A 26-year-old man underwent a chest X-ray for an annual check-up, which showed a protrusion of the aortopulmonary window (Fig. ). Seven months later, he was referred to our hospital without symptoms. He had a past history of epilepsy with medication. He was a never smoker, but he was exposed to organic solvent due to his work as a researcher of carbon fiber. Chest CT revealed a thin-walled multilocular cystic tumor, 9.0 cm in diameter, in the anterior mediastinum. The septum of the tumor was enhanced by contrast medicine (Fig. a). The tumor compressed the left brachiocephalic vein, but seemed not to have invaded the surrounding structures. The serum level of carcinoembryonic antigen was slightly elevated (5.4 ng/ml; normal value, less than 5.0 ng/ml); however, other tumor markers including alfa-fetoprotein, beta-human chorionic gonadotropin, anti-acetylcholine receptor antibody, and soluble interleukin-2 receptor were not elevated. Magnetic resonance imaging (MRI) showed a multilocular cystic lesion with focal mural nodules in the anterior mediastinum (Fig. b). The preoperative diagnosis was a cystic thymoma, or a malignant lymphoma. We did not perform needle biopsy for diagnosis preoperatively, due to thin cystic wall. We performed a total resection of the tumor through a median sternotomy. The tumor was fully covered with fibrous capsule with partly dense adhesion to the left mediastinal pleura. Needle aspiration cytology of cystic fluid was done during surgery, and the result was class V (suspicion of seminoma) (Fig. ). The left mediastinal pleura was resected with the tumor. The pathological diagnosis was seminoma with multilocular thymic cysts. Higher magnification showed large polygonal cells with clear cytoplasm, round or oval nuclei, and prominent nucleoli; immunohistochemical stain for c-kit, oct3/4, d2-40, and placental-like alkaline phosphatase stain was positive, and beta-human chorionic gonadotropin stain was negative []. So, these cells were diagnosed as seminoma cells. The cysts were lined by only normal squamous epithelium, and cyst walls were characterized by inflammatory changes (Fig. –). Testicular ultrasound imaging and abdominal, pelvic, and cerebral CTs did not show any apparent tumors or enlarged lymph nodes preoperatively. However, FDG-PET scan revealed an abnormal uptake (maximal standardized uptake value was 6.8) in the right mesenteric lymph node (Fig. a). The patient was classified as intermediate risk group due to suspicion of mesenteric lymph node metastasis, so received four courses of BEP (20 mg/m2 cisplatin on days 1–5, 100 mg/m2 etoposide on days 1–5, and 30kU bleomycin on days 1, 8, and 15, repeated 21 days) as adjuvant chemotherapy. Follow-up PET scan revealed no uptake in the right mesenteric lymph node (Fig. ). To date, no recurrence or metastasis has been identified for 16 months.


A 21-year-old woman with a past medical history of one uncomplicated urinary tract infection with a pan-sensitive urine culture presented to the emergency department (ED) with 2 days of new right-sided abdominal pain, noting some radiation to back. The patient had two episodes of nonbloody/nonbilious emesis the day before the encounter, but was able to tolerate liquids on day of the visit. The patient denied dysuria or other urinary changes. Vital signs were notable for a temperature of 100.9 °F and a heart rate of 130 bpm. Examination elicited right upper quadrant tenderness and right lateral abdominal tenderness, but no rigidity or rebound tenderness. The patient was nontender elsewhere, including the suprapubic region. While performing a right upper quadrant point-of-care ultrasound to assess for biliary pathology, a negative sonographic Murphy sign was noted, while maximal tenderness was found directly over the ipsilateral kidney, in all orientations []. Tenderness increased with increasing pressure applied by the ultrasound probe. There were no other notable kidney abnormalities and the immediately adjacent areas were nontender to sonopalpation. Subsequent urinalysis testing was remarkable for nitrites and leukocyte esterase. The patient was successfully treated as an outpatient with cephalexin. At one month follow-up, the patient reported resolution of symptoms after the antibiotic course.


A 19-year-old female with a history of recurrent but uncomplicated urinary tract infections presented to the ED with dysuria for 3–4 days and bilateral flank, back, and lateral abdominal pain, worse on the left. The patient noted nausea and one episode of vomiting at home. In the ED, the patient had normal vital signs but was uncomfortable and unable to tolerate oral pain medications. On physical examination, the patient was tender to palpation in the left mid-lateral abdomen, left lower back, and left costovertebral region. Point-of-care ultrasound delineated these non-specific findings and demonstrated maximal tenderness with direct sonopalpation over the left kidney (which demonstrated no hydronephrosis.) The patient was subsequently admitted for intravenous ceftriaxone, fluids, antiemetics, and pain control. Urinalysis revealed large leukocytes and a urine culture grew ampicillin-resistant but otherwise pan-sensitive Escherichia coli. Blood testing revealed no electrolyte abnormalities or leukocytosis, though an 80% neutrophil predominance was noted. A non-contrast computed tomography of the abdomen revealed no renal stones or perinephric stranding. A radiology suite ultrasound showed no hydronephrosis. The patient improved with antibiotic treatment and was discharged without complication on the 2nd day of hospitalization.


A 37-year-old woman with no past medical history presented to the ED with a chief complaint of headache, body pain, and minimal dark vaginal discharge. In triage, she was febrile to 102.8 °F and tachycardic to 138 beats per minute and thus triggered a sepsis alert. She denied dysuria or pelvic pain. She also denied symptoms consistent with upper respiratory infections or gastrointestinal infections. She exhibited no altered mental status, neck pain, stiffness, or rash. On review of symptoms, she complained of mild right mid back pain. Her examination was unremarkable, including a normal pelvic examination. While she denied oliguria, the patient was initially unable to provide urine. A chest X-ray was normal. Initial lactate was normal at 1.8 mmol/L. Given no clear source of infection, imipenem-cilastatin was ordered. However, before the antibiotic was administered, a point-of-care ultrasound was performed demonstrating unequivocal and maximal tenderness to the right kidney on sonopalpation. At this point, the patient was able to produce a small amount of urine, and point-of-care urinalysis demonstrated 3+ blood and small leukocyte esterase. Given this, the diagnosis of pyelonephritis was made and ceftriaxone was administered instead of imipenem–cilastatin. Blood tests resulted as unremarkable, and urine culture and gonorrhea and chlamydia tests results were pending. The patient remained tachycardic in the 110 s for two more hours and her oral temperature improved to 99.8 °F. The patient was admitted to the ED observation unit for further doses of intravenous ceftriaxone where she improved dramatically over the subsequent 12 h and was discharged. She completed a course of oral antibiotics with excellent response. On follow-up, the urine culture grew E. coli and gonorrhea and chlamydia tests were negative.


A 25-year-old obese woman with an intrauterine contraceptive device in place for two years presented to the ED with 7 days of dysuria and “colicky” nonradiating suprapubic pain which worsened one day earlier. She complained of a new fever and lower back pain in the past day, but no other infectious symptoms other than one year of occasional mild white vaginal discharge and trace vaginal spotting associated with the end of her menstruation. She stated a monogamous sexual relationship with no new partners. In triage, her temperature was 100.8 °F with otherwise unremarkable vital signs. On examination, she had moderate suprapubic tenderness. She also had tenderness in the right lower back. Because of obesity, costovertebral angle tenderness could not be definitively established. Subsequent point-of-care ultrasound demonstrated a maximal area of tenderness well inferior to the patient’s right kidney, which was relatively superior and medial, in this patient. A bimanual pelvic examination was then performed, demonstrating mild cervical erythema and localized tenderness in the right adnexal region. An endocervical swab was obtained for gonococcal and chlamydia testing. Urinalysis revealed moderate leukocyte esterase. The patient was empirically treated for pelvic inflammatory disease with intramuscular ceftriaxone and oral doxycycline. She was also treated with oral cephalexin in the case of non-pyuric cystitis. The urine culture grew no organisms. The endocervical swab was positive for chlamydia. The patient was notified and advised to notify her partner. No complications were reported on a subsequent unrelated ED visit four months later.


A 74-year-old male with a history of liver cirrhosis due to alcohol abuse was diagnosed with a mass in the right liver lobe at ultrasonography. A subsequent liver CT revealed a multifocal, hypervascular mass in segments 5 and 8 of the liver with contrast washout, consistent with HCC. The largest tumour measured 3.7 cm (tumour involvement 1%). Cirrhosis, splenomegaly and gastro-esophageal varices were also present, but no ascites or portal vein thrombosis. The day of treatment, he was graded as Child-Pugh grade A6/ALBI score grade 1 (Table ).
The LSF was 9%. He underwent a right lobar treatment (3,1 GBq, target dose 80 Gy). Posttreatment 90Y-PET/CT showed adequate targeting of the lesion in segments 5 (306 Gy) and 8 (376 Gy). The average absorbed dose of the non-tumorous liver parenchyma was 33 Gy.
Twelve days after treatment, he visited the outpatient clinic with complaints of increasing abdominal girth and weight. He was treated with a low sodium diet and diuretics. Six weeks thereafter, he was readmitted because of decompensated cirrhosis with worsening encephalopathy. At 3-month follow-up, laboratory tests showed grade 2 bilirubin (2.4 mg/dL), grade 3 albumin (20 g/L), grade 1 ALP, AST and ALT toxicity and an elevated ammonia serum value (60 μmol/L). Concurrent liver CT showed ascites in all quadrants, shrinkage of the liver and partial necrosis of the HCC’s (partial response of the smaller tumours and stable disease of the largest tumour).
Evaluation of the hepatobiliary scintigraphies showed a whole liver function decline from 3.0 to 2.4%/min/m2 (Table ). The function of the treated right hemiliver declined from 2.3 to 1.6%/min/m2, without evident hypertrophy of the left hemiliver (0.8 vs 0.7%/min/m2).
He died 4 months after RE due to hepatic failure, probably caused by REILD.


A homeless 57-year-old male with a history of cirrhosis due to alcohol abuse was diagnosed with a multifocal HCC. MRI liver revealed four hypervascular lesions in segments 1 (1.0 cm), 5 (4.4 cm) and 8 (3.2 and 0.8 cm), consistent with HCC (tumour involvement 1%). Coexisting liver cirrhosis, portal hypertension and a moderate amount of ascites was also present, but no portal vein thrombus. At diagnosis, he had decompensated cirrhosis, which was recompensated 5 months later at treatment. He had a Child-Pugh grade B8 at treatment (ALBI grade 3) (Table ). The LSF was 4%.
He underwent a right lobar treatment (2.5 GBq, target dose 100 Gy). The posttreatment 90Y-PET/CT showed reasonable targeting, but also a relatively large amount of activity in the tumour-free segments 6 and 7 with an average absorbed dose of 91 Gy (Fig. ). The absorbed dose for the tumours in segments 1, 5 and 8 was 226, 63 and 227 Gy, respectively. The absorbed dose of the smallest tumour (0.8 cm) could not reliably be measured.
Fourteen days after treatment, he was readmitted with increasing ascites and peripheral oedema, consistent with decompensated cirrhosis. Two days later, he developed a spontaneous bacterial peritonitis, successfully managed with albumin suppletion and antibiotics.
At 3-month follow-up, his liver function had further declined to Child Pugh grade C11, with a grade 3 bilirubin toxicity (Table ). Follow-up MRI at that time showed a partial response of all four lesions, consistent with the decrease in AFP levels. However, also massive ascites and shrinkage of the liver were noted.
At 3-month follow-up, his liver function had declined to 0.6%/min/m2 (1.8%/min/m2 at baseline). The pre-RE liver function was mainly located in the right hemiliver (1.6%/min/m2). After RE, this declined to 0.4%/min/m2, without compensatory function increase of the left hemiliver (stable at 0.2%/min/m2).
He died 4 months after RE treatment due to definite REILD (Fig. ).


A 74-year-old male with a history of hepatitis B and cirrhosis (Child Pugh grade C11/ALBI grade 3) was diagnosed with multifocal HCC, which was initially left untreated because of decompensated cirrhosis. After 6 months, he was admitted because of severe haemorrhage of one lesion. He was treated with bland coiling of the arterial supply to this lesion. Another 12 months later, his cirrhosis had recompensated (Child Pugh grade B8/ALBI grade 2) and he opted for RE. At that time, his MRI revealed a large HCC located in segment 7/8 (6.6 cm), in segment 4 (6.3 cm) and two smaller lesions in segment 6 (tumour involvement 19%). No portal vein thrombus was present. The LSF was 11%.
He underwent a right lobar treatment (2 GBq; target dose 120 Gy). The posttreatment 90Y-PET/CT showed adequate targeting of lesions in segment 6 (243 and 422 Gy) and segment 7/8 (309 Gy). The average absorbed dose of the non-tumorous parenchyma was 32 Gy. Subsequent treatment of segment 4 was cancelled, because of uncorrectable extrahepatic deposition and a LSF of 25% on 99mTc-MAA SPECT/CT 1 month later.
Follow-up MRI at 3 and 6 months showed a partial response of the lesions in segments 6 and 7/8, but progressive growth of the lesion in segment 4. At 3-month follow-up, the function of the treated liver volume had declined to 0.8%/min/m2 (1.5%/min/m2 at baseline), whereas the non-treated volume showed a minimal functional improvement from 0.7 to 1.0%/min/m2 (Fig. ), resulting in a decline of the total liver function from 2.2 to 1.8%/min/m2.
He died 1 year after RE due to tumour progression (not due to REILD).


A 20-year-old Japanese woman was working in a restaurant and experienced discomfort in her left thigh on the seventh day before her hospital admission. On the next day, she felt pain in the same area while walking, and subsequently consulted a physician, who prescribed an antiphlogistic sedative patch on the fifth day before her admission. On the third day before her admission, she developed a fever (38 °C) and subsequently consulted another physician, who prescribed an antipyretic drug. However, she continued to experience fever and pain in her left thigh flexor during rest. Therefore, she consulted another physician and was admitted to our hospital, where she was prescribed a single dose of acetaminophen (400 mg). She did not have a history of domestic or overseas travel, participation in outdoor activities, or trauma.
Upon admission, she had a blood pressure of 110/63 mmHg, a pulse of 107 beats/min, a respiratory rate of 16 breaths/min, and a temperature of 38.9 °C. Her left thigh flexor appeared slightly red, with mild swelling, warmth, and pain. However, her head, lungs, heart, abdomen, and back did not exhibit redness or swelling. Her white blood cell count was 12,100 cells/mm3, her hemoglobin level was 10.8 g/dL, and her C-reactive protein level was 24.11 mg/dL. Her liver and renal functions were normal, and the HIV antibody/p24 antigen test (fourth generation) provided negative results. However, enhanced computed tomography (CT) revealed fluid between the dorsal distal muscles of her left thigh and an enhanced margin of fluid (Fig. ), which we diagnosed as an abscess. There were no other abscess-like formations outside of her lower extremities.
An incision was made in her left thigh on the day of admission, the abscess was continuously drained, and we treated her using ampicillin/sulbactam (four doses per day, up to 12 g daily). Two sets of blood cultures provided negative results; however, a culture of a fasciotomy specimen from the abscess revealed positive results for GAS. Definitive identification of the GAS isolate was performed using the rapid streptococcus test (Rapid ID32 STREP; bioMerieux SA, Marcy l’Etoile, France). Therefore, we changed the patient’s treatment to penicillin G (24 million units per day via continuous infusion) on day 5. However, drug eruption in response to the penicillin G was suspected on day 12, and we changed the antibiotic to clindamycin on day 13 (2700 mg in three doses per day). We stopped the continuous drainage on day 15, and switched the treatment to oral clindamycin on day 16 (600 mg three times per day). The patient was discharged after 17 days in the hospital, and her antibiotic treatment lasted 4 weeks. We did not observe any side effects that were related to the clindamycin treatment. The patient has remained in good health during the 1-year follow-up after her discharge from the hospital.


A 22-year-old male patient from India, with no significant past medical history, presented to us with complaints of fever, pain in small joints of hands with morning stiffness, skin rash over both the elbows and knees, redness and pain in both the external ears, and generalized weakness for one month. His appetite was reduced and he had lost three kilograms of body weight during this period. There was no history of paraesthesia over any body part. He had previously received two courses of broad spectrum antibiotics from his family physician without any relief. He was afebrile at presentation and had normal pulse rate and blood pressure. His general physical examination revealed mild pallor, symmetrical rash over extensor aspects of both the elbows without any loss of sensation () and redness of upper two-thirds of both the external ears with sparing of lobules (). There was no palpable nerve thickening. His musculoskeletal examination revealed tenderness over bilateral metacarpophalangeal and interphalangeal joints and his hand squeeze was tender. There was no obvious joint swelling.
His investigations revealed hemoglobin 10.5 g/dl, total leukocyte count 12700/mm3, platelet count 179000/mm3, and raised inflammatory markers (ESR 112 mm/hour and CRP 11.27 mg/L). His kidney and liver function tests were normal except for reversed albumin/globulin ratio. Urine routine examination showed 10–15 RBCs/hpf and twenty-four hours' urinary protein estimation was 540 mg. Plain radiogram of the chest was normal.
In view of history of auricular chondritis, rash, inflammatory joint pain, constitutional symptoms, and proteinuria his autoimmune antibody profile was done. Complement levels, RF, ANA, and anti-neutrophil cytoplasmic antibodies (ANCA) were negative. His HIV screen was also negative. In view of the typical chondritis of the ear with sparing of noncartilaginous portion, relapsing polychondritis was considered as the possible diagnosis. Granulomatosis with polyangiitis was also kept as a differential but was less likely in view of the absence of sinus and pulmonary involvement and negative ANCA report. Bacterial chondritis was not considered as he had previously received courses of antibiotics without any benefit and had a long history of one-month duration. Trauma and radiation exposure are other rare causes of chondritis which were ruled out by appropriate questioning.
Skin biopsy from the lesions over elbows was done which showed unremarkable epidermis and dermis with perivascular and periadnexal lymphohistiocytic collection and ill formed granuloma. Ziehl–Neelsen stain was positive for acid fast bacilli, and positive Fite-Faraco stain further confirmed the diagnosis of leprosy.
Patient was treated with the combination of clofazimine, dapsone, and rifampicin. He became symptom-free after six months of treatment with complete clearance of skin rash and ear lesions. His joint pain and constitutional symptoms of fever and anorexia have subsided and he has regained his lost weight and feeling of wellbeing. He is still in the maintenance phase of treatment.


A 42-year-old asymptomatic female presented to our institution for routine screening breast study. The patient had family history of breast cancer (her mother at 45 years). Physical examination was normal.
Mammography showed an architectural distortion in the upper quadrants of the left breast, only clearly seen in the mediolateral oblique view (). DBT—routinely performed at the patient's hospital—localized the lesion to the upper outer quadrant and further characterized it as a small irregular mass with long spicules (). A targeted Ultrasound (US) showed a 10 mm solid nodule, with posterior acoustic shadowing (). A tru-cut biopsy guided by US was performed, revealing a tubular carcinoma.
Breast Magnetic Resonance Imaging (MRI) was done to evaluate the local extension and showed, apart from this nodule, an additional one 8 mm in the upper inner quadrant, with the same imaging findings at MRI and US, and at a distance of 35 mm from the former (). It was biopsied at second-look US, and the histologic diagnosis was also tubular carcinoma.


The patient was a 74-year-old female. Edema appeared in the upper left limb 6 weeks prior to hospitalization. A computed tomography (CT) scan revealed a thrombus in the left subclavian vein with adjacent lymphadenopathy. Therefore, anticoagulant therapy was initiated. The CT scan also showed the presence of ascites and wall thickening of the greater curvature of the gastric corpus, which prompted us to perform upper gastrointestinal endoscopy. The tumor found in the greater curvature of the middle body in the stomach was biopsied and diagnosed as adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma; Fig. ). On 2-deoxy-2-(18F) fluoro-d-glucose positron emission tomography/computed tomography imaging (PET/CT), accumulation was detected in the entire stomach; in the portal and posterior area of the right hepatic lobe; in the cervical, left supraclavicular, left axillary, left parasternal, and superior mediastinal lymph nodes (which suggested extensive lymph node metastases); and interestingly and unexpectedly, in the thyroid, where 18F-FDG was diffusely taken up in both lobes, for some unknown reason (Fig. a, b). The patient was diagnosed with multiple metastases of gastric signet-ring-cell carcinoma/poorly differentiated adenocarcinoma, and was subsequently admitted to our hospital for chemotherapy. Serum concentrations of carcinoembryonic antigen (CEA), CA19–9, and CA125 were elevated (9.7 ng/mL, 1825.0, and 122.5 U/mL, respectively), consistent with advanced gastric carcinoma. Thyroid gland function was within the standard range. Serum thyroglobulin was supranormal (893 ng/mL). Anti-thyroglobulin and anti-TPO antibodies were negative (Table ).
On day 8 of hospitalization, the patient complained of bilateral neck swelling with pain on the left side. A CT scan was ordered, and it showed edema of the chin, neck, and anterior chest and increased density of adipose tissue. As for the thyroid, both the lobes were diffusely enlarged and exhibited low density on CT (Fig. c). Because PET revealed that a significant accumulation in the whole thyroid and antithyroid autoantibodies was negative, we suspected diffuse infiltration of gastric carcinoma cells into the thyroid. Therefore, ultrasound examination and aspiration cytology were performed.
On ultrasonography, diffuse enlargement of the thyroid gland was seen (right lobe, 51 × 25 × 26 mm; left lobe, 49 × 51 × 20 mm; thickness of the isthmus, 10 mm), and it appeared internally heterogeneous. Nodular lesions were not detected, and hypoechoic reticular lines were observed in some places. On color Doppler imaging, the blood-flow signal was low (Fig. : imaging by Aplio-XG; TOSHIBA Medical Systems Corporation). The fine-needle aspiration cytology sample obtained from the right lobe revealed discohesive cells with severe nuclear atypia. Notably, there were cells with large cytoplasmic mucin vacuoles and cells with a high nuclear-to-cytoplasmic ratio. These findings indicated that the thyroid lesion was categorized as “malignant” (metastatic carcinoma) according to the Bethesda system for reporting thyroid cytopathology (TBSRTC) [], and were consistent with the metastasis of the gastric signet-ring-cell carcinoma/poorly differentiated adenocarcinoma to the thyroid gland (Fig. ). In addition, skin biopsy from the swollen anterior chest revealed insular tumor cells in the dermis, small blood vessels, and lymphatics. The vascular and lymphatic microembolizations caused by tumor cells established the diagnosis of cutaneous metastasis. Subsequently, the patient’s respiratory tract edema worsened, as confirmed by laryngoscopy, and glucocorticoids were administered. Chemotherapy with paclitaxel was done only once, because severe cytopenia occurred and her performance status became Eastern Cooperative Oncology Group (ECOG) class 4. Despite our best supportive care, the patient died a month after hospitalization. An autopsy was not performed.


A 28-year-old-male patient presented on June 9, 2016 to the health post of Pikine (sub-urban of Dakar) for headache, vomiting, diarrhea, low back pain and arthralgia. Suspecting malaria, an HRP2-based RDT specific to Plasmodium falciparum was performed. The test was positive for falciparum malaria. Following the Senegalese national policy guidelines for the treatment for uncomplicated malaria, the patient was given artemether 20 mg + lumefantrine 120 mg at admission and every 8 h for a total of six doses. Four days later, the patient was referred to Aristide Le Dantec Hospital. He presented with fever (39 °C), soreness, abdominal pain and vomiting.
The onset of symptoms had occurred brutally 4 days before, marked by intense and not radiating back pain without triggers or calming factors. There was also continuous soreness and joint pain without any particular pattern, associating intense asthenia, which is temporarily relieved by usual analgesics. There was also diffuse headache, without axial stiffness. There was no photophobia nor phonophobia, associating with vomiting and nausea, two to three fluids diarrhoeas that lasted 3 days without fever nor concept of eating suspected food and no similar cases in the entourage.
Investigations shown that the patient was from Velingara (south of Senegal) and had come to Dakar 2 months earlier. He had no previous medical history. The blood pressure was 120/80 mmHg. There was no sign of clinical anaemia. The rest of the examination was normal. Laboratory test showed thrombocytopenia (platelets 40 × 109/mm3) as the only abnormal haematological test. A thick film from peripheral blood was performed and sent to the parasitology laboratory of Le Dantec Hospital. Thick film was stained with 10% Giemsa. Trophozoite of P. falciparum was identified at parasite density of 47 parasites per microlitre. In addition, spirochetes of Borrelia were observed indicating a malaria co-infection with borreliosis (Fig. ).
Treatment consisted of doxycycline 200 mg daily during 14 days. No further symptoms were noted. Effectiveness of treatment was confirmed by negative microscopy for both malaria parasites and spirochetes.


The patient was a 73-year-old woman with a prior medical history of hypertension who presented with three weeks of dyspnea, nausea, loose stools, and fatigue. Examination was unremarkable. However, complete blood count (CBC) revealed leukocytes of 240,000/μL, hemoglobin of 6.2 g/dL, and platelets of 119,000/μL (). Peripheral smear showed many promonocytes and a few immature blasts containing rare Auer rods consistent with a diagnosis of AML. Emergent leukopheresis and treatment with hydroxyurea were initiated. Bone marrow biopsy and aspirate showed 73% myeloblasts and immature promonocytes expressing CD13, CD15, CD33, CD45, CD64, CD123, and HLA-DR by immunohistochemistry (IHC) and flow cytometry (FC). Cytogenetic analysis showed a normal karyotype. FLT-3 ITD and exon 12 mutation of the nucleophosmin-1 (NPM1) gene were detected (data not shown). Findings were consistent with NPM1-mutated AML of FAB M5 subtype.
Induction chemotherapy with standard-dose cytarabine (100 mg/m2 once daily × 7 days) and daunorubicin (45 mg/m2 once daily × 3 days) was initiated. The patient achieved a complete remission (CR) based on count recovery and repeat bone marrow aspirate showing no blasts or promonocytes. At the time of morphologic CR, no FLT3 mutation was identified by quantitative PCR in the marrow; however, exon 12 mutation of NPM1 was identified in a very small fraction of the cells (signal was below the 10% sensitivity control). Allogeneic stem cell transplantation was offered given the high risk for disease progression, but patient declined. She subsequently received two cycles of high-dose cytarabine (1.5 g/m2 once daily × 6 days), which she tolerated well with complete count recovery.
Six months after completion of consolidation therapy and eight months from her diagnosis, the patient was noted on routine follow-up to have mild leukopenia of 3,300/μL and thrombocytopenia of 115,000/μL. Repeat bone marrow biopsy and aspirate () showed 64% myeloblasts which expressed a slightly different immunophenotype than originally (CD13, CD33, CD15, CD58, CD117, and HLA-DR). Cytogenetics revealed a new abnormality in the form of del (15q) in 19/20 analyzed cells. Both NPM1 and FLT3 ITD mutations were identified with a FLT3 ITD allele/wild-type ratio of 0.36.
The patient was referred to a clinical trial of an experimental FLT3 inhibitor. She underwent screening bone marrow biopsy and aspirate () on the contralateral side from BM-1 approximately one week apart. Surprisingly, this demonstrated cellular marrow with 3% blasts without Auer rods and no evidence of AML by marrow IHC and FC. Cytogenetics revealed del (15q) in 1/20 analyzed cells. Molecular analyses detected the presence of a very small amount of NPM1 mutation in the blood and marrow and a minimal amount of FLT3 with an allelic ratio of 0.005 in the peripheral blood only. The patient reported no interim known or suspected infections or administration of blood products between BM-1 and BM-2. Given these incongruent marrow findings, another bone marrow biopsy and aspirate procedure () was performed on the ipsilateral side as BM-1 another week later. This specimen also showed no evidence of AML by morphology or FC with 2% blasts. Cytogenetics revealed del (15q) in 6/20 analyzed cells. Molecular analyses on marrow aspirate showed detectable NPM1 and FLT3 mutations with a FLT3 ITD allele/wild-type ratio of 0.01. To confirm that these marrow samples were indeed from the same patient, genomic DNA was extracted from the BM-1, BM-2, and BM-3 marrow samples followed by amplification of nine short tandem repeat loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, and D7S820) using the AmpFLSTR® Profiler Plus® PCR Amplification Kit from Life Technologies. All of the samples had identical results at all nine loci, thus confirming that the specimens were from the same individual. Unfortunately the patient was not deemed a candidate for clinical trial of experimental FLT3 inhibitor due to the lack of overt morphological disease, which was an eligibility criterion. She elected to resume observant therapy.
Thirty-five days from first documented SR (BM-2), the patient presented with overt disease recurrence with leukocytes of 29,900/μL and 16% peripheral blasts. Marrow biopsy revealed 84% myeloblasts with del (15q) in all 20 analyzed cells and new del (16q) in 1 of 20 cells. Molecular analyses confirmed the same NPM1 and FLT3 ITD mutations with a high allelic ratio of 1.99. The patient decided to forego further treatment and died a few weeks later.


A 35-year-old African American female was admitted to an outside hospital with an 8-month history of abdominal discomfort, bloating, transient arthralgia, and unintentional weight loss of 60 pounds. A CT scan of the abdomen and pelvis showed a large complex left retroperitoneal mass, abdominal ascites, and pleural effusions, contiguous with the left adnexa. She was found to have hemoglobin of 4.9 g/dL and received blood transfusions prior to transfer to Cooper University Hospital.
Given the abnormal CT scan and her 60-pound weight loss, she underwent an exploratory laparotomy which revealed a large hematoma extending up the left pelvic wall to the kidney, mesosalpinx of the left adnexa, and 300 mL of ascites. As malignancy was a major concern, a total abdominal hysterectomy, right oophorectomy, bilateral salpingectomy, left pelvic lymph node dissection, omentectomy, and evacuation of the retroperitoneal hematoma were performed. Frozen tissue pathology was obtained and revealed hemorrhage and no malignancy.
After her surgery, the rheumatology service was consulted. Her exam was remarkable for a fever of 101.2 F, discoid lesions on her ears, a distended abdomen, and 1+ pedal edema. The abnormal labs included a hemoglobin of 8.2 g/dL (microcytic), lymphopenia 0.9 k/ul (with normal WBC = 6 k/ul), creatinine 1.4 mg/dL, and urinalysis with 3+ protein, 2+ blood, 16 WBCs, 36 RBCs, and 1+ granular casts. A repeat CT of the abdomen and pelvis () showed multiple pelvic and retroperitoneal fluid collections.
Postoperatively, renal function worsened with associated oliguria. There was increased concern for an underlying glomerulonephropathy after records from the outside hospital revealed a positive ANA (1 : 1280), CH50 < 13, and 7 grams of proteinuria. Additional labs at our facility revealed positive ENA to SCL-70, anti-DNA, RNP antibody, Smith antibody, SSA antibody, and low complements. Antiglomerular basement membrane antibody, ANCA screen, rheumatoid factor, cryoglobulin, HIV-1/2 antibody, and hepatitis viral panel were all negative. The final pathology report revealed a left ovary/fallopian tube organizing hematoma, with vasculitis of the small and medium sized blood vessels involving the uterus, cervix, right fallopian tube, paratubal tissue, and omentum ().
Due to the patient fulfilling both the 1997 ACR and 2012 SLICC SLE classification criteria, she received IV pulse methylprednisolone, followed by oral prednisone 1 mg/kg and mycophenolate mofetil. A kidney biopsy was deferred due to increased risk of hemorrhage. Her renal function continued to improve and she was discharged on prednisone 60 mg daily with immunosuppressive therapy.


A one week old male Ayrshire calf with a swelling on parieto-occipital region of the head was referred to the Faculty of Veterinary Medicine and Surgery of Egerton University. From history, the swelling was initially smaller at birth but progressively increased in size. The calf’s appetite was normal and was bottle-fed by the owner.
The calf was always lying on lateral recumbency, with a roughly spherical fluctuant saclike protrusion on parieto-occipital region of the head, measuring 12x13cm and covered with hairy skin (Fig. ). The calf exhibited resistance and groaned on deep palpation and neck flexion. Rectal temperature of 38.4 °C, respiration of 22 breaths per minute and pulse of 130 beats per minute were recorded. On deep palpation, the rim of the cranial bone defect could be felt around the base of the swelling. On palpation of the rostro-dorsal wall of the swelling, a hard, roughly wedge-shaped structure could be felt. Lateral head and neck radiographs revealed homogeneity of the swelling’s content suggestive of a fluid-filled cyst with no neural/brain tissue involvement (Fig. ).
Straw-colored fluid, with glucose level of 8.2 mg/dl, was aspirated from the cyst. The calf was then euthanized followed by complete opening of the cyst where a total volume of 600 mL of liquid was obtained. The cyst was connected to the cranial cavity via an almost perfectly circular defect in parieto-occipital region of skull vault with a diameter of 5 cm and through which the caudal pole of the cerebral hemispheres and rostral part of cerebellum could be seen (Figs. and ). The cerebral hemispheres appeared wide apart while the cerebellum was displaced caudally so that transverse fissure was remarkably enlarged exposing part of corpus quadrigermina with the cerebellar hemispheres appearing abnormally wide apart.
The liquid in the cyst was contained within a meningeal sac, which was relatively thick walled and adherent to the inner surface of the overlying hairy skin and to both the margin of the bone defect and inner surface of cranial bones. The sac was continuous with the brain meninges (Fig. ) and its inner surface had features akin organ impressions, characterized by depressions separated by pillars of elevated tissue. Embedded to the wall of the meningeal sac was a narrow longitudinally oriented tongue-shaped bony structure. This structure measured 7.3 cm in length and was wider at the middle, measuring 1.8 cm, and then tapered gradually towards both extremities.


A 29 year old previously healthy African American male with sickle cell trait sought evaluation for new onset hematuria. Computed tomography (CT) imaging showed a lesion at the pole of his left kidney and aortocaval lymphadenopathy; a biopsy was consistent with renal medullary carcinoma. He underwent an open left partial nephrectomy with retroperitoneal lymph node dissection. Surgical pathology showed a 2.2 cm tumor with positive margins, Fuhrman nuclear grade 4, involvement of the renal pelvis, and lymphatic invasion with an associated mass of lymph nodes measuring 3 cm in diameter (AJCC stage III – pT1aN1Mx). Next generation sequencing identified only two genomic alterations of known significance, including the loss of SMARCB1 as a homozyogous copy number deletion, and a frame shift mutation in ARID2 (H1495fs*8).
The patient started an adjuvant treatment regimen of carboplatin AUC of 4, gemcitabine at 1000 mg/m2, and paclitaxel at 80 mg/m2 with the addition of bevacizumab. He experienced significant cytopenias requiring 20% dose reduction to complete 6 cycles of therapy, after which he had no evidence of disease based on imaging. He proceeded with interval cross-sectional imaging every 3 months and had enlargement of a para-aortic lymph node consistent with disease recurrence within 7 months of completing chemotherapy. The patient was reluctant to resume chemotherapy at the time of recurrence due to his prior difficulties with cytopenias and was offered localized therapy with intensity-modulated radiation therapy followed by radiosurgical boost. At completion of his radiotherapy, PET imaging showed resolution of the para-aortic lymph node targeted by radiation, but multiple new enlarged sub-carinal and mediastinal lymph nodes (Fig. ).
He then underwent flexible bronchoscopy and biopsy of a right paratracheal lymph node that confirmed disease recurrence. He was initiated on treatment with nivolumab, a PD-1 inhibitor, at 3 mg/kg every two weeks. On his initial CT scan, he was found to have an excellent partial response. At the time of this report, the patient has continued to tolerate nivolumab well with only mild fatigue, and has worked full-time throughout treatment. Now nine months after initiation of PD-1 inhibition, his CT scan showed complete response (Fig. ) almost 32 months from the time of his initial diagnosis.
To elucidate the mechanisms and immune correlates of his response to therapy, we obtained archival tissue from his metastatic, pre-treatment biopsy of the subcarinal lymph node. We performed fluorescent immunohistochemistry using automated quantitative analysis (AQUA®; Genoptix, Inc) to profile the tumor microenvironment. This assay demonstrated substantial expression of PD-L1 (E1L3N antibody) by 23% of tumor cells, and modest expression of both PD-1 and PD-L1 by stromal components (2% and 5% of cells respectively; Fig. ). Robust expression of both CD8 (10% stromal expression) and CD4 (41% stromal expression) were also demonstrated among infiltrating lymphocytes. Notably, a high percentage of T cells were also positive for CTLA4 (31%). Total infiltrating T cells comprised 21% of all cells in the sample. Interestingly, next generation sequencing of 315 genes (FoundationOne®, Foundation Medicine) showed an extremely overall low mutational burden (projected as <1 mutation/MB).


A 38-year-old female presented with a large posterior cavity nasal mass that was being expectantly observed by outside physicians for years. However, on presentation, she endorsed worsening headaches, troublesome nasal obstruction affecting sleep, and intermittent nausea and vomiting without associated photophobia. Physical examination and neck radiograph imaging suggested a diagnosis of KFS with the patient exhibiting webbing of the neck, cleft lip and palate, and midline cranial and cervical anomalies including C2/C3 cervical fusion. Office endoscopy revealed a complex, mobile, midline mucosalized mass filling the entire posterior nasal airway with extension into the superior oropharynx through a cleft in the soft palate ().
Computed tomography angiography (CTA) revealed a 4 × 4 cm multiloculated, nasal mass of the sphenoid skull base protruding through a “central corridor” in the sphenoid intersinus septum of the basisphenoid and anterosuperior to the clivus bone (Figures and ). Magnetic resonance imaging (MRI) demonstrated a pedunculated, extradural heterogeneous mass extending into the nasopharynx, with high intensity fat signal seen within the tumor and its sizeable stalk on T1 sequence (). Rare pituitary duplication () and the enlarged intracranial basilar cistern with bright CSF fluid signal are readily noted on T2 sequence (). The tumor stalk was felt to represent a patent/persistent craniopharyngeal duct, and multiple other midline intracranial abnormalities including corpus callosum dysgenesis, midline lipoma, and dysmorphic hypothalamic and brainstem changes were also noted (not shown). CTA was also performed out of concern for large caliber vascular pedicle to the tumor, with only limited axial blood supply noted (). Given the patients' crescendo in symptoms and the collective imaging findings, an extended endonasal resection of this skull base teratoma was planned between otolaryngology and neurosurgery.
Access was obtained via inferior turbinate outfracture and limited posterior septectomy to permit binarial access. A two-surgeon, four-handed surgical approach, and intraoperative, computer-assisted image guidance confirmed unfettered access to the teratoma, with classic dentition seen in triplanar view (). The main consideration was control of the midline stalk at the skull base without encountering a cerebrospinal fluid (CSF) leak from the basilar cistern or intracranial retraction of vascular feeders from the pedicle. The stalk, measuring approximately 1 cm laterally and 1.5 anteroposteriorly, was encased in a bony shell that extended through the midline floor of the sphenoid sinuses into the upper clivus. Using hand instruments and fine diamond drill bits, the ensconced stalk was liberated from the surrounding bone. This revealed a fibrovascular pedicle that was then cleanly truncated using the Thunderbeat™ device, for simultaneous ultrasonic wave (cutting) and bipolar diathermy (coagulation) action. The technique permitted transmural pedicle resection, precluding the need for awkward suture ligation of a thick pedicle adjacent to the skull base, while allowing for the tumor to be delivered en bloc transorally (). Microscopic analysis of the resected tumor using standard histology revealed a disordered arrangements of mature epithelial and mesenchymal tissues, including cartilage, adipose tissue, stratified squamous epithelium with cutaneous-type adnexal structures, ciliated respiratory-type epithelium, and striated muscle (). No immature neural element was identified, consistent with a mature teratoma. No perioperative complications were noted, with resolution of all preoperative symptoms within 1 month. Postoperatively, in the absence of the obstructive mass, a palatal obturator was required to limit nasal regurgitation and hypernasal speech through coverage of the cleft palate defect. She continues to do well >3 years since surgery, with no untoward sequelae from the procedure.


A 56-year-old female presented with a four-week history of increasing shortness of breath, cough, and mild dysphonia. She had been treated with antibiotics for chest X-ray demonstrated pneumonia during this time but received little benefit. On examination she was found to be “wheezy” on auscultation of the chest and she was admitted under the respiratory service.
A new diagnosis of asthma was suggested for which she was started on salbutamol nebulizers and oral prednisone forty milligrams. She made little progress and suffered sporadic episodes of oxygen desaturation. On day nine of admission, a computed tomography scan of the chest demonstrated known pulmonary metastases and an irregular appearance of the larynx. On the tenth day of admission, an otolaryngology consult was sought.
The patient's medical history was significant for locally advanced, Stage IIIb (T4, N1, M0), adenocarcinoma of the rectum which was diagnosed and treated eight years prior to this episode. Adenocarcinoma treatment involved chemoradiation with Capecitabine as an adjunct for abdominoperineal excision of the rectum with vertical rectus abdominis myocutaneous flap. Four years after her initial treatment she required radio-frequency ablation for lung and liver metastases, she underwent a partial right lung resection five years after initial treatment, and six years after initial treatment she required further radio-frequency ablation of liver and lung metastases. Her metastases proved resistant to radio-frequency ablation and at the time of admission she had received four cycles of palliative Capecitabine and Mitomycin chemotherapy. She had suffered two pulmonary emboli, one six years before this episode and one six months prior, for which she took regular prophylactic low molecular weight heparin.
On otolaryngology review, she had biphasic stridor on deep breathing. Flexible nasendoscopy (FNE) was performed at the bedside which visualized a large nodular subglottic mass. Epinephrine nebulizers and intravenous dexamethasone were initiated. On the day of review, a head and neck operative list was taking place. Between cases, a specialist head and neck otolaryngologist and a specialist “difficult airway” anesthesiologist reviewed the patient with repeat FNE. A decision was quickly made to add the patient to their operative list for surgical resection of the mass while securing the airway.
Intubation was performed with the assistance of the Karl Storz C-MAC video laryngoscope and an endotracheal tube was “railroaded” beyond the subglottic mass with an Eschmann tracheal tube introducer. Microlaryngoscopy demonstrated a large sessile subglottic mass arising from the posterior commissure (). The bulk of this mass was easily removed en masse by a laryngeal grasper. After a surgical pause to assess for bleeding, the endotracheal tube was replaced with jet ventilation to allow for laser resection of the mass remnant and its underlying mucosa; ten watts of carbon dioxide laser was used on super-pulse mode for the resection. Following laser resection the tissue was extremely friable and bleeding followed any contact (). Therefore, in an effort to ensure no further bleeding into the airway, Tisseel fibrin glue (Baxter AG, Vienna, Austria) was applied over the site of laser ablation through a catheter inserted in the operative channel of the bronchoscope with the endoscopic applicator provided by the manufacturer. During Tisseel application, jet ventilation was held for between ninety seconds and two minutes. Two application cycles of Tisseel were employed with five minutes between applications (). Five minutes after the second application of Tisseel cessation of anesthesia was initiated (supplementary video online in Supplementary Material available online at ).
The mass measured twelve millimeters in its longest diameter and was histologically described as moderately differentiated adenocarcinoma morphological consistent with metastatic colorectal carcinoma, with positive expression of Cytokeratin 20 and Caudal Type Homeobox 2 without Cluster of Differentiation 7. Immunohistochemical studies for mismatch repair proteins found no evidence to support a diagnosis of Lynch syndrome. Pathological analysis is therefore strongly suggestive of primary tumor origin in the large intestine, confirming this mass as a metastasis of the patient's rectal adenocarcinoma and not a primary laryngeal tumor.
The patient was closely monitored for forty-eight hours on the high dependency unit with clear instructions to intubate if there was evidence of bleed into the airway. Subsequently she was stepped-down to the ward where significant resolution of her shortness of breath and cough were reported, and oxygen saturations above 96% were maintained throughout. Chest auscultation did not elicit any wheeze. Postoperative speech and language therapy evaluation found excellent speech and swallow function, and the patient was discharged from the speech and language therapy service prior to discharge. She was discharged from hospital one week after the procedure having had an uncomplicated postoperative course. Nine months postoperatively she was clinically stable, without evidence of tumor recurrence within the larynx.


A 57-year-old Japanese woman felt a lump in her left breast more than 10 years previously that remained untreated. She now sought medical attention because the mass increased in size over the last year. Palpation revealed a 10-cm hard, non-movable mass in the medial left breast (Fig. ). Breast ultrasonography (US) showed a large breast mass with slit formation and heterogeneous internal echoes. Fine needle aspiration cytology of the lesion suggested a phyllodes tumor (PT), but needle biopsy suggested a fibroadenoma. Malignancy could not be ruled out based on the clinical course, so vacuum-assisted breast biopsy was performed for qualitative diagnosis. A PT was suspected. Whole-body search included lung computed tomography (CT) that showed multiple metastatic lung tumors (metastatic lesion suspected), but no lymph node metastasis (Fig. ).
A partial mastectomy with 10 mm surgical margin was performed for a definitive diagnosis, and pathological diagnosis of the resected specimen showed a malignant PTB (10.0 cm, f, ly0, v0, ew-, nuclear atypia score 3, mitotic count score 3, nuclear grade 6). Postoperative adjuvant chemotherapy was not given at the patient’s request.
Two months after surgery, masses appeared at the right and left occipital, parietal, and temporal area of the head. Skin biopsy revealed skin metastases from the malignant PT, and these were resected with 10 mm surgical margin. In addition, 7 months after initial surgery, pharyngeal pain, swelling, and a feeling of dyspnea developed, and tumor was found in the left palatine tonsil. CT for further evaluation showed a tonsillar lesion with contrast enhancement, and tonsillar metastasis was suspected (Fig. a, b). The metastatic lung tumors had not progressed. Laryngoscopic biopsy showed a tonsillar metastasis from the malignant PT (Fig. ). Despite the diagnosis of PTB with tonsillar and pulmonary metastases, the patient refused further treatment and died about 1 month later. Palliative care was performed according to the intention of the patient.


A 45-year-old male patient visited the emergency room (ER) because of lower chest discomfort starting 6 hours earlier. He also complained of thirst and limb numbness. His medical history included diabetes mellitus, bronchial asthma, and unstable angina for 4 years, 2 years, and 1 year, respectively. He had been taking aspirin (100 mg/d), clopidogrel (75 mg/d), atorvastatin (10 mg/d), and candesartan (8 mg/d) for 1 year without changes. He took those medicines on the morning of his admission. He regularly used a Symbicort Turbuhaler® (AstraZeneca Korea, Seoul, Republic of Korea) (160/4.5 μg) for asthma management. One month before the present admission, he discontinued the oral hypoglycemic agents prescribed by his primary physician. He denied recent alcohol consumption and had quit smoking 1 year earlier. Except for these symptoms, he initially had no complaints, such as muscular pain, fever, upper respiratory symptoms, or signs, on visiting the ER. He had no history of excessive physical activity or recent trauma.
On initial physical examination in the ER, his vital signs were as follows: blood pressure, 100/60 mm Hg; heart rate, 71 beats/min; respiratory rate, 20 times/min; and body temperature, 36.6 °C. On chest auscultation, no abnormal sounds, such as rales or wheezing, were audible, and his heartbeat was regular without murmur. His general skin turgor was decreased, and his tongue was dry. His conjunctivae were not anemic and sclerae were not icteric. There were no palpable lymph nodes in the head or neck area. Organomegaly was not seen in the abdomen. No pretibial pitting edema, muscular swelling, or skin color changes were detected on either lower extremity. There was no tenderness in the upper or lower extremities. His muscle power was within normal limits.
Compared with a previous ECG, the rhythm and voltage were unchanged. His initial troponin-I was less than 0.1 ng/mL, creatinine kinase (CK) was 144 U/L (0–190 U/L), lactate dehydrogenase (LDH) was 220 U/L (135–225 U/L), and CK-MB, subunit of CK, was 3.5 ng/mL. Other initial laboratory data were hematocrit 45% (39%–52%), hemoglobin 14.5 g/dL (13–17 g/dL), white blood cell count 11,280/mm3 (4000–10,000/mm3, neutrophils: 68.2%, lymphoid cells: 25.6%, and monocytes: 4.5%), and platelet count 256,000/mm3 (130,000–400,000/mm3). Liver function tests were as follows: alkaline phosphatase 84 IU/L (35–130 IU/L), aspartate aminotransferase (AST) 21 IU/L (0–37 IU/L), alanine aminotransferase (ALT) 42 IU/L (0–41 IU/L), and glucose 696 mg/dL. Hemoglobin A1c (HbA1c) was 9.3% (4.2%–5.9%). Blood urea nitrogen (BUN) and creatinine were 19.9 mg/dL (6.0–20.0 mg/dL) and 1.11 mg/dL (0.6–1.2 mg/dL), respectively. Electrolyte results were sodium 123 mmol/L (135–145 mmol/L), potassium 4.7 mmol/L (3.3–5.1 mmol/L), and chloride 80 mmol/L (98–110 mmol/L). Serum osmolality was 296 mOsm/kg. Urinalysis with micro revealed no protein or blood on a dipstick and red blood cell 1 to 4/high-power field.
Continuous intravenous insulin and hydration with normal saline were started. In addition, 40 mg of esomeprazole was infused intravenously under a suspicion of GERD. Glucose levels, measured by a blood sugar meter, decreased to 240 mg/dL and chest discomfort improved 6 hours after this management. In the mean time, there were no other oral, intramuscular, and intravenous drug therapies except for oral lactulose for his constipation. He felt mild discomfort in the right buttock at that time but did not complain to the medical team. However, he complained of severe right buttock pain 12 hours after the esomeprazole infusion. Tender muscle swelling of 8 cm in diameter was seen in the right buttock area and a reddish skin color change was noted (Fig. ). Serum CK and LDH levels increased to 40,533 and 1326 U/L, respectively, and AST and ALT levels also increased to 320 and 83 IU/L, respectively. BUN and creatinine levels were 23.9 and 1.49 mg/dL, respectively. We started vigorous hydration through isotonic saline infusion and urine alkalinization by intravenous bicarbonate infusion. Another 40 mg of esomeprazole was administered because we did not regard esomeprazole as the causative agent of the rhabdomyolysis at that time. Serum CK, LDH, AST, and ALT levels were 84,226, 1943, 603, and 171 IU/L, respectively, 24 hours later. On the third day in hospital, he was admitted to the nephrology ward. Esomeprazole was ended, and hydration and alkalinization were continued. Serum CK and LDH levels decreased gradually (Fig. A and B), and his muscular symptoms and swelling in the buttock area improved gradually. A bone scan using 20 mCi of 99mTc-hydroxymethylene diphosphonate was performed on the seventh day in hospital and revealed multiple and diffuse uptake in the soft tissues of the right buttock and both lower legs (Fig. ). His clinical manifestations and laboratory findings improved, so he was discharged on the 12th day. We added oral hypoglycemic agents, linagliptin 5 mg and metformin 500 mg, to his previous drugs (aspirin, clopidogrel, candesartan, and atorvastatin). He is being followed in our outpatient department with no recurrence of rhabdomyolysis at 6 months.


A 65-year-old woman had been diagnosed with overlap syndrome (autoimmune hepatitis and primary biliary cirrhosis) for 14 years. Initially, she was prescribed ursodeoxycholic acid and prednisone, and refused immunosuppressive drugs. However, due to the presence of gastric ulcer and economic reasons, she stopped taking these medications. When liver test results were abnormal, she would take compound glycyrrhizin tablets to treat the disease. In September 2013, due to hematemesis and melena, rupture and hemorrhage of the esophagofundal varices was found. Computed tomography revealed cirrhosis of the liver, splenomegaly, and ascites. The disease progressed to Child–Pugh C decompensated cirrhosis. The patient received endoscopic therapy, and began taking prescribed ursodeoxycholic acid 750 mg daily. From September 2013 to August 2015, her alanine aminotransferase (ALT) level fluctuated between 27 and 91 U/L, aspartate aminotransferase between 33 and 94 U/L, γ-glutamyl transpeptidase between 73 and 240 U/L, alkaline phosphatase between 130 and 260 U/L, total bilirubin (TBIL) between 39.3 and 74.05 mol/L, direct bilirubin between 17.6 and 34.24 mol/L, albumin between 30 and 35 g/L, antinuclear antibody (ANA) titer between 1:1000 and 1:3200, and antimitochondrial II antibody (AMA-M2) between (+) and (++). In September 2015, the patient consulted her physician in our department for significant jaundice and weakness. Physical examination revealed yellow pigmentation of the skin and sclerae, positive liver palms, spider angioma on the chest, and positive shifting dullness. Results of liver function tests showed the following: ALT, 499.9 U/L; aspartate aminotransferase, 686.8 U/L; albumin, 27.02 g/L; γ-glutamyl transpeptidase, 87.2 U/L; alkaline phosphatase, 225.6 U/L; TBIL, 329.6 mol/L; direct bilirubin, 272.91 mol/L; cholinesterase, 2156.4 U/L; prothrombin time, 17.7 seconds; percentage prothrombin time activity, 60; and platelet count, 45 × 109/L. The anti-HCV antibody test result was positive and the quantitative HCV RNA test result was 6.1 × 105 IU/mL (genotype 1). The ANA titer was 1:3200, and the AMA-M2 was (+). Epigastric enhanced magnetic resonance imaging identified cirrhosis, splenomegaly, ascites, and collateral circulation in the esophagus, fundus of the stomach, and splenic hilum. Magnetic resonance cholangiopancreatography did not detect any abnormality in the intrahepatic and extrahepatic bile ducts. Initially, the treatment included ursodeoxycholic acid at the previous dosage, glycyrrhizinate, human serum albumin, furosemide, spironolactone, lactulose oral solution, and platelet and clotting factor transfusion. However, after 1 week, weakness and jaundice were exacerbated. Liver function test results were significantly abnormal with a TBIL of 417.6 mol/L, prothrombin time of 23.5 seconds, percentage prothrombin time activity of 46, albumin of 23.1 g/L, cholinesterase of 1789.7 U/L, and platelet count of 14 × 109/L. After ruling out other possible causes of acute hepatitis, we thought that the cause of the acute exacerbation of hepatic damage was AHC infection, as liver function was decreased by HCV activity. After discussing the risks and benefits with the patient, we started her on an IFN-free combination therapy of SOF and weight-based RBV for 12 weeks. Gilead-brand SOF (400 mg/d) was used. SOF cannot be bought in China; the patient acquired the medication through her relative who works abroad. The patient was reviewed at treatment weeks 1, 2, 3, 4, 8, and 12 and at posttreatment weeks 4, 12, 24, and 36. At the beginning of SOF and RBV treatment, the HCV RNA viral load was 4.8 × 106 IU/mL. At week 1, the HCV RNA viral load was reduced to 4330 IU/mL; at week 2, 1790 IU/mL; and at week 3, 750 IU/mL. At weeks 4, 8, 12, 16, 24, 36, and 48 (posttreatment week 36), the HCV viral load was undetectable (Fig. ). By week 4, the patient's symptoms alleviated. By week 8, liver function returned to baseline levels with TBIL of 85.35 mol/L, prothrombin time of 17.0 seconds, albumin of 29.5 g/L, and platelet count of 53.2 × 109/L (Fig. ).


Two siblings, a 13-year-old girl (case 1, Figures –) and a 10-year-old boy (case 2, Figures –) of normal intelligence had come to Chettinad Dental College and Research Institute, Chennai, with a complaint of decayed teeth. The physical appearances were similar, characterized by short stature, short neck, protuberant chest, scoliosis, and a waddling gait. Their facial feature presented frontal bossing and flat nasal bridge. The history revealed that the patients had pain in the hip region on walking that subsides at rest. The parents did not belong to different ethnicity. They had a nonconsanguineous marriage and a family history free from any skeletal disorder. On oral examination, exposed teeth with sharp cusps and rough enamel texture were found (Figures , , , and ). The orthopantomograph showed thin hypoplastic enamel of normal radiodensity (Figures and ).
A multispecialty approach was adopted and medical examination of all major systems revealed no dysfunctional changes. However, the orthopedic and radiographic evaluation indicated gross skeletal deformity. The hand-wrist radiograph showed proximally narrow metacarpals. The anteroposterior view of the spine expressed curvature of the thoracolumbar vertebral segment. The lateral spinal view revealed anterior beaking of the vertebral body (). The pelvic view radiograph revealed an irregularly outlined square-shaped head of the femur and coxa valga defect ().
A diagnosis of mucopolysaccharidosis type IVA was reached based on the clinical, dental, and radiographic findings of the patients. The diagnosis would need to be confirmed by analysis of GALNS enzyme activity and molecular genetic testing of GALNS gene. Unfortunately, parents' consent could not be obtained for this analysis.


This left-hand-dominant 50-year-old male (weight: 112 kg; height: 185 cm; BMI: 33 kg/m2) fell off of his porch on 31 August 2014 and sustained a massive rotator cuff tear (both the supraspinatus and infraspinatus were torn). The subscapularis and teres minor were deemed to be of good quality. Three months later, he had an attempt at repair, but the surgeon found the tendon tear irreparable. It was likely that the patient had a previous but smaller chronic rotator cuff tear from a sports-related injury many years previously. The patient understood that nothing other than a reverse total shoulder arthroplasty could be done to adequately restore shoulder function.
The patient came to our clinic one month after this unsuccessful attempt at repair. Physical examination at that time showed pseudoparalysis as exhibited by active forward flexion and abduction at 60–65° and superior-posterior shoulder subluxations (). We recommended a LDTT. If active range of motion was not achieved to his satisfaction but the graft healed, then he would likely achieve a tenodesis effect. This in turn would help reduce subluxations of his glenohumeral joint and thereby reduce pain while likely increasing active motion to a moderate amount [].
The patient then had an arthroscopic evaluation followed by an open acromioplasty with partial repair of the torn infraspinatus and an open LDTT. The surgery was performed by JGS in accordance with the technique described by Dr. Iannotti and colleagues []. A superior approach to the rotator cuff was made by detaching the deltoid origin from the anterior aspect of the acromion and with splitting of the middle deltoid fibers for 3.5 cm. The coracoacromial ligament was released with the deltoid and reattached at the conclusion of the operation. The bursa was excised, and the rotator cuff was inspected. A second incision was made along the lateral border of the latissimus dorsi muscle, extending to the posterior axillary crease. The LDT insertion was identified with the arm abducted and internally rotated, and it was detached sharply from the humerus. The neurovascular pedicle was identified and protected, and the muscle was released from its deep fascia attachments. A number 2 nonabsorbable suture was passed with use of a Krakow suture technique along each side of the tendon from the musculotendinous junction to the end of the tendon (). Blunt dissection was performed to construct a tunnel deep to the deltoid and superficial to the posterior rotator cuff musculature.
In the conventional surgical technique, the latissimus dorsi muscle and tendon are routinely brought over the top of the humeral head and repaired anterior to the subscapularis, lateral to the greater tuberosity, and medial to the torn edges of the rotator cuff (). However, during surgery, our patient's LDT was found to be only 5 cm long, less than the mean LDT length reported by Goldberg et al. [] (mean: 7.3 cm; range: 6.6–7.8 cm; SD: 0.38 cm) and nearly 5.5 cm shorter than what was needed for an adequate reconstruction. The patient was consented for use of an acellular dermal matrix graft (GraftJacket) but not for other allograft or autograft tissues. The anticipated use of GraftJacket was for augmentation at the repair site. However, GraftJacket has been mechanically tested and was found to be superior in strength to comparable xenografts and allografts (CuffPatch™, Restore, Permacol™, and TissueMend®) []. Additionally, an added layer of thickness from folding the GraftJacket allograft was deemed sufficiently strong to extend the length of the LDT.
Two 4 × 7 cm patches of GraftJacket were used to extend the LDT. The thickness of each patch was 2.0 mm (GraftJacket Maximum Force Extreme; Wright Medical Technologies, Inc.; ). Each patch was folded in half along its short dimension, which resulted in 4 × 3.5 cm patches that were 4.0 mm thick each. The folded margins of the patches were sewn together with number 2 nonabsorbable sutures (). The “biologically resorbable” surface of the GraftJacket was exposed so that it would be in direct contact to the bone at the insertion site for the tendon reconstruction. This surface represents the anatomically deeper part of the graft and it is placed facing the bone in order to allow incorporation of the graft [].
The first patch was overlapped on the free end of the LDT by 12.5 mm and was then sutured with two rows of nonabsorbable number 2 sutures (). The second GraftJacket patch was overlapped by 12.5 mm to the first patch and was sewn with two rows of nonabsorbable number 2 sutures. The total extension of the LDT was then 5.5 cm. A Krakow suture technique with number 2 suture was then passed along the sides of the latissimus tendon to the free end of the graft extension as shown in . As described below, the extended LDT was then attached directly to the “footprint” that was created for the supraspinatus, upper infraspinatus, and upper subscapularis ().
Before attaching the extended LDT to the footprint, residual infraspinatus tendon at the lower portion of the natural insertion site was mobilized by sharp dissection and moved 15 mm upward and sutured to the upper natural insertion site for this muscle. This was done with number 2 FiberWire sutures through drill holes posteriorly and also with the sutures from a Mitek Healix™ anchor that was placed at the location where the supraspinatus and upper infraspinatus naturally merge. This anchor was double-loaded with number Orthocord® sutures.
The LDT with the GraftJacket extension was then pulled upward beneath the posterior deltoid and anteriorly across the defect in the rotator cuff. Along the lateral portion of the footprint, four pairs of horizontal mattress sutures (number 2 FiberWire) were passed through drill holes. The GraftJacket extension was then fastened in place with these number 2 FiberWire sutures and with the two sutures from the aforementioned Mitek Healix anchor. Additional fixation included a series of separate number 2 FiberWire sutures passing through the upper subscapularis and also a series of separate sutures passing medially through the residual supraspinatus tendon near the glenoid. The shoulder was then passively tested for stability and motion; elimination of the posterior-superior subluxations showed that a tenodesis effect was clearly achieved.
After wound closure, the patient was placed in a rigid shoulder orthosis in neutral rotation and 45° abduction for two months, following Gerber et al.'s [] postoperative treatment. Gentle passive shoulder motion was allowed only after 6 weeks. Active overhead motion was not allowed until four months after surgery. Weight bearing exercise at the shoulder was allowed at nine months after surgery but no lifting over 20 lbs (9 kg) overhead until one year after surgery.
At follow-up 18 months later, the patient had regained significant strength and range of motion in his left shoulder ( and ). He reported being very satisfied with the overall results achieved from his surgery. However, he avoided sleeping on his left side because his shoulder “aches really bad” and he reported shoulder fatigue with repetitive overhead reach. He was not taking regular pain medication besides occasional over-the-counter NSAIDs.
At 18 months after his LDTT, magnetic resonance (MR) scanning was done solely for the purpose of examining integrity of the graft. The graft was found to be intact and without evidence of thinning (). Mild glenohumeral arthritis was noted in the MR images, which likely contributed to some of his continuing low-level pain. At final follow-up at two years after surgery, the pain had improved to only trace and his function was maintained.


A previously healthy 37-year-old male was referred to our hospital with a diagnosis of dengue hemorrhagic fever with shock. His clinical course began 6 days prior to transfer when he presented to an outside hospital with fever. He was found to have left sided hemothorax on arrival causing respiratory distress in which intercostal drainage was promptly placed. However, his condition remained unstable following the procedure requiring intravenous norepinephrine for hypotension. His clinical course was shortly complicated by acute renal failure necessitating renal replacement therapy via right internal jugular catheter on hospital day 2. Despite supportive treatment, lactic acidosis was newly demonstrated together with the need for higher dose of vasopressive drug, various antibacterial regimens were prescribed throughout hospitalization and meropenem and vancomycin were selected as initial combination.
On hospital day 3, due to progressive respiratory distress and failure on lung recruitment maneuver, extracorporeal membrane oxygenation (ECMO) was initiated via right femoral catheter. He was also noted to have pancytopenia. Bone marrow study findings were compatible with hemophagocytosis syndrome secondary to dengue infection. Intravenous dexamethasone (10 mg/m2) and intravenous immunoglobulin were started and plasmapheresis replaced immunoglobulin therapy on the following day. Hematologist was able to reverse pancytopenic event 7 days later but profound lymphopenia persisted throughout his hospital course with the highest absolute CD4 count of 90 cells/mm3.
On hospital day 11, ECMO was discontinued and right femoral catheter was removed after stabilization of overall condition. However on hospital day 13, he underwent left below knee amputation for better control of limb ischemia presumably secondary to ECMO complication that had been documented since hospital day 8. His clinical course was also complicated by 1.) Cytomegalovirus reactivation during dexamethasone therapy and required brief duration of ganciclovir treatment given no specific organ involvement identified and 2.) Chromobacterium viloaceum pneumonia and secondary bacteremia on hospital day 18. Bacterial pneumonia was very difficult to control that he required a prolonged course of antibiotics consisting of piperacillin/tazobactam and ciprofloxacin to the point that left pneumonectomy was indicated on hospital day 46. After the surgery, he was prescribed several short courses of antibiotic treatment mainly in order to prevent gut microbial translocation following numerous events of gastrointestinal bleeding. Hemorrhagic complication was later discovered to be secondary to large stress associated rectal ulcer. He died on hospital day 71 due to massive esophageal bleeding that autopsy findings failed to identify infectious etiology at the bleeding site.
Regarding fungal infection risk particularly IA following severe dengue infection, micafungin was begun on hospital day 3 after serum galactomannan (GM) was obtained which later reported to be 2.3 by enzyme-linked immunosorbent assay (ELISA). Liposomal amphotericin B replaced micafungin for new diagnosis of probable IA that chest radiograph now displayed faint opacities in right middle lung field. In addition, anidulafungin was added in response to rapid progression of pulmonary lesions on chest radiograph. After 6 days of combination therapy, serum GM level declined to 0.55 as the lowest value but no change on chest radiograph findings and respiratory status.
On hospital day 18, micafungin replaced anidulafungin in light of possible cardiac toxicity. Bronchoscopy was done to determine the potential pathogenic fungi but biopsy was avoided given very compromised respiratory status. Antifungal regimen had been switched to and fro between liposomal amphotericin B and amphotericin B deoxycholate due to a fear of drug induced cholestatic jaundice from hospital day 21 until day 31 when polyene antifungals were halted completely after a recognition of A. terreus growth on every respiratory specimen. Intravenous and nebulized voriconazole and oral flucytosine via nasogastric tube were now chosen. Despite of therapeutic voriconazole levels in the range of 3.29–4.89 mg/L, pulmonary lesions were still growing in size with increment of serum GM to 9.73 and worsening respiratory parameters over a period of 10 days. A decision to switch treatment to intravenous posaconazole was made in view of potential SBECD accumulation. Plasma levels of posaconazole were measured to assure drug exposure adequacy. MICs of current A. terreus infection to voriconazole, posaconazole, caspofungin, anidulafungin, micafungin were 0.75, 0.125, 1, 0.004, and 0.064 mg/L, respectively.
Determination of posaconazole concentrations in plasma was performed using validated Ultra Performance Liquid Chromatography-Photo Diode Array (UPLC/PDA), according to the US Food and Drug Administration guidance for bio-analytical method validation []. Blood samplings for plasma posaconazole levels were performed dividing into two phases. The first phase took place when posaconazole 300 mg was given every 24 h, spotted plasma levels were obtained to determine the appropriate timing of the following doses in which resulted in a new dosing regimen of every 48-h interval. In the second phase happened when posaconazole 300 mg was given every 48 h, blood samples were collected for pharmacokinetic analysis at 0 h (predose), immediately at the end of infusion, approximately 15 min after the end of infusion, and approximately 4, 8, 12, 24 and 48 h after the start of infusion. After 34-day course of posaconazole with confirmation of therapeutic plasma posaconazole levels almost the entire period of time during posaconazole treatment (0.956–7.099 mg/L), his infection still did not subside. Serum GM prior to his death was 8.97. Autopsy result confirmed diffuse IA in his right lung without evidence of dissemination to other organs as well as no bacterial pneumonia documented. Additional immunological tests also declared impairment of natural killer T-cell function. Plasma posaconazole levels and serum GM are shown in Additonal file : Figure S1. An additional figure file shows summary of his clinical course [see Additional file ].
Liver function tests and QTc interval on electrocardiography data prior and during posaconazole treatment are displayed in Table . The findings demonstrated a decline in aspartate transaminase (AST) and alanine transferase (ALT) levels significantly after posaconazole use (p =0.005 and 0.028, respectively). On the other hand, there was an increase in alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) levels after posaconazole use with statistical significance (p = <0.001 and 0.039, respectively). There were no crucial changes on total bilirubin (TB), direct bilirubin (DB) and QTc interval. Statistical analyses on relevant parameters to compare the differences prior and during posaconazole therapy were performed using SPSS version 21.0 for Windows (IBM Corp., Armonk, New York). The distribution of continuous variables was determined by Kolmogorov-Smirnov test. All continuous variables were assessed by the Student's t-test or Wilcoxon Rank Sum test as appropriate. For normally distributed variables, data were described by mean ± standard deviation (SD). For skewed variables were described as median (range). A p value of less than 0.05 was considered significant for all statistic values.


A 73-year-old man was initially referred to the memory clinic in December 2013 with a history of gradual deterioration of short-term memory and increased dependence on family over an approximate 18-month period. This was with a background of stable multiple sclerosis with no other medical history of note. He was functioning well owing to a supportive family and positive routine activities undertaken mostly with his wife and had a strong academic background which could have contributed to masking of cognitive defects. He was given a diagnosis of a mild cognitive impairment based on impaired short-term memory, as evidenced by clinical evaluation and formal cognitive testing. He scored 80/100 on the Addenbrooke's Cognitive Examination III; most points were lost in the memory parts (where he scored 10/26) and less so in the fluency part (scoring 10/14) of the test. He was referred to neuropsychology, for brain imaging and was to be seen back in the clinic in 6 months' time. There were no treatable cardiovascular risk factors at this point; however, the patient was counselled on exercise and diet as well as basic activities to promote cognitive training in keeping with present guidance. The patient and his wife were informed it was difficult to give prognosis and although evidence is varied, a person with amnesic (memory loss) mild cognitive impairment would be at around 1 in 5 risk of being diagnosed with dementia at a later stage. From this presentation and clinical evaluation, it was thought that an Alzheimer's dementia was the most likely future diagnosis.
The patient then travelled by plane from Scotland to Australia, which involved a short connecting flight to London. On descent from the air to Australia, he experienced an episode of agitation and bizarre, nihilistic delusions about Nazis taking over the plane. After landing, he was admitted to a large, well-known teaching hospital in Australia. He continued to exhibit challenging behaviours such as agitation, wandering and resistance to attempts at basic care from nursing staff. The patient required assistance with feeding and one-to-one nursing care for the majority of the in-patient stay.
The patient's medical investigations included a positron emission tomography (PET) scan, magnetic resonance imaging (MRI) brain scan, lumbar puncture, electrocardiogram (ECG), chest X-ray, urinalysis, basic blood tests and whole-body computed tomography (CT) over the course of admission without an obvious cause being found for such a dramatic decline and previously unseen behaviours. Of note, any cerebrovascular accident, pneumocephalus, acute kidney injury, external and middle-ear disease and sepsis were ruled out on admission. It was noted that there were no particular risk factors in terms of family history, smoking, hypertension, dyslipidaemia and diabetes which could have increased the risk of most of the proposed diagnoses. Basic observations, including oxygen saturations, were largely unremarkable throughout his admission. He was reviewed by both the neurology and neuropsychiatric teams who came to a joint conclusion that he was experiencing a delirium and previously undiagnosed Alzheimer's dementia.
He was treated with antipsychotics and given a short trial of intravenous steroid given the history of multiple sclerosis (although not indicated by way of imaging) without any improvement in clinical state.
The patient stabilised enough for repatriation to the UK with a nurse escort after approximately 4 months of in-patient care. At this stage he showed significant deterioration in executive functioning from baseline assessment, limited capacity for new learning, confabulation and required assistance with all personal needs. On descent of the aircraft the patient again deteriorated, with disorientation, agitation and paranoid features once again predominant. Admission to hospital and further investigations gave us no obvious clues to an ongoing acute event. Brain imaging in both Australia and the UK remained unchanged with CT showing generalised atrophy and MRI revealing a minor degree of small vessel disease and smaller than expected hippocampal volume, and suggested Alzheimer's as the only radiological explanation for the presentation.
The episode has had a significant effect on the patient's level of functioning and a sizable knock-on effect on his family. He is now a patient in a National Health Service (NHS) long-term care facility requiring assistance with all basic activities of daily living and without much by way of coherent or meaningful conversation. He continues to be managed with antipsychotic medications and benzodiazepines which allow him to be settled on the ward and nursing staff to assist with his needs. It is difficult to ascertain whether there has been any further deterioration in the patient's disease process, however, there has not been any improvement seen. His family continue to harbour feelings of guilt at the original decision to fly to Australia without consultation with medical staff and disappointment at being unable to care for the patient in their home.
My overall aim for writing this case is for the reader to acknowledge the case of a patient with a likely dementia who has had a stark and accelerated decline in function as a result of a change in environment and residual delirium after going on two long-haul flights. Pinpointing the precise mechanism for the delirium continues to be a challenge owing to the number of medical staff involved and the difficulties with communication between continents. Prolonged hypoxia or changes in cabin pressure would seem to be the most obvious causative factors for the delirium given the collateral history, with particular focus on symptoms becoming pronounced on descent. However, this is without any firm scientific basis and is not backed up by anything discovered on clinical examination or investigation.


In 2002, the patient, a 64-year-old male, presented at the emergency room with severe thrombocytopenia and a self-limited intestinal hemorrhage of unknown origin and was diagnosed with chronic liver disease, Child A status. The cause of cirrhosis was attributed to alcohol consumption in the past. A bone marrow examination was performed and showed normal megakaryocytes, and as a result, hematological diseases were excluded. Thrombocytopenia persisted and was considered secondary to hypersplenism. The initial laboratory values are shown in Table , highlighting the severity of thrombocytopenia.
During the period 2005–2009, he suffered from repeated hemorrhages. Hence, he was treated with the first-line therapy which is IV IgG and prednisone. During these years, he needed emergency treatments and was hospitalized on several occasions. In spite of standard therapies, hemorrhages persisted but he did not develop liver decompensation.
In June 2009, he was hospitalized for ecchymoses, rectal bleeding, and severe thrombocytopenia requiring blood transfusions, IV IgG, and high doses of prednisone (1 mg per kilogram of body weight per day). A bone marrow exam was repeated, and no abnormalities were detected.
In August, October, and November 2009, he needed to be re-hospitalized for epistaxis and intestinal hemorrhage and his platelet count was 1.000–3.000 cells/mm3. Long-term high doses of prednisone, 100 mg/day, were administered from June 2009 to April 2010. Hemorrhages were clinically stabilized, but the patient's clinical situation deteriorated.
In November 2009, he was referred to our clinic for evaluation of his chronic liver disease. He had developed iatrogenic Cushing syndrome with cardiovascular complications (shortness of breath, swollen extremities, weight increase). Table shows the values of the patient's vital signs. General and specific analysis and abdominal doppler ultrasound were performed. Symptomatic treatment was established while tapering prednisone.
In March 2010, he started romiplostim treatment as a bridge for splenectomy. Taking into account his chronic liver disease and risk of vascular thrombosis, the target platelet count range was an average of 50,000–90,000 cells/mm3. Efficacy and safety were assessed weekly, during each visit. Figure shows the platelet count during this period.
In December 2010, prednisone was totally stopped and this allowed the patient to be considered for splenectomy. He was given an antipneumoccocal, meningococcal, and hemophilus influenzae vaccinations and underwent computed axial tomography (CAT) (Fig. ) and abdominal ultrasound test. In addition, a nuclear medicine study was carried out of the liver–spleen image with 99 mTc-labeled colloid, confirming enlarged spleen and a reduced platelet half-life with a pattern of increased splenic destruction.
In May 2011, open laparotomy with splenectomy was performed with a liver biopsy specimen obtained preoperatively, which showed advanced fibrosis without steatosis or other features. After the surgery, the patient showed full recovery.
Today, after 5 years of follow-up, the patient only requires vitamin supplements and standard ambulatory checkups every 6 months. His liver function remains stable, and platelet count is maintained at normal range.


The patient was a 47-year-old female who presented to the emergency department with acute headache and nausea/vomiting. She did not mention any previous history of severe headache or vomiting. On the neurologic examination papilledema was noted. There were no focal neurological deficits. She was dizzy but conscious and her Glasgow coma scale (GCS) score was 13. Computed tomography (CT) scan of the brain revealed enlargement of lateral ventricles and a well-circumscribed hyperdense mass on the roof of the third ventricle at the location of foramen of Monro (). On MRI examination, a hyperintense rim was seen around lateral ventricle on FLAIR sequence that was compatible with interstitial edema and acute nature of hydrocephaly (). A T2-hypointese (), T1-isointense mass was seen on the roof of the third ventricle (). The characteristic location and MRI signal intensity were consistent with colloid cyst. Blooming artifact was visible on susceptibility weighted sequence () and suggested the hemorrhagic nature of the lesion and explained the occurrence of acute hydrocephaly.
The patient underwent ventriculostomy followed by craniotomy and tumor resection and experienced an uneventful recovery. Histological examination confirmed the diagnosis of hemorrhagic colloid cyst.


A 24-year-old female patient woman was admitted to our hospital complaining of abdominal pain, loss of appetite, fever, headache, a weight loss, nonproductive cough and menstrual irregularity. Her symptoms started three weeks earlier and she was treated with antibiotics and steroids for Erythema nodosa and Polyarthritis. She had a positive family history for tuberculosis since her father had died two years ago from Pulmonary TB.
At admission, the patient was febrile, intoxicated, hypotensive, anemic, no palpable lymph nodes were noted, normal heart sounds, lungs with rales bilaterally, blood pressure was 90/60 mmHg, respirations 24/min, Pulse 80 beats/min, enlarged liver and spleen, with dolente tenderness in lower left abdominal quadrant, meningeal sings were negative and the rest of physical examinations were normal.
From laboratory analysis revealed elevated ESR = 40/, HB = 8.7 g/dl, leucocytes = 5.2 × 109/L, CRP = 48, liver enzymes, urea, glucose and kreatinin in normal levels, total proteins = 64 g/L, albumins = 36 g/L, LDH = 492 U/L, Fe = 8.6 mmol/L, blood cultures sterile, Wright negative, Widal negative. Chest x rays bilateral adenitis as shown in Fig., Mantoux probe 15 mm, HIV negative, serum CA 125 = 1430…1455, CA 19-9, AFP, CEA and CA 15-3 in normal levels. Ultrasound and MRI of abdomen revealed cystic formation on left tubo-ovarial complex and ascites as shown in Figs. and .
Abdominal paracentesis was performed and revealed clear exudative fluid with benign cells. In consultation with gynecologist, the patient underwent operation, suprapubic transversal laparotomy. During operation, in the left tubo-ovarial complex was found caseose mass which was sent together with samples from omentum, peritoneum and ascites for histopathology and microbiological examination. On histopathological examination were seen epiteloidal granulomas with gigantic multinuclear cells, lymphocyte infiltrations and caseous necrosis. On Lowenstein-Jensen cultures was isolated Mycobacterium tuberculosis sensitive to Rifampicin (RIF), Izoniazid (INH), Ethambutol (ETH) and Streptomycin (STM). The patient was treated with a 4-drug TB treatment regimen consisting of RIF, INZ, Pyrazinamide, and ETH for the first two months and with two antituberculotics (RIF and INH) for another 7 months and recovered completely. Her serum cancer antigen 125 level was elevated for three months.


A 41-year-old Sri Lankan man presented to our unit with progressive abdominal distension and discomfort for 3 months. He also noticed loss of appetite and loss of weight for the same period of time. There was no history of sudden epigastric or right hypochondrial pain, hematemesis, melena, per rectal bleeding, or altered bowel habits. Nor did he have any confusion or altered sleep pattern suggestive of hepatic encephalopathy. He was previously well with no prior diagnosis of diabetes mellitus, hypertension, or dyslipidemia. He was abstinent from alcohol and he was not a tobacco smoker; he denied any intravenous drug abuse, blood transfusions, sexual promiscuity, or past history of hepatitis. There was no family history of liver diseases or HCC.
On examination, he was not icteric or pale and there was no bilateral leg edema or peripheral stigmata of chronic liver cell disease. His cardiovascular system examination was normal with a normal blood pressure. His abdomen was distended with a palpable irregular mass in the left lobe of his liver without a bruit. There was no splenomegaly. A moderate amount of free fluid was present. A neurological examination revealed no signs of hepatic encephalopathy.
Initial basic investigations showed anemia and leukocytosis with normal liver and renal biochemistry (Table ). His blood picture showed normochromic normocytic anemia with mild to moderate rouleaux formation and mild neutrophilic leukocytosis. His inflammatory markers were high with an erythrocyte sedimentation rate (ESR) of 125 in the first hour and a C-reactive protein (CRP) of 155 mg/L (<6). His urine full report was normal. His fasting blood sugar (5.4 mmol/L) and lipid profile were normal. His lactate dehydrogenase (LDH) was 669 U/L (230 to 460) and amylase was 68 U/L (22 to 80).
Hepatitis B serology (hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody) and hepatitis C serology (HCV antibody and hepatitis C ribonucleic acid (RNA)) were negative as were human immunodeficiency virus (HIV) serology and Venereal Disease Research Laboratory (VDRL) test. Serum iron studies were within normal range except for marginally elevated serum ferritin (Table ). His serum alpha-fetoprotein was 12 μg/L. The result of an antinuclear antibodies (ANA) test was negative and the ceruloplasmin level in the serum was normal.
An ultrasound (USS) scan of his abdomen showed a heterogeneous ill-defined area of 4.5 × 2.4 cm in the left lobe of his liver with irregular margins. The rest of his liver was normal with normal outline and uniform echogenicity without features of cirrhosis. His gall bladder and bile ducts were normal. His spleen was mildly enlarged (12.6 cm) and moderate ascites was present. A portal vein Doppler showed normal flow pattern with no evidence of portal vein thrombosis (portal vein diameter 0.98 cm and flow velocity 25 cm/second). There was no para-aortic lymphadenopathy. His pancreas, kidneys, and prostate were normal. A posteroanterior chest X-ray (CXR-PA) showed elevation of his right hemidiaphragm (Fig. ).
Contrast-enhanced triple-phase computed tomography (CT) showed a 7.5 × 6.5 cm lesion in the left lobe of his liver which enhanced during the arterial phase and showed a washout effect in the venous phase (Fig. shows liver lesion seen at 30 seconds from contrast administration, delayed film; Fig. shows liver lesion seen at 70 seconds, delayed film; and Fig. shows liver lesion seen in 5 minutes, delayed film). The right lobe of his liver was normal. Intrahepatic and extrahepatic ducts were normal. There were no para-aortic masses. Gross ascites was evident (Fig. ).
A diagnostic peritoneal tap revealed the ascitic fluid to be slightly turbid and mildly blood stained. His ascitic fluid albumin was 40 g/L (serum-to-ascites albumin gradient = -03 g/L) and it contained 25 neutrophils/mm3, 160 lymphocytes/mm3, and 4000 red blood cells/mm3. His glucose concentration was 4.0 mmol/L: random blood sugar (RBS) 7.0 mmol/l. His adenosine deaminase level was 29 U/L: tuberculosis (TB) 92 +/– 45, non-TB 12 +/– 11. An analysis of 200 mL of ascitic fluid for cytology showed reactive mesothelial cells, histiocytes, and lymphocytes. There was no evidence of atypical cells. A Gram stain and bacterial cultures of ascitic fluid were negative. Polymerase chain reaction (PCR) and culture for TB were also negative.
Laparoscopic assessment revealed gross ascites, peritoneal deposits (Fig. ), and omental deposits (Fig. ) with bowel adhesions. Ascitic fluid was drained and cytological analysis of 500 mL was negative for malignant cells. A liver lesion was seen at the left lobe of his liver (Fig. ) and biopsies were taken from the liver lesion as well as omental and peritoneal deposits. TB culture, TB PCR, and GeneXpert for Mycobacterium tuberculosis in material retrieved from the liver lesion, omental deposit, and peritoneal deposit were negative. The biopsy from his liver showed nests and trabeculae of cells with vesicular nuclei and prominent nucleoli with sinusoidal pattern focally. Cytoplasmic bile staining and intranuclear inclusions were not seen. A biopsy from his peritoneum and omentum showed nests of similar cells infiltrating the desmoplastic stroma. These findings supported a diagnosis of HCC which was confirmed by immunohistochemistry.
He refused any surgical or oncological interventions and wished to be managed conservatively. He died 3 months later.