summarized in Table .


A 40-year-old female with a past medical history significant for asthma, chronic obstructive pulmonary disease (COPD) due to 10-pack-year smoking history, and recurrent right lower lobe (RLL) pneumonia, presented with worsening cough and fatigue. The patient reported pleuritic chest pain localized to the right lower chest but denied shortness of breath, fever, chills, weight changes, nausea, symptoms of acid reflux, or difficulty swallowing. She had three right lower lobe pneumonias during the last eight months, with the most recent occurrence being in the previous six weeks when she was treated with cefuroxime and prednisone as an outpatient. She drinks alcohol occasionally and does not ingest or inject illicit drugs. She has no pertinent family history and is up to date with immunizations, including the pneumococcal polysaccharide PPV23 vaccine.
On presentation, the patient’s vital signs were a blood pressure of 110/70 mmHg, a heart rate of 76 beats per minute, a temperature of 98.6 degrees Fahrenheit, respiratory rate of 18 breaths per minute, and oxygen saturation of 97%. The patient was in mild distress on physical exam, with an unremarkable cardiac exam. On pulmonary exam, the patient had decreased breath sounds in the right upper lobe (RUL) and RLL, and a normal left lung exam. She did not have rales; however, her exam was positive for mild wheezes in the right lower lung field. Chest X-ray showed right lower lung opacity (Figure ), and computed tomography (CT) scan of the chest revealed an obstructing nodular opacity in the right lower lobe bronchus with post-obstructive RLL consolidation (Figure ). This was confirmed with positron emission tomography (PET), which showed increased uptake in the RLL corresponding with a confluent infiltrate (Figure ). The PET scan also revealed an obstructive nodule with post-obstructive pneumonia (Figure ). Bronchoscopy revealed a large completely obstructing polypoid and vascular lesion in the right lower lobe (Figure ). Fine needle biopsy revealed a nodular aggregate of bland appearing chondroid tissue with a lobulated contour, without significant cellular pleomorphism, binucleation, or mitotic activity. This confirmed a final diagnosis of an RLL endobronchial hamartoma. The patient underwent robotic video-assisted thoracoscopic surgery (VATS) for removal of the mass and right lower lobectomy. At her five-month follow-up appointment, she reported no further symptoms.


A 28-year-old male patient with intraventricular hemorrhage and intracerebral hemorrhage in the left basal ganglia underwent extraventricular drainage and ventriculoperitoneal shunting for hydrocephalus. At 30 months after onset, he was admitted to the rehabilitation department of our university hospital. Brain magnetic resonance imaging (MRI) showed leukomalactic lesions in the hypothalamus, bilateral medial temporal lobe, and bilateral basal ganglia (Fig. A). He showed intermittent high body temperature (maximum: 39.5°C, 38.5–39.2°C). However, he did not show any signs of infection upon physical examination or in his white blood cell count and inflammatory enzyme levels including erythrocyte sedimentation and C-reactive protein. Eight age-matched normal subjects (4 male, mean age, 26.6 years; range, 21–29 years) were enrolled in this study as control subjects. The patient's father and all normal subjects has provided informed consent for publication of the case, and the local ethics committee approved the study protocol.
When he showed hyperthermia during admission, we applied four types of management including external cooling methods (tepid massage and ice pack), hydration, and medication (propacetamol 1 g, intravenous injection).[ He revealed similar pattern of hyperthermia in terms of intensity and frequency during two month's admission at our hospital.
A multi-channel head coil on a 1.5 T Philips Gyroscan Intera (Philips, Best, Netherlands) with 32 gradients was used for the acquisition of DTI data. The patient's DTI data was acquired at 30 months after stroke onset. We acquired 67 contiguous slices parallel to the anterior commissure-posterior commissure line. DTI scanning parameters were as follows: acquisition matrix = 96 × 96; reconstructed to matrix = 192 × 192; field of view = 240 mm × 240 mm; repetition time = 10,398 ms; echo time = 72 ms; parallel imaging reduction factor = 2; echo-planar imaging factor = 59; b = 1000 s/mm2; number of excitations = 1; and slice thickness = 2.5 mm. Eddy current-induced image distortions were removed by using the affine multi-scale two-dimensional registration provided in the Oxford Centre for Functional MRI of Brain Software Library. DTI-Studio software (CMRM, Johns Hopkins Medical Institute, Baltimore, MD) was used for evaluation of the hypothalamus, which was identified by locating the anterior boundary of the optic tract and the posterior boundary of the mammillary body at the level of the upper midbrain (Fig. A).[ Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) estimates were obtained for the hypothalamus. Regions of interest for the hypothalamus were localized by using the optic tract (anterior boundary), the mammillary body (posterior boundary), and the midline (medial boundary) at the level of the upper midbrain in the patient (C) and a representative normal subject.


A 56-year-old Taiwanese man presented to the neurosurgeon clinic of a university hospital for left neck soreness with numbness radiating to the left lateral shoulder for three weeks. The neck discomfort was aggravated while the neck rotated or tilted to the right. Physical examination revealed a positive Spurling test. No muscle weakness or muscular atrophy was observed. The deep tendon reflex of the left biceps tendon was recorded as 1+. Cervical spine radiography revealed spondylosis without segmental instability. Four days later, he was referred to the Physical Medicine and Rehabilitation Department for electrophysiological examination under the impression of cervical radiculopathy. Motor conduction was studied by recording abductor pollicis brevis while stimulating median nerve at wrist and elbow, and recording abductor digiti minimi while stimulating ulnar nerve at wrist and elbow. Sensory conduction was performed by recording 2nd and 5th digital nerves when stimulating the median and ulnar nerves individually. A Medelec Synergy electromyograph (Medelec Biomedical Inc., Surrey, UK) was used for signal acquisition.
Nerve conduction showed prolonged distal latency and decreased velocity (34.6 m/s) in the ulnar sensory study. Ulnar motor study was within normal range (distal latency 2.75 m/s, velocity 61.5 m/s). On median nerve study with pickup over the abductor pollicis brevis, distal latency and velocity were both within normal range, except for the drop in amplitude between stimulation at the wrist and stimulation at the below-elbow (10.5 mv / 4.9 mV), which was compatible with the conduction block pattern. Moreover, when we left the recording electrode on the abductor pollicis brevis and stimulated the ulnar nerve at the wrist and elbow, the amplitude of the abductor pollicis brevis was higher at the elbow than at the wrist. Under the suspicion of anomalous innervations between the forearm median and ulnar nerves, we checked the sensory nerve innervation using an orthodromic study. We stimulated 3rd finger and recorded the SNAP on both the wrist and elbow of the median and ulnar nerves individually. We did not record any discrepant SNAP distribution, which suggests nerve crossing over. In the electromyography study, left C5 and C6 paraspinal muscles showed increased spontaneous activity (fibrillation and positive sharp wave). In addition, increased polyphasic waves were also found in the left biceps brachii and left extensor carpi radialis. Based on the results of the electrophysiological examination, we concluded that this patient had left C5 and C6 subacute radiculopathy with active denervation and left subclinical ulnar sensory neuropathy, and verified the existence of ulnar-to-median anastomosis.


A 67-year-old male patient with past medical history of CAD, hypertension, prediabetes, obesity, and chronic back as well as hip pain presented to the emergency department after an ophthalmic procedure (Phaco and intraocular lens [IOL] implant) with asymptomatic PVCs with the intermittent occurrence of bigeminy. At the time, the patient was free of any chest pain, shortness of breath, dizziness, or lightheadedness; he had no signs or symptoms of decompensated heart failure.
His ECG showed normal sinus rhythm with the presence of fragmented QRS (fQRS) complexes in lead V2 in the absence of PVCs (Figure ). However, with the occurrence of PVCs, there was significant fragmentation of the extrasystoles seen in other coronary territories (Figure ).
Review of his most recent cardiac history revealed that this patient had a coronary angiogram in 2014 showing ostial left anterior descending (LAD) artery 50% stenosis, mid LAD 70% stenosis, first diagonal 95% stenosis and totally occluded right coronary artery (RCA). He had mid LAD stent placed at this time. In 2020, he presented with chest pain on exertion and the decision was made at that time to proceed with a myocardial perfusion nuclear imaging study which revealed 21% of the left ventricular (LV) mass was ischemic. His resting left ventricular ejection fraction (LVEF) was 34% with global hypokinesis but during stress his LVEF fell to 25% with worsening wall motion abnormality noted anteriorly with an attenuated global myocardial blood flow reserve of 1.24. In view of these results, another coronary angiogram was then performed showing a patent mid LAD stent with a distal LAD 70% stenosis, a 95% first diagonal stenosis, and a totally occluded RCA with left circumflex artery (LCX) minor irregularities. Percutaneous coronary intervention (PCI) to both distal LAD and first diagonal branch were performed resulting in resolution of symptoms and overall clinical improvement. LVEF improved after revascularization from 34% to 40% as well.


A 56-year-old woman presented with abdominal pain, bloating, early satiety, changes in bowel habits, and weight loss. Her past medical history included a ten-year history of progressive fatigue prompting early retirement at age 50 and a five-year history of left breast tenderness near her inframammary fold. She had undergone augmentation mammoplasty with subpectoral Dow Corning double lumen smooth implants 27 years previously and had never experienced a need for replacement.
An abdominal CT scan revealed splenomegaly, enlarged splenic hilar lymph nodes, and borderline-enlarged periaortic lymph nodes (). Subsequent peripheral blood analysis and flow cytometric immunophenotyping, revealed pancytopenia and a clonal B-cell population with nonspecific immunophenotype and villous morphology. Her subsequent bone marrow aspirate and core biopsy were most consistent with splenic marginal zone lymphoma, occupying approximately 20% of marrow cellularity. Immunostains were positive for CD20 and negative for Cyclin D1 (). Flow cytometry of the bone marrow showed a monoclonal B-cell population expressing CD20 (bright), CD45, FMC-7, CD19, CD11c (dim), CD22 (dim), and kappa immunoglobulin light chain restriction. The monoclonal B-cells were negative for CD5, CD10, and CD23.
A PET-CT scan demonstrated mildly hypermetabolic epigastric lymph nodes, hypermetabolic splenomegaly consistent with lymphoma, left breast increased metabolic activity suspicious for capsulitis, and bilateral findings suspicious for implant rupture. Subsequent breast MRI showed right implant intra-capsular contained rupture and left implant rupture with extracapsular silicone extension. There were two discrete 5-mm foci of extracapsular silicone along the inferior medial aspect of the left implant. Physical exam showed bilateral grade 2 Baker capsular contracture and no lymphadenopathy. The patient received weekly rituximab treatment for four weeks and also underwent bilateral capsulectomy and implant removal. Histologic examination of the excised capsular tissue demonstrated a marked inflammatory response and silicone granulomata, but no overt malignancy. On follow up eight years after therapy, the patient is currently alive without evidence of disease.


A 46-year-old man with no significant past medical history presented with blurry vision and was ultimately diagnosed with choroidal melanoma of the right eye. He underwent plaque brachytherapy and was followed with surveillance imaging. Fifteen months after his original diagnosis, MRI abdomen revealed multiple hepatic lesions. A CT-guided liver biopsy of one of the lesions was performed, and pathology confirmed metastatic uveal melanoma. Initial staging showed only liver metastases. The patient travelled to the United Kingdom and received four cycles of chemosaturation with PHP using high-dose melphalan over a 6-month period. Repeat imaging initially showed a partial response to this treatment in the liver. After 6 months, the patient started to complain of rib pain and back pain. A PET/CT scan revealed diffuse bony metastases. He was treated with palliative radiation prior to initiation of nivolumab at 3 mg/kg every two weeks.
Shortly after the first cycle of nivolumab, he began having mild right upper quadrant pain, low-grade fevers, diaphoresis, and fatigue. Two weeks later, he was given a second dose of nivolumab. Then, one week after that, his right upper quadrant abdominal pain worsened, and he was found to have an aspartate aminotransferase (AST) level of 310 U/L, alanine aminotransferase (ALT) of 187 U/L, alkaline phosphatase of 713 U/L, and total bilirubin of 3.8 mg/dL (). Clinical exam revealed marked hepatomegaly. Given his extensive liver metastases, there was an initial question about progression of his disease versus an autoimmune hepatitis, so a PET/CT scan was performed revealing an enlarged liver along with diffusely homogenous uptake in the liver. This suggested a diffuse inflammatory process involving the entire liver rather than progression of metastatic disease which would have shown more heterogeneous FDG avidity corresponding to the sites of tumor activity ().
The patient was admitted to the hospital, and further lab workup including anti-nuclear antibodies, anti-smooth muscle antibodies, anti-liver kidney antibodies, anti-mitochondrial antibodies, and IgG levels was all unremarkable. The patient was started on high-dose intravenous Solumedrol and liver function tests (LFTs), and symptoms initially improved during his first few hospital days. However, on the fourth hospital day (day 26 in ), his condition dramatically declined. His LFTs rose rapidly to the thousands, resulting in fulminant liver failure. He then developed acute renal failure, anion gap metabolic acidosis, and hyperkalemia. The patient was placed on a bicarbonate drip, and efforts were made to reverse his acidosis to stabilize him; however, his condition continued to decline and LFTs continued to worsen (AST: 7,708 U/L, ALT: 3,131 U/L, alkaline phosphatase: 817 U/L, and total bilirubin: 11.9 mg/dL). Mycophenolate mofetil 1,000 mg IV was administered with no improvement. The patient was not a liver transplant candidate because of his metastatic cancer diagnosis. The fulminant hepatic failure was irreversible and led to death secondary to cardiorespiratory arrest.


A 57-year-old asymptomatic female patient was referred for a 33 × 27 mm solid lesion arising from the lower pole of the left kidney, which was diagnosed by computed tomography (CT) performed in the context of annual surveillance (). She had been diagnosed with primary lung ACC seven years earlier and underwent right lower lobectomy, without any further adjuvant treatment. On precontrast CT images, the lesion appeared well-circumscribed, homogeneous, and relatively hypodense (30 +/-5 HU). It enhanced slightly in the arterial phase (45 +/-5 HU), but the enhancement was more pronounced in the venous phase (65 +/-5 HU). On 18F-fluorodeoxyglucose positron emission tomography–CT scan (), a lump-shaped radioactive concentration shadow was observed at the lower pole of the left kidney, with a maximum standardized uptake value of 7. No other metastatic lesions were detected. Based on imaging characteristics and the patient's history, the differential diagnosis included nonclear cell renal cell carcinoma, renal metastasis, and benign renal tumors.
According to the Oncology Department's protocol for small renal masses (≤4 cm in greatest dimension) of questionable origin, percutaneous CT-guided biopsy of the renal lesion was performed, and histopathological analysis revealed a pattern compatible with ACC, similar to the primary lung tumor. Given the patient's age and the features of the tumor, nephron-sparing surgery was recommended. The patient underwent laparoscopic transperitoneal partial nephrectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day two.
Gross examination of the specimen revealed a well-circumscribed, solid, and whitish tumor, measuring 37 × 39 × 35 mm. Microscopically, tumor cells were arranged in typical cribriform, tubular, and focally solid growth patterns. Neoplastic cells were small with scant cytoplasm. The stroma manifested myxoid and hyalinized features surrounded by tumor cells forming cylindrical structures (). Immunohistochemically, neoplastic cells showed focal cytoplasmic or very weak nuclear expression of PAX8 which was considered a negative result. The strong nuclear staining of the renal tubular epithelium was used as an internal positive control. PAX8 negativity confirmed the extrarenal and extra-Müllerian origin of the tumor. The epithelial cells showed positivity for CD117 and CK7, and the myoepithelial cells showed positivity for P63, highlighting the dual cell population of the neoplasm, a typical feature of adenoid cystic carcinoma. Surgical margins were negative. These findings confirmed a completely excised metastatic ACC. Follow-up imaging at 24 months showed no evidence of recurrent disease.


A 67-year-old man presented to the emergency department with a 3-day history of progressive right knee pain and inability to bear weight on the affected leg. In the emergency department, he was afebrile and had no reported history of trauma. Plain radiographs of the knee demonstrated evidence of an effusion with moderate-to-severe osteoarthritis and intact screws from a 1996 anterior cruciate ligament (ACL) reconstruction (Figure ). An arthrocentesis was done and showed a cell count of 43,000/mm3 white blood cells with 95% leukocytes and no crystals. Gram stain showed 3+ polymorphonuclear neutrophils (PMNs) and 1+ monocytes. Erythrocyte sedimentation rate and C-reactive protein were both elevated to 16 mm/hr and 6.09 mg/dL, respectively. The remainder of his laboratory evaluation to include complete blood count (CBC), BMP, and uric acid were all within normal limits.
The patient was admitted and taken to the operating room for arthroscopic irrigation and débridement of the right knee for presumed septic arthritis based on his clinical presentation. Magnetic resonance imaging (MRI) is not part of our standard workup for infection and was not obtained before surgical intervention. Cultures were taken intraoperatively, and diagnostic arthroscopy revealed notable synovitis throughout the knee and a mass invested in the synovium (Figure ). There was also evidence of articular erosion in the medial compartment. The mass was excised and sent for biopsy, later confirmed as TGCT (Figure ). The patient was discharged after three sets of cultures remained negative and had down trending inflammatory markers. At the 2-week, 6-month, and 2-year follow-up, the patient demonstrated no evidence of recurrent symptomatic pathology.


Mr. F, a 65-year-old male, was brought to the psychiatric outpatient clinic by his family who reported labile mood, impulsivity, decreased need for sleep, grandiosity, talkativeness, and increased goal-directed behaviors for 3 weeks. Several instances of physical aggression toward family members and self-harm were also reported. He also reported auditory hallucinations without visual hallucinations. A trigger event occurred one month previously, when his affairs were discovered by his family. He initially became depressed and anxious and then experienced mania, as mentioned above, a week later. The patient was oriented and communicable at the clinic despite his irritability. Late-onset bipolar I disorder was diagnosed, and a combination of valproic acid 500 mg/day and olanzapine 10 mg/day was prescribed for acute mania. The subsequent laboratory examination revealed balanced electrolytes, normal thyroid function, and negative syphilis rapid plasma reagin (RPR). Electroencephalography (EEG) showed mild diffuse cortical dysfunction.
The patient's condition improved gradually within the first week of psychiatric treatment. However, he became more agitated and paranoid thereafter, with aggravated auditory hallucinations and persecutory delusions. These symptoms did not improve despite titrating valproic acid to 1000 mg/day and switching from olanzapine to paliperidone 9 mg/day. He was hospitalized in the acute psychiatric ward, and his blood tests and chest X-ray were unremarkable.
In the first 2 weeks of hospitalization, the patient remained agitated and paranoid, and he was frequently placed in a seclusion and protection room (SPR) due to concerns about safety and maintaining his sleep schedule. With the medication adjustment, the patient's clinical condition improved gradually. He was discharged after 6 weeks of hospitalization; the discharge regimen was valproic acid 500 mg/day, aripiprazole 20 mg/day, and quetiapine 150 mg/day. Psychological tests before discharge were performed; the cognitive abilities screening instrument-2.0 (CASI-2.0) score was 82.5/100, and the clinical dementia rating scale (CDR) score was 0.5.
In the following 8 months, his mood remained stable and no psychosis was observed; therefore, the medication was gradually tapered to valproic acid 500 mg/day and quetiapine 50 mg/day. We performed brain magnetic resonance imaging (MRI) to exclude other physiological causes of late-onset bipolar disorder; the findings showed only old, small insults and atrophy. However, after remaining stable for another year, the patient developed acute cognitive function decline and an unsteady gait for 2 months. Laboratory blood tests were unremarkable, while cerebral positron emission tomography (PET) showed decreased [18F]2-fluoro-2-deoxy-D-glucose (FDG) uptake in the cortex regions, compatible with typical Alzheimer's disease. Psychological tests revealed a CASI-2.0 score of 73.4/100 and a CDR score of 0.5, so rivastigmine 9 mg was given. Despite the prescription of antidementia drugs, the patient experienced exacerbations of disorientation, paranoia, delusions involving theft, delusions involving jealousy, visual hallucination, irritability, negative thoughts, insecure feelings, and inappropriate behaviors. These symptoms were considered to be attributed to behavioral and psychological symptoms of dementia (BPSD).
One month later, a neuropsychological assessment was performed because of the presentation of severe clinical dementia, with a CDR score of 2 (). His rapidly declining cognitive function was alarming, but there were no remarkable neurologic deficits or physiological abnormalities at that time. Three months later, his family reported progressive left side extremity weakness and frequent choking for a week, so he was referred to the emergency room (ER) by the outpatient clinic. Laboratory blood tests were still unremarkable, but a chest X-ray showed a mass in the right upper lobe of the lung (). Brain computed tomography (CT) and MRI revealed a mass lesion in the left occipito-parietotemporal lobe, sized 8.4 cm × 4.4 cm × 6.0 cm, with a midline shift to the right (). Malignant origin was favored, and neurosurgery specialists were consulted for evaluation.
Given the concern about the effect of this large tumor and the rapid progression of neurologic deficits, the patient underwent emergency tumor removal surgery. The pathological report showed metastatic adenocarcinoma of pulmonary origin. Whole-body CT with a contrast agent revealed a necrotic lung mass in the right upper lobe and a solid lung nodule in the left upper lobe. FDG PET-CT confirmed right upper lung cancer with lung-to-lung and distant brain metastasis. The patient was then transferred to a pulmonary oncologist for chemotherapy.
The patient did not take any psychiatric medication after surgery; however, valproic acid 1000 mg/day was prescribed by the neurosurgery specialist for postbrain surgery seizure prophylaxis.


A 65-year-old Caucasian male with past medical history of alcoholism, kidney stones, and bleeding gastric ulcer presented to the emergency department of a large community hospital with right lower quadrant abdominal pain that had acutely worsened. He had low-grade pain for two weeks and associated nausea. The patient had noted progressive fatigue but denied abdominal fullness, blood in his stool, dark tarry stools, and early satiety. He did note 15-20 pound weight loss in the past year. His past surgical history included an appendectomy, cholecystectomy, and esophagogastroduodenoscopy (EGD) with intervention for bleeding gastric ulcer. The patient reported he had a colonoscopy in the past but this was unable to be confirmed and no records were found in our electronic medical record of this procedure.
On physical exam, the patient had significant right lower quadrant tenderness with involuntary guarding and focal peritonitis. Significant laboratory findings revealed leukocytosis 28,400/mL (absolute neutrophil count 26.13), anemia with hemoglobin of 7.4 g/dL, thrombocytosis 549,000/uL, bicarbonate 19 mEq/L, magnesium 1.7 mEq/L, and lactic acidosis 2.9 mmol/L. CT of abdomen/pelvis with intravenous (IV) contrast demonstrated marked eccentric thickening and irregularity of the proximal portion of the ascending colon with adjacent stranding and irregular cavity-like appearance containing air with multiple focal areas of free intraperitoneal air in the right mid-abdomen (Figure ).
The patient was started on IV vancomycin and piperacillin/tazobactam and taken to the operating room for exploratory laparotomy. A large mass measuring 8.0x7.5x3.0 cm was noted within the right colon and cecum with a punctate area that was leaking air and mucous. The mass was invading the small bowel and mesentery about 5 cm proximal to the terminal ileum. A right hemicolectomy was performed taking the small bowel in an en bloc resection and taking the mesentery down to its root in order to harvest sufficient lymph nodes for staging. Primary stapled anastomosis between the colon and small bowel was made. The patient tolerated the procedure well.
In the immediate postoperative period the patient required 4 units of packed red blood cells (PRBC). CT chest with IV contrast was performed during admission significant for two cardio phrenic lymph nodes which were likely reactive and thoracic aortic aneurysm 4.5 cm in size. The remainder of his hospital course was uneventful and the patient recovered appropriately. The patient was deemed stable for discharge on postoperative day eight.
The mass was diagnosed as high-grade leiomyosarcoma based on histologic and immunohistochemical findings. The leiomyosarcoma invaded through the cecal wall to involve the adjacent mesentery, but did not invade adjacent organs. Lymphovascular invasion was absent (15 nodes negative) and margins were negative. Microscopically the most active areas of the tumor contain 12 mitoses per 10 high power fields with necrosis involving 40% of the tumor sampled, indicating a Grade 3 tumor based on the French Federation of Cancer Centers Sarcoma Group (FNCLCC) Grading system (Figure ). Furthermore, immunohistochemistry showed malignant spindle cells that exhibited desmin positive (Figure ), actin negative, cluster of differentiation (CD) 117 negative, CD 34 negative, AE1/AE3 negative, s100 negative, and cytokeratin 20 (CK 20) negative. Pathologic staging T2b N0 Mx.
The specimen was re-reviewed at a tertiary care center due to uncommon pathology at a local community hospital and updated to be DDLS with myogenic and osteosarcomatous differentiation in a background of well-differentiated liposarcoma. The sarcoma also involved one of 15 lymph nodes which may have been a direct extension of the tumor onto the lymph node. Based on the new findings upon re-review, American Joint Committee on Cancer (AJCC) stage was changed to Stage III (T2b, N0, M0, GS) making this a high-grade DDLS. A multi-specialty tumor board recommended adjuvant chemotherapy with doxorubicin/ifosfamide once the patient had recovered from surgery.
The patient presented to the emergency department a week prior to the start of chemotherapy, approximately 10 weeks from index operation, with increased abdominal pain. CT Chest/Abdomen/Pelvis was performed and was significant for development of two new metastatic nodules within the left lung apex and superior right middle lobe measuring 4 mm, extensive hepatic metastatic disease with mass in the anterior segment right hepatic lobe measuring 4.4 x 3.0 cm, and development of multiple peritoneal implant masses within the right lower quadrant and left lower quadrant with pelvic ascites. Soon thereafter, the patient was to be unable to keep the first chemotherapy appointment and was documented to be deceased a week later, approximately three months after the index operation.


A 77-year-old Caucasian man presented with a livid discoloration of the left ear, which had first appeared about five days prior to the patient’s flight home from Colombia, where he had spent a two-week vacation, including a stay of several days on a banana plantation in the department of Cundinamarca. The patient remembered a mosquito bite to his left ear during his stay in Colombia. Since his return, he had been experiencing increasing weakness and shortness of breath. The patient had been diagnosed with CLL four years earlier and was currently on ibrutinib therapy. Upon presentation, the patient was in a stable cardiorespiratory state (blood pressure 139/75 mmHg [18.5/10.0 kPa]), heart rate was 92 beats per minute, body temperature was 36.6 °C (309.8 K), and peripheral oxygen saturation (SpO2) was 100% with 2 L of oxygen. Physical examination showed a lividly discolored area on the left ear (Fig. a) and several erythematous, elevated, nodule-like skin lesions disseminated on the torso and extremities (Fig. b, including an eschar-like necrotic skin lesion on the right forearm. CLL treatment with ibrutinib was discontinued. Laboratory tests demonstrated abnormal serum electrolytes (sodium 132 mmol/L, potassium 3.2 mmol/L), acute renal insufficiency (serum creatinine 2.6 mg/dL [229.8 μmol/L], blood urea nitrogen 37 mg/dL [6.2 mmol/L]), mild anemia (hemoglobin, 13.2 g/dL [8.20 mmol/L]), metabolic acidosis (pH 7.353, HCO3 17.6 mmol/L, lactate 3.9 mmol/L), and elevated C-reactive protein (CRP, 29.5 mg/dL [2809.5 mmol/L]). The leukocyte count was within the normal range with a relative increase in monocytes (leukocytes 5.04 G/L with 35% neutrophils, 31% lymphocytes, and 25% monocytes). A chest computed tomography (CT) scan revealed bilateral pulmonary lesions (Fig. c). Given the patient’s recent travel history and the eschar-like presentation of some of the lesions, a tropical disease was suspected. Skin biopsies were obtained from the right ear and right forearm after starting antimicrobial treatment with piperacillin/tazobactam (4.5 g tid) in combination with liposomal amphotericin B (400 mg/day) and doxycycline (100 mg bid) to provide empiric coverage against leishmania, endemic mycosis such as histoplasmosis, and atypical bacterial infections such as rickettsiosis. Within 24 h of the biopsy, the patient’s condition rapidly deteriorated. He developed further skin lesions as well as a rapidly progressive phlegmon starting from the biopsy site on the right forearm. The patient was transferred to the intensive care unit (ICU) due to septic shock and required high-dose catecholamine therapy (maximum dosis during shock: 600 μg/h norepinephrine and 1400 μg/h epinephrine) along with mechanical ventilation. Antibiotic therapy was escalated to imipenem, doxycycline, and amphotericin B. Surgical excision was performed on the progressively inflamed area on the right arm (Fig. d). Histological evaluation showed an acute phlegmonous infection with necrosis (Fig. ). Blood cultures remained sterile. The skin specimens were tested for chagas, babesia, leishmania, endemic mycosis, tuberculosis, cryptococcosis, and rickettsia, but yielded negative results. Finally, microbiological cultures of the necrotic area on the patient’s ear, right forearm, and bronchoalveolar lavage (BAL) revealed the growth of P. aeruginosa, with comparable antibiotic susceptibility testing results showing susceptibility to piperacillin, ceftazidime, cefepime, carbapenems, aztreonam, and aminoglycosides. Thus, a diagnosis of Ecthyma gangrenosum was established. After 8 days of antibiotic treatment and almost daily surgical debridement of the right arm, the patient’s clinical condition significantly improved while the microbiological cultures remained sterile. Liposomal amphotericin B and doxycycline were stopped, and treatment with piperacillin (4 g tid) was continued. Surgical debridement was not performed for skin lesions apart from those on the right arm because these nodules either disappeared or significantly decreased in size, and the systemic inflammatory markers (CRP) also normalized with antimicrobial treatment. Finally, antimicrobial treatment was discontinued 50 days after the patient’s initial presentation, and he was transferred to a rehabilitation facility (Fig. ).
Three and a half weeks after discontinuation of the antibiotic therapy, the patient presented again to the emergency department (ED) with an elevated CRP and recurrence of the skin lesions on the extremities and torso. Physical examination showed red bullous skin lesions with a liquid interior, some of which again displayed a central black eschar (Fig. e). Wound swabs demonstrated growth of P. aeruginosa, and susceptibility testing revealed unchanged susceptibility patterns. Antibiotic treatment with high-dose piperacillin (4 g qid) was initiated and one week later, aztreonam (2 g bid) was added due to the persistent growth of P. aeruginosa in follow-up wound swab cultures, and because the patient had contraindications to aminoglycoside therapy (pre-existing hearing impairment). Recurrent surgical incisions of all the remaining skin lesions were performed. Although the serum IgG and IgM levels were within the normal range, impaired functionality of immunoglobulins (Ig) was assumed due to the underlying CLL [, ], and a total of 30 g Ig were administered intravenously once on day 90. Eventually, no bacterial growth was detected in repeat wound swabs and no new skin lesions were observed (Fig. ) after 23 days of treatment with piperacillin and 15 days of simultaneous treatment with aztreonam. Antibiotic treatment was well tolerated by the patient. The patient was released from the hospital and given ciprofloxacin 750 mg bid for another seven days. Clinical follow-up examination four months after the discontinuation of antibiotic treatment revealed normal inflammation markers and no further skin lesions.


A 70-year-old woman, with a history of osteoarthritis in both hands, visited the emergency room (ER) with a 3-day history of fever. Two weeks prior to this she had developed rashes on her abdomen and mouth but had no other focal symptoms. A systolic murmur was noticed and the patient described that this had been already noted during her childhood. Workup was unremarkable and a viral infection was suspected.
The patient returned to the ER five days later due to continued fever. A temperature of 38.4 °C was noted, CRP was 123 mg/L and small excoriations were noted around the mouth. A clinical diagnosis of impetigo was made. The cultures taken from the mouth sores demonstrated growth of Staphylococcus aureus and blood cultures were negative. The patient was treated with flucloxacillin, 1 g three times daily for ten days.
Eleven days later, the patient returned to the ER again and was admitted due to the persistent fever. Blood cultures were drawn while the patient was still on flucloxacillin. Leukocyte count was 16,000 cells/μL with 15,000 neutrophils/μL, CRP was 85 mg/L and ESR was 58 mm. An echocardiogram was performed first transthoracically (TTE) and five days later transesophageally (TEE). TTE revealed a mobile structure (12 × 14 mm) highly suggestive of a vegetation on the tricuspid valve (). Five days later a TEE was performed which showed an unspecific thickening of the tricuspid valve and mild tricuspid regurgitation but no typical vegetation (). Since blood cultures were negative and TEE inconclusive, additional work-up was performed. A pulmonary X-ray demonstrated an enlarged mediastinum, and thus a computed tomography (CT) of thorax was performed revealing bilateral pulmonary embolism, enlarged mediastinal lymph nodes and a soft tissue tumor of 4.5 × 4 × 3 cm in the mediastinum (). Treatment with 100 mg enoxaparin once daily subcutaneously was initiated. No antimicrobials were given. During the hospital stay, CRP rose from 85 to 177 mg/L but the patient was clinically stable and wished to leave the hospital for further out-patient follow-up. Repeated blood cultures were negative. Further diagnostic workup was performed at a specialized policlinic at the oncology department.
An FDG PET-CT was performed and showed a moderate uptake of the mediastinal tumor as well as in the lungs corresponding to the location of the pulmonary emboli previously noted on CT scan. A focal hypermetabolism was also seen in the caecum which was suspected to be an adenoma. To obtain a diagnosis of the mediastinal tumour a middle-sized-needle biopsy guided by a CT scan was performed and revealed a histological and immunohistochemical picture compatible with a thymoma. An endobronchial ultrasound with transbronchial needle aspiration from the enlarged lymph nodes was performed and cytology was benign.
The condition of the patient worsened with continuous fever, malaise, weight loss and fatigue. A colonoscopy was performed two months after initial presentation and a 2 cm lobulated polyp from the ascending colon and one broad based polyp from the sigmoid colon were removed. Histology report displayed low-grade dysplasia and no signs of malignancy. At colonoscopy the patient was found to be in a poor general condition with dyspnea at rest and pitting edema of the legs. The lungs were auscultated with bilateral rattles.
The patient was again admitted but was afebrile. Haemoglobin was 8.1 g/dL, CRP was 167 mg/L and white cell blood count was 19,000 cells/μl. Blood cultures were obtained and all bottles showed growth of C. canimorsus. Species determination was performed using MALDI-TOF MS with a score of 2.1. ETESTs were performed using Müller-Hinton fastidious agar (MHF) and demonstrated a minimal inhibitory concentration of 0.032 μg/mL for benzylpenicillin. Thus, intravenous benzylpenicillin treatment (5000 units (three grams) four times daily) was initiated. The patient was asked about animal contact and acknowledged that she had dogs that had licked her skin. However, she assured that she had not been bitten.
Repeat TEE demonstrated a large and mobile vegetation (20 × 30 mm) on a partially destroyed tricuspid valve with severe tricuspid regurgitation (). A multi-diciplinary endocarditis conference deemed surgery necessary and the patient successfully underwent biological tricuspid valve replacement and concomitantly a transsternal thymectomy. Postoperatively the patient showed signs of right heart failure and the TTE revealed moderately reduced right ventricular function, necessitating two days of diuretics and inotropic drugs. Cultures from the excised valve showed no growth, but DNA from C. canimorsus was detected using 16S rRNA gene PCR followed by sequencing. The histological examination of the thymoma demonstrated that the resection was radical. Post-operative antimicrobial treatment consisted of two weeks of benzylpenicillin. Postoperative recovery was slow but uneventful. A TTE three weeks after surgery demonstrated mildly reduced right ventricle function and a normal biological tricuspid valve. The patient felt fully recovered, and there were no signs of inflammation at a check-up four months after surgery.


We present the case of a large concealed paravaginal haematoma as a cause of severe postpartum haemorrhage.
A 30-year-old primiparous woman presented at 40 weeks and 1 day of gestation in early labour. Her pregnancy was complicated by the diagnosis of a small for gestational age baby (abdominal circumference 5th percentile, estimated fetal weight 3260 g [26th centile]) on ultrasound at 39 weeks and 5 days. Otherwise she had an uncomplicated antenatal course.
The patient received an epidural block and augmentation of labour with oxytocin and progressed well in labour with a 1st stage of 5 h and 45 min and 2nd stage of 35 min.
A fetal bradycardia was noted on cardiotocography at full cervical dilatation and a live male infant weighing 2740 g was delivered by Neville Barnes forceps in one pull, positioned directly occipito-anterior from the level of the ischial spines. The baby had Apgar scores of 8 at one minute and 9 at five minutes. A right mediolateral episiotomy was made and repaired without complication. Estimated blood loss was 400mLs immediately postpartum and mother and baby were well.
3.5 h postpartum the patient was hypotensive, with a BP of 80/40 mmHg, and heart rate of 94 bpm despite 1 L of intravenous fluid resuscitation and minimal vaginal bleeding postpartum. She complained of worsening rectal pain despite being given oxycodone 5 mg and morphine 10 mg subcutaneously. On examination the uterine fundus was deviated to the right and palpable well above the umbilicus. On vaginal examination there was a large palpable mass extending up the right vaginal wall. Repeat haemoglobin was 7.1 g/dL, down from 13.2 g/dL intrapartum, with normal platelets and coagulation studies.
An urgent computerised tomography (CT) examination of the abdomen and pelvis with intravenous contrast demonstrated two extraperitoneal haematomas without active extravasation. The largest measured 7 cm × 8 cm × 12 cm, lying paravaginally and extending superiorly into the supralevator and extraperitoneal space, displacing the bladder, rectum and uterus []. The second haematoma was located in the extraperitoneal space, underlying the right broad ligament and measuring 12 cm × 2.8 cm × 6 cm on axial CT [].
An initial plan was made to proceed to theatre for examination under anaesthetic and consideration of incision and drainage of the haematoma but the patient's blood pressure improved to 100/50 mmHg and heart rate to 60 bpm. Given the location of the haematoma and the patient's haemodynamic stability, a decision was made for conservative management with ongoing fluid resuscitation, transfusion of one unit of packed red blood cells, analgesia and commencement of intravenous antibiotics to prevent secondary infection of the haematomas.
The patient's pelvic and rectal pain improved significantly day one postpartum and resolved by discharge on day three postpartum. She completed a two-week course of oral cephalexin and metronidazole and remained well postpartum. Repeat CT of the abdomen and pelvis demonstrated partial resolution of the two haematomas, the largest measuring 6.3 cm × 4.6 cm × 4.5 cm on repeat imaging (). The patient was reviewed on day 20 postpartum and was well, with no perineal bruising or palpable vaginal wall haematoma and a haemoglobin level of 10.2 g/dL, up from 9.4 g/dL at the time of discharge.


The patient is a 29-year-old G3P0111 with monochorionic diamniotic twins diagnosed with vasa previa by transvaginal ultrasound at 16-week gestation (). Her prior pregnancy was complicated by preterm labor and delivery at 36-week gestation. The current pregnancy was otherwise uneventful, and the plan was for inpatient observation starting at 30 weeks with planned cesarean delivery to avoid labor.
At 29-week gestation, the patient presented with preterm contractions. Betamethasone was administered for fetal organ maturation, and magnesium sulfate was given for neuroprotection. She had persistent preterm contractions with cervical effacement, and therefore, cesarean delivery was indicated. During the low transverse hysterotomy, unprotected umbilical vessels were visualized. Amniotomy was performed while avoiding these vessels, and clear amniotic fluid was noted. Twin male neonates were delivered with Apgar scores 8/8 and birth weights of 1.26 kg and 1.33 kg for A and B, respectively. Both twins were evaluated and admitted to the NICU. Cord gases and hemoglobin for both twins were normal.
The remainder of the surgery was uncomplicated. Gross inspection of the placenta and membranes confirmed vasa previa affecting both fetuses (see Figures and ). Placental pathology confirmed membranous insertion of the umbilical cord for twin A and twin B. The postpartum course was unremarkable, and NICU courses for infants were typical for gestational age. At the time of this writing, both twins are doing well and meeting appropriate milestones.


A 53-year-old man presented to the emergency department of another hospital with abdominal pain and severe weight loss (12 kilograms). An abdominal CT scan showed a 10-cm left retroperitoneal mass. According to the latest European Society for Medical Oncology (ESMO) Guidelines [], a CT-guided PCNB was performed. The diagnosis was as follows: leiomyosarcoma, of at least Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade 2 []. In light of the diagnosis of sarcoma and the appearance of sub-ileus symptoms with increased abdominal pain, the patient was transferred to our referral sarcoma center. A new CT scan was performed, which showed an increase in the volume of the left retroperitoneal necrotic mass (about 15 cm) and an intraperitoneal accumulation of fluid evoking a hemoperitoneum (Figure ).
The tumor was in direct contact with the left kidney, the pancreatic tail, and the psoas muscle. The superior mesenteric artery was free of infiltration. The chest CT scan was normal. Blood examination revealed severe malnutrition: hemoglobin of 9.6 g/dl, albumin of 24.8 g/l, and prealbumin 0.14 g/l. The coronavirus disease (COVID-19) nasal swab test was negative. Considering the clinical deterioration of the patient and the presence of hemoperitoneum, which proved the spontaneous bleeding of the mass, the decision to conduct surgery as a delayed emergency was made. A median laparotomy extending transversally to the left flank was performed, and 2.5 liters of hemorrhagic ascites were evacuated. A large tumor perforation was identified in the distal part of the tumor with colon perforation. The tumor had extensively invaded the peritoneal layer and it was spontaneously bleeding over the entire surface. The left kidney was completely encompassed by the tumor. The first step of surgical resection was the liberation of the root of the mesentery, contiguous but not infiltrated by the tumor. After coloepiploic separation, transverse colon and rectosigmoid junction were divided. The distal pancreas and spleen were indivisible from the tumor. Given the extension of the mass, we decided to perform a distal splenopancreatectomy. Vascular dissection was performed from the iliac vessels up to the aorta with a sub-adventitial dissection. In the left iliac fossa, the ureter was divided, and the femoral nerve was isolated. The left renal vein and artery were divided by stapler and ligation, respectively. The left psoas fascia was detached from the vertebra and it was left posteriorly to the tumor. Finally, the tumor was removed en-bloc with the left kidney, ipsilateral colon, mesocolon, spleen, and distal pancreas in front, aponeurosis of the psoas in the back, and parietal peritoneum on the side of the mass (Figure ). The omentum was used to fill the surgical bed.
The postoperative course was characterized by intrabdominal bleeding due to a pancreatic fistula, which was treated at first by a splenic artery embolization on the 10th postoperative day (POD) and then by an exploratory laparotomy on the 14th POD. During surgery, no active bleeding had been found and peritoneal cavity lavage with saline solution had been performed. After the resolution of the pancreatic fistula, the surgical drains were removed and the patient was discharged on the 42nd POD. The histological exam revealed a 16-cm dedifferentiated leiomyosarcoma (FNCLCC grade 3). The tumor showed high mitotic activity (23 mitoses/10 high-power fields) and areas of necrosis (up to 50%). Resection margins were negative. Tumor rupture and colic perforation were confirmed by the pathologist. The multidisciplinary tumor board composed of surgical oncologists, oncologists, radiotherapists, radiologists, and pathologists discussed the clinical case after surgery and decided to have the patient undergo follow-up. A thoracoabdominal CT scan after four months was recommended. No further adjuvant systemic treatments were deemed to be indicated in this case.