A 55-year-old woman with a history of type 2 diabetes mellitus, hyperlipidemia, obesity, and depression was referred to an endocrinologist with complaints of weight loss, palpitations, and diarrhea. The patient also had hypertension and was taking α-adrenergic receptor antagonists and a calcium channel blocker. She was found to have a thyroid-stimulating hormone (TSH) level of <0.10 (normal: 0.34 to 4.82) µlU/ml and a free T4 concentration of 4.28 (normal: 0.6 to 1.6) ng/dL. I123 thyroid scan revealed elevated, diffuse uptake bilaterally, without nodules, consistent with the diagnosis of Graves' disease. The patient was treated with 11.9 mCi of radioactive iodine. Ten days after the ablation treatment, the patient presented to a local hospital by ambulance after experiencing lightheadedness, diffuse abdominal pain, and one episode of bilious emesis.
Upon arrival, she was hypotensive (77/44 mm Hg), pale, bradycardic, and febrile (39.4°C). An electrocardiogram (ECG) revealed accelerated junctional rhythm at a rate of 53 beats/min. The patient was given atropine 0.5 mg intravenously without effect, followed by initiation of external cardiac pacing. Continuous intravenous infusions of dopamine and norepinephrine were started along with fluid resuscitation of 4 L of normal saline over a 2-hour period. She received one ampule of calcium gluconate with no change in her blood pressure, heart rate, or rhythm. Computed tomography of the abdomen was unrevealing. The patient was endotracheally intubated and transferred via helicopter to our facility.
Upon arrival to our facility, she was receiving intravenous infusions of dopamine at 20 µg/kg/min and norepinephrine at 10 µg/kg/min and remained hypotensive (92/55 mm Hg) and bradycardic (59 beats/min). ECG showed an accelerated junctional rhythm. Laboratory findings included serum sodium of 139 mEq/L, potassium of 5.3 mEq/L, chloride of 108 mEq/L, and total CO2 content of 15 mmol/L, serum glucose of 208 mg/dL, urea nitrogen of 38 mg/dL, creatinine of 1.5 mg/dL, ionized calcium of 1.15 mmol/L, total bilirubin of 0.4 mg/dL, serum alkaline phosphatase of 141 U/L, aspartate aminotransferase of 2196 U/L, and alanine aminotransferase of 2010 U/L. Plasma troponin I was repeatedly undetectable. The peripheral leukocyte count was 15.9 x 109 cells/L with no immature forms. There was evidence of an anion gap metabolic acidosis with a serum lactate concentration of 6.2 mmol/L. Blood cultures revealed no microbial growth. Thyroid function testing showed an undetectable TSH (<0.10 µlU/ml), a free T4 of 12.8 (normal: 0.6 to 1.6) ng/dL, total T4 of 21.9 (normal: 5.6 to 13.7) µg/dL, and a total T3 of 0.94 (normal: 0.8 to 1.8) ng/mL. The patient was treated for thyroid storm with 1000 mg of propylthiouracil by orogastric tube as a loading dose followed by 300 mg every 6 hours, 5 drops saturated solution of potassium iodide (SSKI) every 8 hours by orogastric tube, and 100 mg intravenously of hydrocortisone every 8 hours. The hypotension resolved, vasopressors were stopped, and the patient was extubated 25 hours after her initial presentation. During her stay in the intensive care unit, the patient exhibited fever (39.6°C maximum), tachycardia, and tremulousness. These manifestations resolved over a period of 22 hours. The patient was discharged in satisfactory condition on the fourth day of hospitalization on 100 mg of propylthiouracil orally every 8 hours. Outpatient testing days later demonstrated normalization of her thyroid function tests.


A 24-year-old male presented with photophobia since birth. No family history for colour vision defects or retinal dystrophies was reported. Myopia with an refractive error of − 5.50 D (right eye) and − 6.50 D (left eye) and astigmatism were found in the patient (III:2) at the age of 8 months along with nystagmus but devoid of strabismus. Glasses were given at the age of 1 year. Difficulties distinguishing colours were noticed by his parents at the age of 3 years. Achromatopsia was the first suspected diagnosis. At the age of 4 years occlusion therapy alternating in both eyes for 2 months was attempted to treat amblyopia but was unsuccessfull. A best-corrected visual acuity of 20/200 was measured with Snellen charts at the age of 6 years. No brain injuries were detected by magnetic resonance imaging. Visual evoked potential flash and B-scan ultrasonography performed normal for both eyes. At the age of 11 years a visual acuity of 20/250 was measured. At the latest exam at the age of 24 years, full-field light- and dark-adapted electroretinogram (ERG) recordings were performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocol []. Subnormal amplitudes under scotopic conditions and extinct responses under photopic conditions were observed in both eyes of the patient (III:2) in comparison to normal controls (Fig. ). A visual acuity of 20/400 was measured for both eyes with a myopic correction of − 12.00 D (right eye) and − 11.50 D (left eye). Anterior segment, pupillary reflexes and intraocular pressure revealed no abnormalities. Eye fundus examination revealed normal retinal vessels, optic nerve heads showing tilted optic discs with myopic conus and the maculae had elapsed reflex without waxy reflex (Fig. ). Spectral domain optical coherence tomography (SD-OCT) performed with Spectralis OCT (Heidelberg Engineering) showed normal retinal architecture with thinned photoreceptor layer (Fig. ). Colour vision test evaluated with the Farnsworth D-15 Colour Test revealed protan-deutan confusion errors (Fig. ).
Mutation screening of OPN1LW/OPN1MW gene cluster in the patient (III:2) was performed as previously described []. Genotyping PCRs with genomic DNA from the patient (III:2, see Fig. for a pedigree of the genetically investigated family members) revealed absence of the LCR and promoter regions of both OPN1LW and OPN1MW genes – indicative for a large deletion – but presence of the 3′ parts of the OPN1MW gene, namely exons 4, 5 and 6. Upon fine sequence tag site content mapping, the deletion was finally bridged with a PCR amplicon performed with primers BCM#27_F (5′- TCGACCCAGAATTAACCTCTCT -3′) and BCM#27BPR (5’-TCTAAAAATGGACAAGGATTAACCA -3′) which was sequenced with Sanger to determine the exact breakpoints in patient III:2 (Fig. and Fig. ). The deletion, NC_000023.11:g.154,118,184_154,191,311del, encompasses 73,128 bp with the centromeric breakpoint located in the intergenic region between MECP2 and OPN1LW and the telomeric breakpoint within intron 3 of OPN1MW (Fig. ).
A sequence alignment of the breakpoint junction sequence in the patient (III:2) with the corresponding non-mutant sequence sections from his grandfather (I:1) revealed an overlapping stretch of 13 bp between the centromeric and the telomeric breakpoint sequences (Fig. ) shared by two Alu elements. The sequence remnants embedded within the deletion breakpoints resembled the junction of two Alu elements; (1) a fossil right Alu momomer (FRAM) element at the centromeric breakpoint of the deletion, and (2) an AluJo element in intron 3 of OPN1MW at the telomeric breakpoint of the deletion (Fig. ). Microsatellite marker analysis revealed that the X-chromosome present in the patient (III:2) had been transmitted from his maternal grandfather (I:1, Fig. ). Segregation analysis performed by means of breakpoint PCR amplification showed that neither the patient’s grandfather (I:1) nor the mother (II:1) carry the deletion (Fig. ). The CARE guidelines were followed in reporting this case.


A 70-year-old man underwent an endoscopic examination owing to epigastric pain and was diagnosed with esophageal cancer. The endoscopic examination revealed an irregular mucosa in the lower esophagus, and biopsies confirmed squamous cell carcinoma. Contrast-enhanced CT did not depict the esophageal lesion but showed enlarged lymph nodes in the tracheal bifurcation and bilateral hilum of the lung. FDG-PET/CT revealed abnormal accumulation in the main tumor in the lower esophagus (maximum standardized uptake value [SUV max]: 4.06) and higher accumulation in the hilar-mediastinal lymph nodes (SUV max: 15.0) and enlarged mediastinum lymph nodes (SUV max: 6.94) (Fig. ). The primary lesion of the esophagus was staged T1; nevertheless, it was still difficult to rule out metastasis in the lymph nodes. We selected chemotherapy as the first-line treatment. The patient was administered 2 cycles of 140 mg cisplatin and 1400 mg 5-fluorouracil over 2 months. In each cycle, 9.9 mg dexamethasone was administered to prevent side effects of chemotherapy. Subsequently, we observed a disappearance of the FDG uptake in the primary lesion, and a slightly reduced FDG uptake in the mediastinal and bilateral hilar lymph nodes (Fig. ). These non-identical responses to chemotherapy did not indicate cancer metastasis, but most likely a sarcoid-like reaction of the lymph nodes associated with squamous cell carcinoma of the esophagus. Therefore, the patient underwent video-assisted thoracoscopic surgery esophagectomy (VATSE) with gastric tube reconstruction via the retrosternal route. The pathological diagnosis was moderately to poorly differentiated squamous cell carcinoma of the lower thoracic esophagus. The resected lymph nodes demonstrated no tumor metastasis. However, some lymph nodes (#8a, #106RecR, #107, #108, #109) showed granulomatous reactions, histiocytes, multinucleated giant cells, and scar-like fibrosis (Fig. ), suggesting the presence of sarcoidosis or sarcoid-like reactions. In accordance with the Union for International Cancer Control (UICC) TNM staging system (7th edition), the tumor was classified as pT1N0M0, pStage IA. The patient was discharged 49 days after surgery. FDG-PET/CT performed 15 months after surgery showed bilateral FDG accumulation in the hilar lymph nodes without tumor recurrence.


A 72-year-old woman with a past medical history of sarcoidosis underwent an endoscopic examination owing to dysphagia. The endoscopic examination revealed a circumferential tumor with ulceration in the cervical esophagus. Biopsies obtained during the endoscopy indicated squamous cell carcinoma. Contrast-enhanced CT showed extensive tumor growth with suspected tracheal invasion and enlarged lymph nodes extending from the cervical region to the upper mediastinum. FDG-PET/CT revealed abnormal FDG accumulation in the primary lesion (SUV max: 23.1) and lymph nodes (SUV max: 5.45) from the cervical to upper mediastinal region (Fig. ). However, it was difficult to determine whether the multiple lymphadenopathy was benign or metastatic because of her past medical history of sarcoidosis. Therefore, and also for the purpose of preserving the larynx, we initiated definitive chemoradiotherapy. The patient was administered 2 cycles of 45 mg cisplatin and 700 mg 5-fluorouracil with 60 Gy/30 fr radiation therapy over 2 months. In each cycle, 8 mg dexamethasone was administered to prevent side effects of chemotherapy. After completing the chemoradiotherapy, we observed complete disappearance of FDG uptake in the primary cancer in the esophagus, and only a slight reduction in FDG uptake in the mediastinal lymph nodes (SUV max: 3.26; Fig. ), which indicated that the lymph nodes were affected by sarcoidosis. The primary lesion of the esophagus relapsed 3 months later. Then, the patient underwent thoracoscopic and laparoscopic total laryngopharyngoesophagectomy with gastric tube reconstruction via the posterior mediastinal route. The pathological diagnosis was moderately differentiated squamous cell carcinoma in the cervical esophagus. The resected lymph nodes demonstrated no tumor metastasis. However, some lymph nodes showed granulomatous reactions and contained several small epithelioid cell granulomas (Fig. ), suggesting the presence of sarcoidosis. The final stage was determined as pT2N0M0, pStage IB (UICC 7th). The patient was discharged 27 days after surgery. Contrast-enhanced CT performed 6 months after surgery showed no tumor recurrence. However, the patient died of myocardial infarction 1 year after surgery.


We present a 30-year-old female patient, who was admitted with low back pain and generalized body ache for 2 months prior to presentation; it was excruciating pain especially during nighttime and not much relieved by simple analgesics. The patient has a history of poor appetite with weight loss of about 4-5 kg in a span of 3 months, otherwise had no pulmonary symptoms. She is a nonsmoker and has no past medical illnesses.
Upon physical examination, the patient had bilateral discrete small cervical and axillary lymphadenopathy, and the breast examination was normal. Other systemic examination was not significant.
During routine workup in emergency, a chest X-ray was done, which was suggestive of bilateral fluffy hilar opacities (), and a CT thorax was done (Figures and ), which was suggestive of scattered areas of multifocal consolidation noted in the left lung and areas of scattered mosaic perfusion noted in the subpleural region, small nodules are also noted in the right lung, and both hila are prominent. The bone window shows multiple sclerotic bony lesions in the vertebra of variable sizes. There is no evidence of any collapse of the vertebra. The spinal canal diameter is normal. No spinal canal stenosis was seen.
Blood investigation showed normal CBC, electrolytes, urea, creatinine, and calcium, ESR was elevated 50 mm/hr, and high alkaline phosphatase (ALK) (224 U/L; normal 40–150 U/L), and other bone tumor markers were not done as not available.
Ultrasound (US) neck showed bilateral cervical lymphadenopathy; right-side nodes are noted, the largest of which measures 21 × 10 mm in size. Left-side nodes are noted, the largest of which measures 12 × 9 mm in size, and US breast examination was normal.
Whole-body PET scan () showed progressing pulmonary consolidations and nodules compared to the CT, multiple osseous involvements, generalized, metabolically active lymphadenopathy involving supra- and infradiaphragmatic regions, and hepatomegaly with solitary hepatic lesion.
Axillary lymph node biopsy was done, and the histopathology finding is most consistent with metastatic lung adenocarcinoma. The immunohistochemical (IHC) profile is most consistent with lung primary. Breast, ovary, and biliary tract are excluded by additional IHC with appropriate controls, which is positive for Napsin A and is negative for GATA-3.
Patient was referred to Cancer Centre for further plan of management. Patient started on chemotherapy with crizotinib 200 mg BID and denosumab 120 mg·q 4 weekly subcutaneous with good response according to the new PET scan (). As compared to the previous PET scan 7 months before, there is favorable treatment response, metabolic resolution of previously seen left lung uptakes and lymph nodes above and below the diaphragm and metabolic resolution of bone metastases with increasing sclerosis also denoting favorable response.


37-year-old woman presented to the emergency room with headache. Bilateral pelvic sensitivity and a mass painful to touch in a plastic texture that filled the Douglas' pouch were detected during the examination; the mass was evaluated in favor of leiomyoma. ß-hcg was negative, wbc was 9800/mm3, hgb was 12 g/dl, htc was 35%, plt was 282000/mm3, and no unusual characteristics was found in complete urinalysis. Ultrasonography revealed a mass consistent with a degenerated myoma measuring 77x82mm, of which subserous component was greater in the posterior wall and endometrial thickness was 7-8 mm, which was concordant with the cycle. The left ovary of the patient was normal, but since the right ovary could not be fully evaluated, computerized tomography (CT) was requested for possible adnexal pathologies. CT demonstrated a hypodense nodular lesion with a diameter of 75 mm that extended to the right adnexal region and MRI with contrast was performed on the patient. MRI revealed a mass with a hypovascular appearance following a heterogeneous and hypointense IV contrast material with a diameter of 8 mm, which appeared to displace the posterior cervix.
It is seen that myoma included by central necrosis depleted by cervix in the posterior part of the uterus. Also the development of necrosis was seen and myomatosis was evaluated in favor of degeneration ().
In addition, since the patient's pain regressed spontaneously during the follow-up, surgical operation was postponed to perform in elective conditions. After making necessary preparations for the operation, laparoscopic myomectomy was performed. Myoma was not considered suspicious apart from being degenerated. It was removed by morcellating in an isolated bag (Figures , , , and ).
No complication or hemorrhage occurred during surgery. As there was not any problem observed during the post-op follow-up, the patient was discharged from the hospital on condition that the pathology report was brought on the second day of post-op. The subsequent report revealed marked cellularity and pleomorphism, extensive necrosis, mitosis >5/10BBA, KI67 proliferation index >%50, weak positivity for p53, and LMS with no detectable lymphovascular invasion.
The patient was informed about the pathology report and interned again to perform transabdominal hysterectomy and bilateral salphingoopherectomy. The pathology report revealed “atypical pleomorphic fusiform cell proliferation area” measuring 3x2 mm in a focal area within the cavity consistent with residual LMS when evaluated together with laparoscopic myomectomy material.
To follow-up the patient was referred to radiotherapy and medical oncologists. After 3 months from her 1st surgery, positron emission tomographic scan (PET-CT) was performed and fluoro-2-deoxyglucose (FDG) uptake is noted in the area above rectosigmoid mesentery towards the left abdominal wall in pelvic floor ().
She was referred to gynecologic oncologist and 3rd operation was performed. A mass about 4-5 cm of size in defined localization was excised; there were not any other mass and lymphadenopathy detected during the surgery. The pathology result was high grade malign mesenchymal tumor with high cellularity, extensive necrosis, mitosis 40/10 BBA, and moderate atypia. There was no tumor in surgical margin. She is now being followed up by the gynecologic oncologist with appropriate medical treatment.


A 75-year-old Caucasian woman, gravida 5, para 3 with past medical history of hypertension, rheumatoid arthritis, and chronic obstructive pulmonary disease arrived to the emergency department looking for relief from dental pain. Neither initial exam nor maxillary plain film showed evidence of cause for facial pain, and she was admitted for further evaluation and pain control. On reevaluation, she was noted to have diplopia and facial droop, so MRI brain along with MRI/MRA of head and neck with and without contrast was ordered to rule out cerebrovascular accident (CVA). CVA was ruled out; however bone marrow lesions involving the left and the right clivus, right Meckel's cave, and posterior margin of the right cavernous sinus were noted ().
CT scans of chest, abdomen, and pelvis with and without contrast were ordered to search for primary malignancy. These studies revealed homogeneous enhancement of the uterus concerning for diffusely infiltrative endometrial carcinoma with associated relatively bulky retroperitoneal adenopathy of the abdomen and bilateral iliac chain adenopathy. In addition, multiple pulmonary nodules were noted along with L sided neck, mediastinal, and right hilar adenopathy ().
Cervical biopsies were obtained disclosing LCNEC of the cervix (). The tumor cells were immunoreactive for neuroendocrine markers synaptophysin and chromogranin. They were also immunoreactive for pancytokeratin and p16, the latter a surrogate marker for the presence of high-risk HPV often seen in these cervical carcinomas. The tumor cells lacked immunoreactivity for estrogen receptors and p63.
She was diagnosed with stage IV LCNEC with distant metastasis. This patient went on to receive palliative radiation to her brain for symptom control and was scheduled to see oncology as an outpatient to discuss treatments. However, due to decline in functional and mental status, she was no longer a candidate for chemotherapy and comfort care was pursued. She died 2 months after diagnosis.


A 12-year-old girl presented to her general pediatrician complaining of asthenia and weight loss in the previous month. Her past medical and family history were unremarkable. Physical examination revealed a painless hepato-splenomegaly without additional clinical signs. Abdominal ultrasound revealed an inhomogeneous liver appearance, abdominal lymphadenopathy and a hypo-echogenic solid neoformation in front of the celiac artery (35 × 13 mm). The patient was admitted to the Department of Pediatrics of the Meyer Children’s Hospital for further diagnostic investigations.
Physical examination revealed palpable spleen and liver, a right inguinal lymph node of 1 cm and a lymph node in supraclavicular location, without any further objective anomaly. She had no fever. Initial laboratory tests found microcytic iron deficiency anemia (Hb = 9.8 g/dl, MCV = 65.5 ft., Ferritin = 4 ng/ml), with normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), normal total protein and protein electrophoresis, a slight increase of lipase and colic acids with normal amylase. Blood biochemistry for kidney and liver function and urinalysis were normal. Primary immunologic work-up including lymphocyte subset and immunoglobulin levels were normal. Tests for malignancies (tumor markers and peripheral blood smear) and infectious investigations, including Mantoux Test and IGRA Assay resulted negative.
Chest X-ray was negative. Magnetic resonance imaging (MRI) examination of the superior and inferior abdomen with contrast medium confirmed increased liver dimensions and its structural inhomogeneity with zones of signal alteration: some nodular, other confluent. It also revealed increased spleen size with zones of nodular signal alteration and multiple nodular formations in the following locations: hepatic hilar, mesenteric, lombo-aortic, at the retrocavity of the epiploon, and the greatest one in front of the celiac artery (diameter > 3.5 cm).
Suspecting a systemic lymphoproliferative disease, we performed liver and lymph node ultrasound-guided biopsy, which showed negativity of Polymerase chain reaction (PCR) for potential agents of infectious diseases (including Mycobacteria and Bartonella species) on lymph node material, while it highlighted a non-necrotizing granulomatous inflammation, resembling sarcoidosis, and aspects of non-specific inflammation of the liver. (Fig. , ).
Subsequently, we carried out measurements of serum and urinary calcium, serum phosphorus, Angiotensin-Converting Enzyme (ACE), followed by a complete cardiac evaluation, and a complete ophthalmologic evaluation (including slit lamp), all of which resulted within normality.
At this point, given the biopsy results, we performed further lung studies: pulmonary function tests which showed mild restriction and decreased alveolar capillary diffusion. The chest X-Ray revaluation revealed a pattern compatible with mild fibrosis and enlarged lymph nodes. We decided to carry out a high-resolution chest computed tomography (CT), which showed widespread fibrous strands and multiple enlarged lymph nodes (right paratracheal area, at the supraaortic trunk origin, subcarinal, with the largest in this location measuring 30 × 17 mm, pericardiophrenic, bilaterally at axillary level and along the mammary vessels). The bronchoscopic investigation with analysis of the broncho-alveolar lavage (BAL) fluid revealed: macrophages 70%, neutrophils 4% and lymphocytes 26% with a CD4/CD8 ratio of 9.2 (pathological value > 3.5).
Based on these results, we carried out further investigations on liver tissue and lymph node with histochemical techniques: CD68 + nodules were found, suggestive of microgranulomas (Fig. and ).
Having ruled out other diagnoses, with suggestive histological findings in two different tissues (liver and lymph nodes) and considering lung involvement, we made the diagnosis of pediatric-onset adult sarcoidosis.
During hospitalization, the condition of the child had always been good and she had always been afebrile. Considering lymph node hypertrophy and the signs of initial portal hypertension (due to compression of the hepatic vessels), we started therapy with prednisone 40 mg/day, and subsequent cross-therapy with mycophenolate mofetil (250 mg/m2 increasing up to 1 g/m2).
The girl came back to our attention a month after discharge for a follow-up visit: she was found in good general condition, with hepatomegaly and without other clinical signs or symptoms. A brain MRI was performed in order to rule out cerebral involvement and it revealed normal findings. One year later she maintained good clinical condition and normal laboratory tests, therefore MMF was gradually reduced and definitively suspended after 18 months. Now her periodic follow up consist of clinical and laboratory evaluation every 6 months and annual pulmonary function tests, unless clinical or laboratory new findings.


A 62-year-old Caucasian man, nonsmoker, had recto-sigmoid carcinoma in September 2015. Initial investigations showed the cancer was T3, N2 and M0 (grade II adenocarcinoma). He received neoadjuvant chemoradiotherapy with Capecitabine and radiotherapy (50Gy in 25 fractions) which was completed in December 2015.
Post chemo-radiotherapy, computed tomography (CT) scan and positron emission tomography (PET)/CT showed favourable rectal tumour response, but there were six small new liver lesions on magnetic resonance imaging (MRI). He was started on Modified De Gramont regimen plus Oxaliplatin in March 2016, Panitumumab was added in May 2016 as K-RAS was wild-type. Reassessment CT scan, MRI and PET scans in September 2016 showed a very good response in the liver and rectal primary lesions with no evidence of extra-hepatic disease. Only two lesions had been identified in the liver MRI while the rest of the lesions disappeared (). He underwent resection of the rectal disease with loop ileostomy by end of January 2017. The postoperative pathology showed a complete response. After recovery from bowel surgery, he continued on systemic chemotherapy and Panitumumab early March 2017 for three more cycles.
In May 2017, he was admitted with a 3-day history of fever, dry cough, progressive shortness of breath and decreased exercise tolerance. SpO2 was reduced at 88%. The total number of Panitumumab treatment cycles the patient received prior to this acute admission was 18.


A 54-year-old male with a history of non-ischemic cardiomyopathy (left ventricular ejection fraction of 20%), atrial fibrillation, hypertension, and insulin-dependent diabetes mellitus presented with lethargy and confusion. His home medications included aspirin, glimepiride, duloxetine, gabapentin, insulin glargine, prasugrel, furosemide, sotalol, rivaroxaban, and spironolactone. He also did not have a history of tobacco, alcohol, or illicit drug use.
He had a prior hospitalization for orthostatic hypotension and was eventually discharged to a skilled nursing facility but returned to the hospital three days later with an acute change in his mental status. On presentation, he was noted to have a respiratory rate of 26 breaths per minute, a heart rate of 62 beats per minute, blood pressure of 121/73 mmHg, a temperature of 37°C, and oxygen saturation of 97% on room air. The laboratory investigation revealed thrombocytopenia of 35 k/mcL as compared to 137 k/mcL three days earlier. Further workup was significant for an anion gap of 40 and LA of 18.7 mmol/L (reference range (ref) 0.5 - 2.0 mmol/L). He had also developed acute renal injury with creatinine of 1.9 mg/dL (ref 0.70 - 1.50 mg/dL). Liver enzymes were also elevated with aspartate aminotransferase (AST) of 254 U/L (ref 17 - 59 U/L), alanine aminotransferase (ALT) of 180 U/L (ref 21 - 72 U/L), and total bilirubin of 1.9 mg/dL (ref 0.2 - 1.2 mg/dL). Sepsis bundle was initiated with intravenous (IV) fluids and broad-spectrum antibiotics as well as microbial cultures, including the collection of two sets of blood cultures.
Additional investigation showed that lactate dehydrogenase was 1472 U/L (ref 110 - 216 U/L) but haptoglobin was normal: 85.9 mg/dL (ref 16 - 200 mg/dL). His hemoglobin was 6.4 g/dL (ref 14 - 17.4 g/dL), requiring blood transfusions while he also developed leukopenia; absolute neutrophil count (ANC) was 670. Due to his change in mental status associated with thrombocytopenia, anemia, and renal injury, there was a concern for thrombotic thrombocytopenic purpura (TTP). The peripheral blood smear demonstrated decreased platelets and an absence of schistocytes or blasts, but it did show numerous smudge cells and a few nucleated blood cells. ADAMTS-13 was 98 (ref >66 %) ruling out TTP. A computed tomography (CT) scan of the chest, abdomen, and pelvis only revealed an enlarged liver and moderate splenomegaly but did not show any lymphadenopathy.
Although his presentation was considered likely from sepsis, as his condition continued to deteriorate, hemophagocytic lymphohistiocytosis (HLH) was also considered. He met four out of five criteria for HLH with a ferritin of 9374 ng/mL (ref 20 - 300 ng/mL) cytopenia, fever, and splenomegaly. However, his serum triglyceride was 244 mg/dL, which is lower than 265 mg/dL, the criteria needed for HLH. As the patient continued to deteriorate with worsening lactic acidosis (Figure ) despite broad-spectrum antibiotics, thiamine administration, and continuous renal replacement therapy (CRRT), a bone marrow biopsy was performed to evaluate for marrow erythrocytic phagocytosis. He was also started on the HLH treatment protocol, receiving dexamethasone. Cyclosporine was initiated the next day, followed by etoposide. He developed multiorgan failure with persistent encephalopathy, despite discontinuing all sedation, coagulopathy, worsening liver enzymes, and cytopenia. Serum LA remained elevated with a minimum value of 14.9 mmol/L during his seven-day hospital course (Figure ) and arterial blood pH varied from 7.15 to 7.25.
A bone marrow biopsy showed that hemophagocytosis was not identified. The bone marrow contained a monomorphic cellular infiltrate with areas of necrosis and cellular degeneration. Less than 10% of the marrow appeared fully viable and contained a monomorphous infiltrate of cells with irregular nuclear contours and pale cytoplasm. The infiltrate was positive for CD45, CD20, and CD79a, and negative for CD34, with patchy non-specific staining for TdT. The Ki67 (MIB-1) proliferation rate was up to 60%. The absence of CD34 and a convincing TdT expression favored large B-cell lymphoma. The disease was classified as Ann Arbor stage IV due to its presence in the extra-lymphatic organs (liver and bone marrow). The age-adjusted international prognostic index (IPI) score was calculated to be 3, conferring high risk.
Chemotherapy regimen “R-CHOP” for this diagnosis of diffuse large B-cell lymphoma (DLBCL) was planned with a few variations. As rituximab is dialyzed, it was not administered because he required CRRT and vincristine was held due to its hepatotoxicity on already deranged liver enzymes. Steroids were changed to IV methylprednisolone. Doxorubicin was also initiated followed by cyclophosphamide and etoposide while cyclosporine was discontinued. Unfortunately, his condition continued to deteriorate, and he became bradycardic and hypotensive, eventually requiring multiple vasopressors. After discussions with the family, comfort measures were pursued.


A 25-year-old woman was referred to our radiology department by her family doctor for an MRI examination of the left knee because of a “crackling” noise of three months duration. There were no complaints of instability, swelling or pain. Physical examination showed anterior laxity of the knee. There was no recent history of trauma. The patient is known with a congenital shortening of the left leg for which she has already undergone a leg lengthening procedure.
The MRI examination shows multiple anatomic anomalies. The most notable is the absence of the anterior cruciate ligament (Fig. ). The posterior cruciate ligament is present but appears hypoplastic (Fig. ). The lateral intercondylar spine is absent and the lateral meniscus is hypoplastic (Fig. ). There is severe trochlear dysplasia due to hypoplasia of the lateral femoral condyle and medial patellar facet hypoplasia (Fig. ). Sequellae of earlier leg lengthening procedure can be seen: the left fibula is absent and metallic artefacts are present in the tibia.
Up to this date, the patient was treated conservatively.


A 37-year-old male patient suffered from a sudden swelling in the submandibular region of the right side of the neck. The swelling started initially small and had gradually increased in size to reach 3–4 cm in 1 week, accompanied by pain and local fever. The patient’s history was unremarkable. On extraoral examination, a single, localized, well-defined, ovoid swelling was present in the right submandibular region. On palpation, the swelling was tender, mobile, soft in consistency, compressible but not reducible. Intraoral examination showed no abnormalities. The patient was treated with an antibiotic regimen for 10 days without any significant improvement. All serological parameters were within normal limits, and testing of HBs-Ag, HCV-Ab and HIV-Ag/Ab was negative. Ultrasonography and MRI imaging of the head and neck revealed a well-defined cystic lesion with sharp regular borders measuring 39.8 mm × 19.7 mm within the right submandibular gland (Fig. ). The cyst was then enucleated under general anesthesia. Diagnosis decision was determined on histopathological observations as an inflammatory cyst in the submandibular gland. The patient was reviewed after 6 months with no evidence of recurrence as confirmed by ultrasound imaging.
To examine the possible involvement of IL-34 in the inflammatory response observed in this case, 5-μm thickness sections were prepared from FFBE tissue samples obtained from five different regions of the surgically resected inflammatory cyst in addition to one sample from the adjacent swollen lymph nodes (Fig. ). The expression of IL-34 was examined in these sections as compared to normal human salivary gland tissues (OriGene, Catalog No: CS811918, Case ID: CU0000012638, Sample ID: PA0000964A). Immunohistochemistry staining was performed using a specific antibody against IL-34 (EMD Millipore, Catalog No: MABT493, 1:200 dilution, 4 °C overnight) followed by secondary antibody reaction (ImmPRESS UNIVERSAL REAGENT, Anti-Mouse/Rabbit IgG PEROXIDASE Vector, Catalog No: MP-7500, 30 min at room temperature). Peroxidase/DAB was added, and the sections were counterstained with hematoxylin.
By microscopic observation, normal salivary gland tissues showed typical histology, composing of serous acini mixed with adipocytes and ducts lined by cuboidal epithelial cells (Fig. ). IL-34 expression was undetectable in serous acini or endothelium, but can be observed at very weak levels in the epithelium of the ductal system (Fig. ). As expected, IL-34 showed enhanced expression levels in tissues of the submandibular gland surrounding the inflammatory cyst (Fig. ). In particular, IL-34 showed remarkable enhancement in the cuboidal epithelial cells of the ductal system and interestingly in endothelial cells lining blood vessels within theaffected gland (Fig. ). IL-34 showed very weak staining in some areas within the adjacent swollen lymph nodes (Fig. ). The specificity of the anti-IL-34 antibody was confirmed by the specific staining of keratinocytes in normal skin (BioChain, Catalog No: T2234218, Lot. C105169) (Fig. ). Isotype control antibodies showed no staining in all samples used for IHC in this report (data not shown). To further confirm the expression of IL-34 in these samples, total RNAs were collected from formalin-fixed paraffin-embedded (FFPE) samples (NucleoSpin total RNA FFPE XS, Macherey-Nagel, Catalog No: 740969.10) and then reverse-transcribed into cDNA (ReverTraAce qPCR RT Master Mix, Toyobo, Catalog No: F0937K). RT-PCR analysis on these samples showed elevated levels of IL-34 mRNA in addition to several inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNFα) in the inflammatory cyst of the submandibular gland compared to normal salivary gland tissues (Additional file : Figure S1).
Consistent with this inflammatory condition, high expression of IL-34 in the affected gland showed a tendency to be accompanied with high infiltration of lymphocytes, as confirmed in both cases of the epithelium of the ductal system as well as endothelium of blood vessels (Fig. ). Collectively, these results indicate a potential involvement of IL-34 in the inflammatory response observed in this case of the inflamed submandibular gland.


A 56-year-old woman was referred to our hospital for surgical treatment of a T3N0M0 primary adenosquamous carcinoma measuring 35 × 28 mm in the anterior segment (segment 3) of the left upper lobe without mediastinal lymph node swelling in preoperative computed tomography. The ppo VC and ppo FEV1 were 2.68 L and 2.22 L, respectively. The preoperative computed tomography scan revealed that the tumour had invaded the anterior mediastinal fat tissue and phrenic nerve (Fig. , ).
The patient was placed in a lateral position on the operating table under general anaesthesia with selective lung ventilation. Two thoracoport trocars (15 mm) were placed in the sixth intercostal space (ICS) at the anterior axillary line and in the seventh ICS at the posterior axillary line. An anterolateral mini-thoracotomy (35 mm) was performed in the fourth ICS for left upper lobectomy (Fig. ). We resected the phrenic nerve and pericardial fat with an optimal surgical margin and then performed left upper lobectomy and lymph node dissection. Thoracoscopic diaphragmatic plication was performed with 3–0 Prolene sutures running from the dorsolateral to ventromedial diaphragm in order to oversew the diaphragmatic tendon pars and imbricate the muscle part (Fig. ). Dacron pledgets were only used for the first suture and the suture was retracted to the cranial side during needle stitch (Fig. ). The thoracoscope was placed through the thoracoport trocar in the seventh ICS at the posterior axillary line and the plication was performed through the thoracoport trocar in the sixth ICS at the anterior axillary line with an endoscopic needle holder.
The pathological diagnosis was a T3N2M0 primary adenosquamous carcinoma invading the phrenic nerve with negative surgical margins. The patient’s postoperative course was favourable without any complications. No clinical symptoms were observed during the follow-up. Pulmonary function testing performed 1 year after the surgery revealed VC and FEV1 values of 2.36 L and 2.08 L, respectively. The representative chest radiographs of the left hemidiaphragm showed a normal position preoperatively and only mild elevation postoperatively (Fig. , ).


A 9-month-old boy presented to Department of Otolaryngology for an hour of crying associated with having congee. He was suspected of foreign body aspiration. However, there were no suggestive symptoms, such as dyspnea, stridor, croupy cough, hoarseness, or vomiting. In physical examination, no foreign body was found in the oropharynx. Differences in the intensity, phase, and quality of bilateral breath sounds were uncertain for disturbance of baby crying. Therefore, cervicothoracic computed tomography (CT) scan with virtual endoscopy was taken for excluding foreign bodies of the pharynx, larynx, trachea, bronchi, and esophagus. However, no abnormality was revealed in the CT scan, as shown in Fig. . Then, flexible laryngoscopy was applied for viewing the hypopharynx and larynx. A transparency film, exhibited in Fig. , was visualized on the posterior hypopharyngeal wall, as shown in Fig. . The removal of the foreign body was proceeded immediately. The tongue was depressed for better exposure of the foreign body. Under direct visualization it was removed with forceps.


We report a case of a 18-year-old female patient with previous history of recurrent myopericarditis in 2015 and 2016. In both episodes, troponin I was elevated (maximum value 3.1 ng/mL) and slowly declined. In the last episode she took ibuprofen 600 mg every 8h for 2 weeks and colchicine 0.5 mg twice a day for 6 months. Physical activity was restricted for 6 months. Transthoracic echocardiography was normal but cardiac Magnetic Resonance Imaging (MRI) performed latter demonstrated residual fibrosis in the lateral wall of left ventricle.
The patient remained asymptomatic until June 2017 when she complained of palpitations and mild chest pain. Physical examination, Electrocardiogram (ECG) and transthoracic echocardiography were normal but troponin I was positive (1.04 ng/mL; normal range < 0.04 ng/mL) so myopericarditis was assumed and the patient was admitted
to the hospital and ibuprofen and colchicines were initiated. The next day and until discharge, troponin I remained negative and the patient was free from symptoms. Serology for virus, interferon gamma release assay and clinical or laboratory tests for autoimmune diseases were all negative. The possibility of a false positive test on admission was thought due to the immediate fall in troponin level. However, owing to the relief of symptoms with medication, myopericarditis could not be excluded and the patient was discharged on ibuprofen and colchicine at the same dose as before.
Three weeks later she returned to the hospital complaining of similar symptoms. Once again, initial measurement of troponin I was positive (1.31 ng/mL) and incessant myopericarditis was assumed. Physical exam remained unremarkable as well as the ECG and transthoracic echocardiography. During hospitalization, measurements of troponin I remained always negative. She had a cardiac MRI once again but no signals of active myocarditis were detected and residual fibrosis remained as previously described (Fig. ). Once more, a false positive result was a possibility since the first measurements were performed by the emergency laboratory (Beckman Coulter Access AccuTnI+3®) and the next ones by the routine laboratory (Abbott Architect STAT high sensitive TnI®). To rule out a false positive result in the first measurement, performed by emergency laboratory, two samples of blood were collected at the same time and sent to both laboratories. The result was positive in the emergency laboratory (1.03 ng/mL) and negative in the routine laboratory (0.00 ng/mL). Although alkaline phosphatase activity was within the normal range (58 U/L; normal range 40-150 U/L), alkaline phosphatase interference was proved in the Beckman Coulter central laboratory. To demonstrate that, beta human chorionic gonadotropin (βhCG) was measured using the Beckman Coulter Dxl 800 Total β-hCG® (Marseilles, France) assay [] (which is also an alkaline phosphatase dependent immunoassay) and the βhCG was 1.1 IU/L (age-specific reference interval 0-0.6 IU/L []) while using other assay [Siemen´s Vista hCG (Erlanger, Germany)] was 0 IU/L.
Retrospectively, we confirmed that in the first two admissions, troponin I was elevated in both laboratories (and not substantially higher in one assay relatively to the other) so myopericarditis indeed existed. In order to avoid future hospital admissions, information regarding alkaline phosphatase interference with troponin I and other assays was provided to the patient and added to the patient´s files.


A 42-year-old woman with history of hypertension and diabetes mellitus presented to the outpatient clinic with abdominal pain and diarrhea for two weeks. The patient was recently treated with clindamycin for sinusitis. On examination, the patient appeared comfortable, afebrile, and had normal vital signs. There was mild tenderness reported on abdominal palpation, and the remainder of the physical examination was unremarkable. Clostridium difficile infection was confirmed by a positive stool toxin B PCR, and the patient was started on treatment with metronidazole. Due to complaints of nausea on day three of metronidazole use, the treatment was changed to oral vancomycin at 125 mg every 6 hours. At the time of initiation of therapy, the patient had creatinine of 0.6 mg/dL. After the third day of oral vancomycin, the patient reported new symptoms of lightheadedness, sensations of “buzzing and whistling” in both ears, as well as decreased perception of hearing described as “clogged ears.” The patient presented to the emergency department (ED) due to worsening of these symptoms, and the vancomycin dose was reduced to 125 mg every 8 hours. However, the reported symptoms persisted, and on day 5 of therapy, vancomycin was discontinued in the outpatient clinic. A random vancomycin level obtained 24 hours after the last dose of vancomycin, resulted as 2 mcg/mL. The patient's symptoms were also reported to be resolved within 24 hours after discontinuation of therapy. The temporal association of the patient's symptoms and improvement with cessation of therapy along with a detectable vancomycin level indicates systemic absorption of oral vancomycin with associated ototoxicity.


A 42-year-old male with a history of schizophrenia, hypertension, and bipolar disorder was brought to the hospital secondary to an episode of generalized body shaking and urinary incontinence. Vital signs were stable (temperature 95.8 F, heart rate 98, blood pressure 150/87 mmHg, respiratory rate 16, and oxygen saturation 97% on room air). The physical examination, except the neurological exam, was unremarkable. The patient was extremely lethargic and was alert only to place. He followed basic commands and did not have any significant cranial nerve, motor, or sensory deficits. Blood work was significant for sodium of 106 mEq/L with serum osmolality of 226 U/L and creatine phosphokinase (CPK) of 835 U/L. The sodium was corrected cautiously with a rate of 8-10 mEq/L/24 hours with intravenous normal saline, desmopressin, and fluid restriction (1200ml/24 hours). The patient received two 500 mg doses of levetiracetam. He was continued on intravenous levetiracetam 750 mg every 12 hours. His home medications, including benztropine, risperidone, and trazodone, were initiated. On the third day of admission, the patient`s CPK levels were elevated to more than 30,000 U/L. His creatinine increased from 1.01 to 1.51 mg/dl. Urine myoglobin was also elevated. He was diagnosed to have an acute kidney injury and rhabdomyolysis. Levetiracetam was immediately discontinued, as it was considered to be the possible etiology. The patient was treated with aggressive intravenous fluid hydration (normal saline) for rhabdomyolysis and for the improvement of renal function. A gradual improvement of CPK was noted (Figure ) accompanied by an improvement in renal function as well as in the overall clinical condition of the patient.


A 51-year-old male was referred to our center due to a large perineal mass. The mass was first discovered 30 years ago as a chestnut-sized small movable cystic nodule. Subsequently, he watched himself for a long time because of no unusual changes. The cyst started to grow suddenly 4 months previous to the visit and caused great discomfort in the perineum due to its large size.
On physical examination, an approximately 15-cm cystic mass was observed in the left perineum near the anus. There was no sign of inflammation such as tenderness or redness. Ulceration or discharge was not observed. On a digital rectal examination, there were no specific findings in the anus. A colonoscopy was performed and was unremarkable. Magnetic resonance imaging revealed a 6.7 × 16 cm lobulated mass in the medial aspect of the left perineum with an intermediate signal on T1WI, a high signal on T2WI, and peripheral wall and internal septal enhancement (Fig. ). There was no significantly enlarged inguinal lymph node. Laboratory values were within normal ranges, except for TPLA (+), FTA-ABS IgG (+), and FTA-ABS IgM (−). Preoperative pathologic tests such as fine needle aspiration and core needle biopsy were not performed because the mass was considered as an epidermal cystic mass.
The patient underwent excision of the mass with a negative margin. On exploration, a cystic mass with sebum and keratin was identified in the left perineum (Fig. ). It had a clear margin without invasion of anal sphincter and urologic tissues. Because the preoperative diagnosis was a cystic mass such as an epidermal inclusion cyst made by the MR pelvis, the surgery was performed with minimal gross margin. The skin was preserved as much as possible and closed easily without any reconstruction. Histopathological analysis showed the cyst had a thin wall composed of benign squamous epithelium. Some sections of the wall were thick, indicating a microinvasive squamous cell carcinoma (pTisN0M0, pStage0) (Fig. ).
The patient was discharged 2 days after the surgery without a significant postoperative complication. We performed regular follow-up examinations with CT every 6 months, and he showed no evidence of recurrence at 3 years postoperatively.


A 56-year-old male patient, diagnosed as pancreatic adenocarcinoma in March 2014, associated with multinodular hepatic metastasis. He initiated on chemotherapy with FOLFIRINOX for four months (discontinued due to systemic toxicity), changed to chemotherapy with gemcitabine, for 4 more months. He presented partial response of the pancreatic tumor, progression of hepatic lesions, and worsening of tumor markers (CA19.9 from 2,100 to 18,000U/mL).
Abdominal MRI after second-line systemic chemotherapy showed growth of secondary hepatic lesions in segments II, IVa ( A), VII ( B) and VI ( C), despite the chemotherapeutic management. In an Oncology multidisciplinary meeting, it was decided to perform SIRT.
Three months after SIRT, there was virtually complete necrosis of the lesions observed in the previous MRI ( D to F). Moreover, there were necrotic areas not showing the previous lesions ( D to E). These findings may correspond to necrosis of recent secondary lesions or from the hepatic parenchyma. A wedge-shaped hyperenhancement area stands out around the lesion in segment VII ( E).


A 66-year-old female patient, diagnosed as multiple hepatic metastases of an adenocarcinoma of unknown primary site, according to percutaneous hepatic biopsy. Past history of breast cancer appropriately treated six years ago.
An abdominal MRI showed a bulky hepatic tumor occupying preferably the right hepatic lobe (white line), not involving the portal vein, but it was unresectable ( A). There was diffuse heterogeneity of the coalescent lesions, with central areas suggesting necrosis ( A). Despite the bulky tumor mass, it did not affect over 60% of total hepatic volume, thus allowing performance of SIRT.
Magnetic resonance imaging was performed after 60 days and revealed extensive necrotic areas of infiltrating lesions in the right hepatic lobe, besides complete necrosis of the lesion in the gallbladder bed ( B and E).


A 57-year-old male patient was diagnosed, in 2012, as urothelial cell carcinoma in the left kidney, with lymph node involvement, after presenting macroscopic hematuria. He was submitted to nephroureterectomy followed by systemic chemotherapy with MVAC protocol (methotrexate, vinblastine, doxorubicin and cisplatin) during 6 months. He remained with no evidence of the disease for 22 months.
In March 2015, the MRI showed a single liver metastasis. Stereotactic body radiotherapy (SBRT) was performed, and he underwent four chemotherapy cycles of gemcitabine and carboplatin, remaining with no evidence of disease for 6 months. In December 2015, in a control MRI, multinodular liver metastases were observed ( A), besides involvement of retroperitoneal lymph nodes. In a multidisciplinary Oncology meeting, it was decided to use the MVAC protocol and perform SIRT for the hepatic disease.
Two months after SIRT, the MRI showed larger tumor lesions and exuberant necrotic areas ( B). The magnetic resonance images in diffusion sequence are excellent to assess tumor viability (displaying restriction to pretreatment diffusion “viable tumor”- ( C). In this case, diffusion restriction was absent (absence of tumor) in the post-treatment with SIRT ( D).


A 61-year-old woman presented in September 2014 for workup of a 4-month history of progressive right facial palsy, associated with progressively worsening right facial pain. She reported a history of pleomorphic adenoma, first resected in 1973 with 2 recurrences and excisions in 1993 and 2003.
On physical examination, there was a 2 × 2 cm hard, immobile, right sided preauricular mass, associated with multiple palpable level II lymph nodes. Cranial nerves (CN) were intact bilaterally except for complete right CN VII palsy.
Neck MRI revealed a multiloculated cystic lesion involving the superficial and deep lobes of the right parotid gland, and extending posteriorly to the retromandibular vein measuring 3.5 cm. There were six satellite nodules superficial to the right sternocleidomastoid muscle (SCM), highly suspicious for seeding of pleomorphic adenoma, the largest measuring 6 cm. Subsequent fine needle aspirate (FNA) showed pleomorphic adenoma. The patient underwent right parotidectomy, resection of the satellite nodules, and right level II lymph node dissection.
Pathology revealed carcinoma ex-pleomorphic adenoma, with positive cytokeratin (CK) 7 and negative CK5/6, CK20, P63, and thyroid transciption factor 1 (TTF-1). Two out of the six dissected lymph nodes were positive for carcinoma with no extra-capsular extension. However, there was perineural invasion as well as involvement of the SCM (Figure ).
The patient then underwent right radical parotidectomy with modified radical neck dissection, including levels IA, IB, IIA, IIB, III, IV, and VA, as well as right lateral temporal bone resection. Pathology also revealed carcinoma ex-pleomorphic adenoma involving fibroelastic tissue and skeletal muscles with positive margins. Three out of 13 lymph nodes were involved by carcinoma. There was also vascular invasion with tumor involving both the jugular vein and the internal carotid artery.
Postoperative course was smooth except for a minor post-operative infection treated with intravenous antibiotics. The patient then received adjuvant radiation therapy, to a total dose of 66 Gray (Gy) in 33 fractions using Intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). Radiotherapy course was completed on December 2014.
The patient was then followed up with routine imaging. In August 2016, Brain MRI showed evidence of more than thirty small lesions suggestive of brain metastases. Positron emission tomography (PET) scan showed no evidence of systemic disease.
The patient received 30 Gy in 12 fractions to the whole brain, limiting the dose to the previously irradiated region to 20 Gy, using IMRT, completed in August 2016. Follow up Brain MRI 2 months after radiation therapy showed resolution of the majority of the brain metastatic lesions with only few remaining visible lesions. Follow up Brain MRI 10 weeks later showed progression of the metastatic brain disease with at least 10 visible lesions. PET scan showed evidence of a metastatic liver lesion.
The patient was referred to medical oncology for consideration of systemic treatment. HER-2 staining was performed on the previous surgical specimen and showed overexpression of HER-2 (Figure ). She received four cycles of Trastuzumab Emtansine (TDM1). Follow up PET scan four months later, showed resolution of the liver metastatic lesion (Figure ). MRI brain revealed a significant decrease in the number and size of the metastatic enhancing brain lesions, in keeping with a good response to treatment (Figure ).


A 19-year old male presented to the outpatient department (OPD) with history of sustaining injury to right pinna from a road traffic accident two weeks back. The patient sought treatment in a hospital where primary suturing was done but he developed wound site infection with foul smelling discharge and subsequently presented to us. Examination revealed partial avulsion of right pinna and separation of helix from post auricular skin with intervening sloughed out raw area (). Patient was admitted and started on intravenous antibiotics and underwent a primary debridement and sloughectomy. Infection was progressively controlled with antibiotics and the raw area granulated ().
Due to recurrent risk of failure of sutures and for the benefit of cosmesis, it was planned to provide local flap cover for the raw area with Limberg transposition flap. The recipient area was prepared into a rhomboid as shown in ( and ) and the donor flap marked in the post auricular region as per measurements of the recipient area. Skin flap raised from the post auricular region was transposed to the recipient area and the donor flap sutured to complete the Limberg transposition flap (). Paraffin dressing was applied. There was excellent wound healing as well as cosmesis since the scar was hidden in the post auricular region ().


A 68-year-old male was diagnosed with severe HEMA in early childhood, with less than 0.001% factor VIII activity. The brother of the proband also suffered from severe HEMA, thus the mother must have been carrier of the causative mutation. The children of the proband were male, and consequently, in this part of the family the mutation has not been passed on. Due to the distant past of the diagnosis, no genetic tests had been performed to identify the causative mutation. Around 30% of patients with severe HEMA develop inhibitors during their treatment with factor VIII, especially patients with large deletions and intron inversions. Thus, genetic factors can influence inhibitor development, and different treatment approaches are chosen according to risk of inhibitor development []. However, the proband never developed factor VIII inhibitors, possibly suggesting a smaller and less frequent mutation in F8 than the large intron inversion. Following blood transfusion, the proband was tested positive for HIV-1 and hepatitis C virus in the late 1980s and early 1990s, respectively. The patient was cured for his Hepatitis C infection, but never received any treatment for his HIV-1 infection, since he remained with normal CD4 T cell count over time and was considered an HIV long-term non-progressor (LTNP).
To identify the HEMA causative mutation (as well as possible mutations explanatory for his HIV LTNP phenotype), a blood sample was drawn in EDTA tubes (FLUKA), and peripheral blood mononuclear cells (PBMCs) were isolated over ficoll gradient (GE-healthcare). Integrating HIV DNA in CD4 T cells might result in false positive (somatic mosaic) mutations, or disturb the quality of sequencing. Therefore, CD4 T cells were depleted by magnetic purification (miltenyi biotec). DNA from non-CD4 T cells was purified using allprep DNA/RNA mini kit (Qiagen). Whole exome sequencing (WES) was performed employing Kapa HTP Library preparation and Nimblegen SeqCap EZ MedExome Plus kit and analysed using Nextseq v2 chemistry (2 × 150 bp). SNPs were called relative to hg19. Variant call files (VCF) were uploaded to Ingenuity Variant Analysis (IVA, Qiagen) and variants were compared to population frequencies of variants in the Allele Frequency Community (AFC) database and to frequencies in the 1000 Geneomes project. One hundred thirty thousand six hundred eighty-seven variants were identified in 16,957 genes in the patient, of which seven were located in the F8 gene. Two variants did not pass quality control, thus five variants could be possibly causative (see Table ). Four of the remaining variants had an allele frequency much higher than the disease frequency and were therefore judged as being irrelevant. Therefore, one variant (c.5411_5412delTCT, p.F1804del) remained a potential cause of disease (Fig. ). The mutation was verified in the raw BAM file (Additional file : Figure S1). Ingenuity did not provide any dbSNP ID or frequency for this variant, which is thus denoted as novel. Moreover, the variant was not reported in Coagulation Factor Variant Databases EAHAD.CFDB (), which provides all 5418 known transcript variants in the F8 gene, confirming that the c.5411_5413delTCT, p.F1804del must indeed be novel.


A 34 year old male patient, a worker in the salt mines, presented to us complaining of diminished vision in both eyes since the past 10 years. He also complained of diminished night vision which was stationary and non-progressive. His vital parameters and general physical examination was noted to be within normal limits.
Ocular examination revealed a visual acuity of 6/36 (OD) and FCCF (OS). The pupillary reactions were sluggish in both eyes. The remainder of the anterior segment examination was noted to be normal. Fundus examination (Fig. a, b) showed presence of widespread outer retinal atrophy with visible choroidal vessels and peripheral sub-retinal scarring. The left eye shows evidence of foveal atrophy. A small peripheral rim of normal retina, around 1 disc diameter in size, was noted on indirect ophthalmoscopy.
We initially considered a diagnosis of choroideremia, retinitis pigmentosa and scarred posterior uveitis. There was no family history of nyctalopia and an evaluation of his siblings revealed a normal retina. The blood-work on uveitis also came out to be negative.
We once again reviewed the past medical history and upon detailed inquisition the patient divulged a history of a suicide attempt 10 years ago. He stated that he had consumed the chemical used in the iodination of salt after which he noted the diminished vision in both eyes.
We carried out an OCT evaluation (Fig. c, d) of the patient which showed evidence of outer retinal atrophy with associated sub-foveal scarring which was more pronounced in the left eye. A thinning of the choriocapillaris was evident in the OCT scans along with disruption in the continuity of the retinal pigment epithelium (RPE) in the left eye at the fovea. An examination of the medical records revealed an old fundus fluorescein angiogram, from 10 years ago, which showed prominent areas of choroidal hyperfluoresence due to extensive window defects, indicative of RPE damage (Fig. e, f). An electro-retinogram of the patient noted a flat response in both eyes on scotopic stimulation.


A 50-year-old male patient with a history of nightly lower abdominal pain for three months was transferred to the emergency room at Erlangen University Hospital. First routine examinations revealed that heart, spine, liver and kidney showed no pathological changes. The patient had no diarrhea, no fever and no apparent changes in blood values. Gastroscopy revealed a moderately chronic slightly active H. pylori gastritis as determined by Warthin silver staining and culturing. After collecting a sample by endoscopy, a conventional triple antibiotics therapy for 7 days was prescribed to eradicate gastric H. pylori. As the nightly colics continued for the next three weeks, ultrasound diagnostics was performed revealing a thickened gallbladder wall and signs of inflammation, suspicious for cholecystitis. Two gallstones measuring up to 1.5 cm were detected before removal of the gallbladder by standard laparoscopic surgery. Histopathology suggested a microbial infection as the etiology for the observed pathological changes of the gallbladder.


A 69-year-old male with no significant past medical history presented to the emergency department (ED) after accidental ingestion of hydrogen peroxide. He used concentrated hydrogen peroxide as a home remedy. Intending to drink water, he had accidentally grabbed the incorrect bottle and ingested “multiple gulps.” He soon started to experience multiple symptoms including eructation, flatulence, nausea, non-bloody vomiting and generalized abdominal pain. His computed tomography is shown (). During his stay in the ED he started to complain of headache, blurry vision and was found to have a left homonymous hemianopia, dysmetria and hyperreflexia. He was emergently transferred to a tertiary care hospital for hyperbaric therapy.


A 9-year-old boy presented to a local hospital with vomiting and occasional headache with a blood pressure of 210/170 mm Hg. No obvious diseases were observed on digestive endoscopy and abdominal computed tomography (CT) scan, and no remarkable improvement by medicine treatment. CT scan of the chest revealed a 7 × 5-cm-sized soft tissue mass in the left paraspinal area from T3 to T7 with destruction of the adjacent thoracic vertebra and ribs (Fig. ). Biochemical reports revealed elevated levels of serum norepinephrine, urine norepinephrine, urine dopamine, and serum neuron specific enolase. Serum epinephrine, urine epinephrine, alpha fetoprotein, and carcinoembryonic antigen were within the normal range (Table ). The admitting diagnosis was tumor in the posterior mediastinum: paraganglioma? Before operation, the patient was prepared by orally administering captopril, propranolol hydrochloride, and phenoxybenzamine by mouth. The patient's blood pressure remained stable at approximately 110/80 mm Hg. In addition, body fluid volume was also prepared by vein and mouth in 3 days before surgery.
Thoracotomy was performed through the left fifth intercostal space. Intraoperatively, several membranous and fascicular adhesions existed in the thoracic cavity. The irregular ovoid mass measured 8 × 7 × 5 cm. The tumor originated from the nerve root and adhered to the surrounding tissue. It invaded the spine and chest wall. The mass was tough and rich in blood supply. There were intraoperative changes in the patient's blood pressure, which ranged from 85/50 mm Hg to 180/130 mm Hg. During the resection, the surgeon closely communicated with the anesthesiologist to decide the operative process. Histological studies demonstrated that the mass was a tumor (Fig. ). Immunohistochemical (IHC) studies demonstrated that tumor cells stained positive for synaptophysin (syn, +) and chromogranin A (cgA, +). The positive rate of Ki67 (MIB-1) staining was 2% to 5%. The S100 and PCK staining was negative (Fig. ). The immunohistochemical studies suggested that the tumor was a paraganglioma. Postoperatively, the patient's blood pressure was stable and within the normal range. On postoperative day 2, the concentration of serum epinephrine was 236 ng/L and serum norepinephrine was 4686 ng/L. On postoperative day 4, serum norepinephrine (321 ng/L) and epinephrine (76 ng/L) were normal. The patient was discharged on postoperative day 6. After operation, the patient did not exhibit hypertension and his blood pressure was normal without medicine. After 1 year, follow-up chest CT did not reveal tumor recurrence (Fig. ).


A 12.3-year-old male patient was referred to our pediatric endocrinology clinic for evaluation of short stature. He has been using levothyroxine (LT4) for hypothyroidism for more than 2 years. In medical history, he was born at term weighing 3500 g with uneventful gestation and delivery. His parents were first degree cousins. The height of the mother and the father was 165.5 and 172 cm, respectively. He had three sisters and one brother. His brother and one of the elder sisters were healthy and 175 cm and 165 cm tall, respectively. On physical examination, height was 129 cm (SDS: −3.2) and weight was 28 kg (body mass index, BMI: 16.8, −1.0 SDS). Target height was 175.2 cm (SDS: −0.2). Testicular volume was 2 ml bilaterally with a 3 cm penile length. Bone age was 9 years. Laboratory findings revealed that free thyroxine (FT4) is 1.2 ng/dl (N: 0.61–1.57), thyroid stimulating hormone (TSH) is 0.01 μIU/ml (N: 0.37–5), thyroid autoantibodies were negative, prolactin (PRL) is 4.5 ng/ml (N: 2.6–13.1), adrenocorticotropic hormone (ACTH) is 21.3 pg/ml (N: 4.7–48.8), cortisol is 6.8 μg/dl (N: 6.7–22.6), and insulin-like growth factor 1 (IGF-1) is 12.8 ng/ml (N: 85.2–248.8). Thyroid ultrasonography revealed a hypoplasic thyroid gland (1.7 ml) with normal parenchyma. On pituitary magnetic resonance (MRI), partial empty sella was detected with normal bright spot (pituitary height was 2.8 mm). Clonidine and L.DOPA stimulated peak serum growth hormone (GH) levels were 2.1 ng/ml and 1.9 ng/ml, respectively. With these results diagnosis of GH deficiency was confirmed, and recombinant growth hormone (rGH) was initiated. On follow-up, low dose (1 μg) ACTH stimulation test was performed, and adrenal deficiency was confirmed (peak cortisol: 12.1 μg/dl). Then, oral hydrocortisone replacement therapy was initiated (10 mg/m2/day).
At 14.3 years, he was still prepubertal with testicular volume of 3 ml bilaterally. Basal level of testosterone was <0.01 ng/ml. Then, LHRH stimulation test was performed, and central hypogonadism was confirmed (peak luteinizing hormone, LH; 0.62 mIU/ml, and peak follicle stimulating hormone, FSH; 0.85 mIU/ml). Intramuscular depot form of testosterone was initiated, 50 mg/monthly.


A 55-year-old woman reported a 24-hour history of unusual pain in her left carotid area irradiating to the ear. Colour Doppler ultrasound revealed an eccentric hypoechoic thickening (black arrows on Figure ) of the proximal bulbar internal carotid but also partially of the carotid bifurcation itself. A thin hyperechoic atheromatous fibrous plaque was also visible (small white arrows on Figure ) but no significant stenosis was found. Contrast-enhanced ultrasound showed normal capillary distribution of micro bubbles in the hypo echoic thickening, therefore excluding haematoma (Figure , black arrows). The avascular fibrous plaque was well demonstrated (small black arrows). Unenhanced Axial T1-weighted Magnetic Resonance (MR) imaging showed an hypo intense tissue (Figure , black arrows) around the proximal internal carotid. Intense enhancement of this tissue was shown on fat-saturated contrast enhanced T1-weighted images (Figure ). Carotidynia or TIPIC syndrome was diagnosed and the woman was immediately treated with non-steroid anti-inflammatory drugs. Doppler ultrasound performed after 14 days already showed rapid regression of both the symptoms and the perivascular inflammatory sheath (black arrows on Figure ).


Written informed consent for publication was obtained by the patient's parents.
Our patient is an 8-year-old girl, with a positive family history for both skeletal malformations and bipolar disorders (BD). Her pre-perinatal history was uneventful. She was referred to our Unit because of learning difficulties and behavioural problems. The neurological examination did not show focal neurological deficits. Dysmorphic features were evident at the first observation. She showed several facial dimorphisms such as flat face, blepharophimosis, hypertelorism, broad nasal bridge, and high palate. Bones and joints defects were also evident: pectum excavatum, single transverse palmar crease, brachydactyly, flat foot, and stature below 25th percentile (). Because of these features, she previously underwent genetic consultation and performed array-CGH analysis revealing a chromosomic 8q22.1-q22.3 duplication (hg19/96.846.254-101.630.576x3, 101.726.279x2) encompassing the GDF6 and SDC2 genes, inherited from her father. Thus, our 8-year-old girl presented with clinical and genetic features of Leri's pleonosteosis, within a larger microduplication involving different genes not strictly related to our patient phenotype. In particular, the hypothesis of autosomal recessive optic atrophy (OPA6) was excluded by a general ophthalmologic examination and a fundus examination, since the contiguous region 8q21.13-q22.1 is responsible for recessive optic atrophy [].
She also met the DSM-5 criteria for attention-deficit/hyperactivity disorder (ADHD), specific learning disorder, speech sound disorder, and developmental coordination disorder. In particular, she showed a highly pressured pattern of speech, difficulty in sustaining attention, high levels of activity, and low frustration tolerance. Furthermore, she presented a pattern of bipolar-like phenomena that did not meet the criteria for bipolar I, bipolar II, or cyclothymic disorder. Nevertheless, according to DSM-5 category, she met the criteria for the diagnosis of “other specified bipolar and related disorder” owing to the occurrence of hypomania episode without prior major depressive episode or a manic episode.
The clinical features are shared with both her father and her grandfather that present an overlapping duplication in the 8q22.1-q22.3 region. They show facial dimorphism (flat face, blepharophimosis, hypertelorism, and broad nasal bridge) and brachydactyly and are affected, respectively, by cyclothymic disorder and bipolar II disorder. Also her grandfather's brother received a diagnosis of bipolar II disorder. Unfortunately, he has never performed an array-CGH analysis, but he shows skeletal malformations consistent with Leri's disorder. Along paternal line of our patient, more members are affected by mood disorders associated with skeletal deformations. Unfortunately, none of them agreed to perform the array-CGH analysis, thus the information is incomplete to build a family tree chart. Nevertheless, the chromosome 8q22.1 microduplications were documented in our patient and his father and grandfather.
Our 8-year-old girl's developmental milestones had been mildly delayed. In particular, she presented a delayed achievement of the expressive language. Thus she started a speech-language therapy when she was 4-year-old and continued it for two years. During infancy, she also presented a divergent strabismus surgically treated at the age of 3 years. She also had genu recurvatum and hip developmental dysplasia (type-II Graf) within the first year of life. Our first neurological examination failed to detect major focal signs, but gross and fine coordination impairments with orofacial dyspraxia and speech phonological deficits were observed.
The behavioural observation revealed high levels of impulsivity and a persistently elated mood with increased activity and energy for most of the day. She often displayed restlessness, hyperactivity, and difficulty remaining focused. She also was more talkative than usual and prone to engage conversations with strangers in public, with an indiscriminately friendly approach and a high level of enthusiasm. On the whole, her social behaviour towards adults was often inappropriate. Furthermore, the conversation content appeared inappropriate to the contest with flight of ideas and abrupt shifts from one topic to another. She also showed amusing irrelevancies and theatrical mannerisms and an inflated self-esteem with uncritical self-confidence. Moreover, rapid shifts in mood over brief periods of time might occur. During these episodes, her mood became irritable and she presented decreased need for sleep, diminished ability to concentrate, inconclusiveness, and angry bursts when her wishes were denied.
The neuropsychological assessment included the cognitive profile (WISC IV) [], visual perception and motor coordination (VMI) [], executive functions (TOL) [], and verbal and spatial memory (Corsi test) []. The IQ score was in the low average (total IQ score 88), with the lowest score in nonverbal and fluid reasoning (perceptual reasoning index = 80). A moderate impairment was revealed in visuospatial short-term working memory (Corsi backward span = 2; −1.89 SD) and in backward verbal span (digit backward span = 2; −1.29 SD). Planning ability was largely below the average (rule violations = T > 100, >−2 SD; number of additional moves = T > 100, >−2 SD, TOL), suggesting a poor mental planning and problem-solving skills. She also showed deficits in visual perception and motor coordination skills at the visual-motor integration test (VMI Beery, 1997; standard score = 78; 7th percentile). The reading and writing tests scored below the average (oral reading speed of a text: 0.88 syllables/seconds/−2 DS; number of errors = 14/5° percentile; writing errors: −2 DS). She lacked knowledge of spelling rules that made her enable to read and write complex words. In general, she showed difficulties in managing the aspect of phonological processing which underpins the acquisition of literacy. Working out meaning from a whole sentence was another of her weaknesses due to the working memory deficit. Instead, when dealing with words in isolation, she had less difficulty in comprehension. She also showed very low concentration and attention abilities. During the assessment, she had to be constantly refocused and prompted to continue. All in all, our patient's neurodevelopment and psychiatric symptoms caused a marked impairment, especially in social relationship and in academic performance.


We present a clinical case of a 31-year-old man diagnosed with HIV-1 infection, with CD4 T cell count of 35 cells/mm3 (4%) and HIV RNA 305349 copies/mL (log10 5.48) having initiated ART with abacavir/lamivudine and nevirapine. Around two weeks after starting ART, the patient is admitted due to a sudden cognitive impairment (anhedonia and memory loss) with progression to gait change and imbalance. The cranial computerized tomography (CT) scan showed no lesions but the cranial MRI revealed ventriculoencephalitis ().
The cerebrospinal fluid (CSF) had 38 nucleated cells/mm3, 175 mg/dL proteins and 37 mg/dL glucose (glycaemia 82 mg/dL). The CSF CMV and EBV viral load were 189000 (log10 5.28) and 799 (log10 2.90) copies/mL with negative CSF neurotropic microorganism serologies and molecular identification (HSV 1/2, VZV, Cryptococcus, Brucella, Treponema pallidum, Borrelia burgdorferi, JC virus, Mycobacterium tuberculosis, and Toxoplasma gondii). The final considered diagnostic was mainly CMV-related ventriculoencephalitis and ganciclovir was started.
Nevertheless, the patient started left conjugate horizontal gaze palsy with abducting horizontal saccadic (or jerk-type) nystagmus of the right eye as well as a slight anisocoria with left eye miosis. These changes were enclosed in the one-and-a-half syndrome and left-sided Horner's syndrome. The patient also presented a grade II-III paresis of the right lower limb. The cranial CT scan (performed fifteen days later) revealed a dubious right linear protuberancial hypodensity without signs of intracranial hypertension.
Cranial MRI was repeated one month later revealing improvement of the ventriculitis signs but a larger hippocampus and left mesial temporal region involvement with a discrete increase of the lateral ventricles dimensions.
Due to these clinical and imagiological changes and because we could not exclude tuberculosis infection, classic first-line tuberculostatic therapy was empirically started (stopped after excluding this infection) and foscarnet was added to ganciclovir (until a negative CMV viral load was achieved). At this point, the hypotheses of limbic encephalitis, epileptic activity or paraneoplastic encephalitis could not be excluded. The lumbar puncture was repeated and CSF antineuronal antibodies, HHV-8, and other neurotropic microorganisms were negative.
The electroencephalogram (EEG) showed frontal and frontotemporal bilateral activity with occasional periodic discharges, independent of nonabrupt three-phase bifrontal lesions. Anticonvulsant therapy with levetiracetam and topiramate was started. One month later, the cranial MRI was repeated and a new frontal lesion was detected. The body CT scan was normal. The imagiological reevaluation showed a slight improvement of the frontal lesion with new cerebellum lesions. The suspicion of lymphoproliferative disease was meaningful. Cranial MRI with diffusion and perfusion study with spectroscopy was performed and revealed very suggestive images of CNS lymphoma (). For definitive diagnosis, a stereotactic brain biopsy was done. The histological study revealed a polymorphic cellular infiltrate with histiocytes, CD3+ T-lymphocytes, and CD 20+ B-lymphocytes (mixture of numerous small cells and large activated cells with positive hybridization results for EBV-encoded RNA (EBER)). The histology was suggestive of polymorphic lymphoproliferative EBV-positive disease. The molecular studies were not done because the sample was insufficient to perform the clonality analysis (CSF EBV viral load was 12405 copies/mL; CSF HIV and CMV viral load were both undetectable).
At this point, chemotherapy with rituximab was started and radiotherapy was scheduled. Nevertheless, the patient developed a sudden neurological worsening with a generalized tonic-clonic seizure, refractory to the instituted measures, culminating in death.


A 28-year-old male was transferred to our hospital in November 2006 because of a sudden onset of cramping and abdominal pain and intermittent melena for 4 days. Initially, he exhibited symptoms including generalized weakness, dizziness, and massive bloody stool passage. There was no significant past medical history of recent infection, inflammatory bowel disease, bleeding disorders, changes in bowel habits, significant weight loss, or tuberous sclerosis complex. The patient had no previous surgeries, and the family history was unremarkable. The patient's height was 180.2 cm, weight was 78.5 kg, blood pressure was 74/39 mm Hg, pulse rate was 122 beats/min, and temperature was 36.4°C. The physical examination revealed moderate distention and tenderness in the left lower quadrant with associated defense. On digital rectal examination, there was some gross blood mixed with soft stool and an empty ampulla. Laboratory data showed a white blood cell count of 17,120/mm3, hemoglobin level of 7.4 g/dL, hematocrit of 23.9%, and platelet count of 162,000/mm3. Other biochemical tests were normal. The serum carcinoembryonic antigen level was normal.
The gastroscopic evaluation was normal. The full colonoscopy revealed a greater than 4.0 cm in diameter, large ulceration with an easy bleeding mass of the rectum lying beneath the mucosa but protruding into the lumen 15 cm from the anal verge (Fig. ). This tumor could not be classified by biopsy. However, on the basis of the immunohistopathological features, carcinoma and malignant lymphoma could be excluded. An abdominal enhanced CT scan revealed a heterogeneous mass lesion of approximately 8.9 x 7.2 cm in the pelvic floor at approximately the level of the rectum (Fig. ). A technetium-99m red blood cell scan showed no significant findings. Repeated attempts at endoscopic revaluation resulted in profuse bleeding requiring blood transfusions. A diagnostic biopsy failed before the surgical treatment due to bleeding from a light touch of the mass lesion
Given the difficulty of obtaining a diagnostic specimen, surgical resection and lower anterior resection were performed. On gross examination, the resected specimen was an 8.8 x 5.5 x 4.5 cm, tan, gray-white, soft, and well-circumscribed transmural mass of the rectum, mainly involving the muscularis propria and protruding into the tunica adventitia. The mucosa and submucosa were intact (Fig. ). The tumor protruded into the lumen, and the overlying mucosa showed ulceration. The tumor had a dark, red-grey, solid parenchyma with irregular cystic spaces with colorless serous liquid (Fig. ). The cut surface showed a yellowish-tan to gray-red solid parenchyma with focal irregular cystic spaces containing colorless serous fluid (Fig. ). All surgical margins were macroscopically free of tumor. No separate polyps were identified. Microscopically, the foci of hemorrhage and necrosis were present. The tumor extended through the muscularis propria into the subserosa tissue with lymphatic invasion. The colon mucosal tissue was composed of sheets with atypical glands with spindle-to-epithelioid cells and nuclear abnormalities in a tubular arrangement (Fig. ). Perivascular hyalinization was noted (Fig. ). Most tumor nuclei showed clear to granular, light, eosinophilic cytoplasm, and round to oval nuclei with distant small nucleoli pleomorphism (Fig. ). Less than 50% of the tumor area was necrotic. The mitotic rate was low. One of 27 accompanying serosal lymph nodes contained metastatic tumors that distended the subcapsular sinus. All of the surgical margins were free of tumor. Immunohistochemically, the tumor cells were positive for melanoma-associated antigen (HMB-45) (Fig. ) but negative for cytokeratin, c-kit, synaptophysin, S-100, and actin. A diagnosis of metastatic PEComa was made after examination of the resection material.
Unfortunately, the patient did not complete the follow-up in the outpatient department after surgery because he relocated to another city to seek work. At the 49th month (2010) postoperatively, the patient returned to the clinic upon our scheduled request. An abdominal CT scan showed a 0.6 cm hypodense mass over the liver. He refused further evaluation and treatment. In July 2014, during the course of a required physical health check, he received an abdominal CT that showed that the original mass had increased from 0.6 to 1.5 cm and that the number of tumors had increased from 1 to 3 compared with the previous CT image in 2010. We noted that the distant liver metastasis progressed very slowly during the 4 years of follow-up. The liver function and the other serum tumor markers were normal upon examination. In August 2014, he underwent segmental hepatectomy (S3, S4A, S5, and S6) combined with wedge resection. The pathology report of segmental hepatectomy was metastatic PEComa.
This patient underwent 2 different surgical resections at 2 different times. He underwent the lower anterior resection of the PEComa of the rectum in 2006 and received the segmental hepatectomy in 2014. He is currently undergoing regular surveillance and has remained free of disease 28 months after the second operation. At the follow-up examination, the patient felt well, and the general clinical examination, subsequent colonoscopies, and abdominal CT scan once every 3 months revealed no significant findings after second operation in 2014. Since the primary surgery in 2006, there was also no recurrence of the PEComa of the rectum according to the general clinical examination, subsequent colonoscopies, and abdominal CT scan at the 120-month follow-up of the very first instance back in 2006.


A 3-year-old girl was admitted for fever and cough. She was diagnosed as having pleuresia and pleural drainage along with broad spectrum antibiotics was prescribed. Lack of improvement after a few days led to complete the work-up with a CT scan (Fig. a, b). The scan showed a tissular lesion of the left lower pulmonary lobe associated with a tumor of the right kidney. Lung biopsy showed blastema, without being able to distinguish whether its origin was WT or PPB despite multiple analyses by various pathological experts. Following the recommendations of the national panel of expert of both tumors, we decided to treat the patient as a metastatic WT following the International Society of Paediatric Oncology protocol (SIOP WT2001) []. A nephrectomy was thus performed after 6 weeks of chemotherapy (vincristine and actinomycin), with a good response in both sites (Fig. ).
Histologic analysis confirmed the diagnosis of WT with an intermediate risk (epithelial type) which was classified as a stage IV. Lung surgery was scheduled several weeks later. During this period, using high-throughput sequencing of a panel of genes involved in endocrine tumor development, we identified a heterozygous pathogenic variant in exon 23 of the DICER1 gene (LRG_492). This variant c.4407_4410del, p.Ser1470Leufs*19, leading to loss of the RNase III active site, has been previously associated with pleuropulmonary blastoma [].The mutation was confirmed by Sanger sequencing (Fig. ). This led to a high suspicion of associated PPB. Pre-operative workup showed increase in tumor size, and chemotherapy was modified (by adding ifosfamide and doxorubicin) to try to reduce tumor volume and vascularization. After the first course of chemotherapy, the patient developed respiratory distress due to a massive increase in tumor size, leading to mediastinal compression. It was then decided to remove the left lung (Fig. e, f).
A left pleuro-pneumonectomy with intra-pericardic ligature of the vessels and without cardiac assistance was performed. The early postoperative course was uneventful. The pathologist confirmed the diagnosis of type 3 PPB with R0 resection. Postoperative chemotherapy consisted of eight courses (27 weeks) of vincristine, actinomycin, and doxorubicin. After 1-year follow-up, the patient remains asymptomatic and is considered to be in remission.


An 80-year-old man residing in a nursing home, with a past medical history of a prior stroke, hypertension, hyperlipidemia, diabetes mellitus, dementia, and gastrostomy tube placement (inserted endoscopically two years before) due to dysphagia secondary to the stroke, presented to the emergency department (ED) with hematemesis and bleeding around the gastrostomy site. A review of his medication list revealed that he was taking aspirin 81 mg daily but no additional, nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet drugs, or anticoagulants. On physical exam, he appeared exhausted. He was tachycardic (pulse rate 116 BPM), hypotensive (blood pressure 98/65 mm Hg), and febrile (temperature 100.6°F). The abdomen was soft and not distended, with no tenderness and normoactive bowel sounds. There was no guarding or rigidity. A gastrostomy tube was seen, and the scale indicated that the internal bumper had dislodged (Figure ). Dried blood was seen at and around the gastrostomy site. On rectal exam, melena was discovered.
Aggressive intravenous hydration with normal saline was given. Laboratory testing was performed and the complete blood count (CBC) showed hemoglobin of 6.8 g/dL (12.0 - 15.5 g/dL) with an unknown baseline, hematocrit of 21% (34 - 48%), white blood cell count of 12.4 × 109/L (4.0 - 11.0 × 109/L), and platelet count of 382 × 109/L (150 - 450 × 109/L). The comprehensive metabolic panel (CMP) was remarkable for an elevated blood urea nitrogen of 42 mg/dL (7 - 22 mg/dL) and creatinine of 1.2 mg/dL (0.6 - 1.3 mg/dL). The liver function tests were normal. Two units of packed red blood cells were transfused.
Repeat laboratory testing performed the following day showed a hemoglobin of 9.0 g/dL (12.0 - 15.5 g/dL) and a hematocrit of 27% (34%-48%). Esophagogastroduodenoscopy (EGD) was performed and revealed a large gastric ulcer, with signs of recent bleeding, at the site of contact with the internal gastrostomy tube bumper, which had compressed and ulcerated the gastric wall (Figure ). The dislodged gastrostomy tube was removed, and a new balloon gastrostomy tube was inserted, via the gastrostomy, into the stomach. The position of the balloon in the stomach was confirmed by endoscopy. The internal balloon was inflated with 15 mL of water.
Enteral feeding was successfully resumed the following day. Over the next few days, the patient’s clinical condition improved, and he returned to his nursing home.


A 77-year-old man with diabetes mellitus and hypertension presented with right lower quadrant (RLQ) abdominal pain that started a few weeks prior to his presentation. Physical examination revealed a palpable RLQ mass. An abdominal computed tomography (CT) scan revealed a 5.5 cm irregular soft tissue mass abutting the ascending colon medially (Figures , ).
Colonoscopy revealed diverticulosis in the sigmoid and ascending colon. On positron emission tomography (PET) scan, the mass exhibited increased metabolic activity suspicious for biological tumor activity (Figure ).
A CT-guided biopsy revealed inflammatory cells. The patient underwent a diagnostic laparoscopy, and a fresh frozen section was inconclusive for malignancy. This was followed by a robotic-assisted right hemicolectomy en bloc with the mass. Pathology showed diverticulitis with localized suppurative granulomatous inflammation in pericolic fat (Figure ).
The non-caseating granulomas consisted of epithelioid histiocytes with abundant eosinophilic cytoplasm and eccentric nuclei (Figure ). Immunostains were positive for CD68 (Figure ) and vimentin (Figure ) and negative for pancytokeratin (Figure ), eliminating the possibility of a carcinoma or sarcoma.
The patient improved clinically and was successfully discharged after few days of his surgery.


The patient was a 10-year-old right-handed boy. The duration of the illness was 3 years. The first episode occurred at the age of 7 years, without obvious inducement. Symptomatic manifestations included sudden shouting, right-side strabismus, salivation, and generalized tonic-clonic seizures (GTCS), which lasted for about 4–5 min. The second episode occurred 10 days later, with similar symptomatic manifestations. There was no seizure for 1 year after oral oxcarbazepine medication. Seizures then occurred at the age of 8 years, with symptomatic manifestations such as panic, shouting, and tachycardia and lasted about 1–2 min without loss of consciousness. Headache, left eye pain, abdominal pain, and nausea would occasionally appear in the post-ictal period. Gradually, the patient's seizure frequency ranged from once a month to 4 times/day. Oral administration of oxcarbazepine was ineffective. History of perinatal hypoxia, febrile convulsions, brain injury, and family history of epilepsy were negative. Physical examination showed stable vital signs, and the results of neurological examination were normal. Blood routine, biochemical tests, infection immunoassay, blood coagulation tests, and urinalysis were all normal. Electrocardiogram and chest radiography showed normal results.
To evaluate the ictal fear, both video observation and neurologic interview were conducted according to the diagnosis criteria of ictal fear (). First of all, fearful facial expression and screaming had been observed before the clinical seizure (Figure ). The content of screaming includes “Aha! Aha!” or “Mama!” or “Mama! Find the doctor!” Secondly, the patient could remember and describe feelings of fear, without any specific content or scene. Visual aura or other associated aura was denied. The last but not the least, the patient described this fear feeling start abruptly, concomitant with the seizure.
Scalp video EEG (vEEG) were recorded using a Nicolet video-EEG monitoring system (Thermo Nicolet Corporation, USA), digitized at the rate of 1,024 Hz with the international standard 10–10 electrodes montage. The on-line band-pass filter was 1.6–150 Hz. The patient was monitored for a total of 6 days. During the monitoring, oxcarbazepine was gradually reduced and one typical epileptic seizure was captured (Figure ).
Figure shows the vEEG waveforms during the interictal period. Interictal epileptiform discharges (IEDs) could be observed (denoted by red arrows), which were mainly distributed within the left occipital electrodes (P7 and O1). Figure shows the vEEG waveforms before the epileptic seizure. The EEG onset occurred 1.5 s earlier than the ictal fear. Fearful facial expression and screaming could be observed in the video (Figure ).
Brain imaging results showed that while the T2 signals within the left posterior temporal, occipital, and parietal lobes were high, the T2 signals in the left hippocampus was higher (Figure ). Further positron emission tomography/computed tomography (PET-CT) examination showed that low metabolic areas were mainly distributed in the left posterior region (Figure ).
Stereotactic electrodes were intracranially implanted for further epileptic zone evaluation. A robot-assisted stereotactic operation system (ROSA) was used to place 13 electrodes. The sEEG electrodes were manufactured by Huake Hengsheng Medical Technology Co Ltd., Beijing, China. The diameter of a depth electrode was 0.8 mm. The length of each node was 2 mm, which were spaced 1.5-mm apart from each other. The reference electrode was placed on the forehead. On recording days, the impedance of all the recording electrode nodes was kept below 50 kΩ, and the nodes whose impedances were higher than this value were excluded from analyses. Video EEG was monitored for 6 days after implantation, and the oxcarbazepine dosage was gradually reduced during the monitoring; during this period, a total of 4 seizures were captured. Three-dimensional brain images were reconstructed by pre-implantation of T1 images using BrainSuite (Version 18a, ). Pre-implantation PET-CT and post-implantation CT (included electrode localizations) were co-registered to pre-implantation T1 images using BioImage software (). The localization of sEEG electrodes were then presented using the Brainstorm toolbox [(); ] in the MATLAB environment (Figure ).
Figure shows the sEEG results before a representative seizure. A bipolar lead view showed that the EEG onset was 1 s before ictal fear and 12 s before amygdala (A1-A2) and posterior hippocampus (C2-C3) (Figure ). At the moment of the start of EEG, simultaneous direct current (DC) drifts were observed in J5-J6, J6-J7, J8-J9, K5-K6, and K6-K7, with high frequency components in spectra (Figure ). Direct electrical stimulation (frequency = 50 Hz; pulse wide = 0.3 ms; duration = 5 s; intensity = 1–6 mA) confirmed that only stimulation on J8-J9 could evoked a clinical seizure.
According to the sEEG results, the epileptic zone was mainly distributed in the right posterior parietal, posterior temporal, and occipital areas (Figure ), and then propagated to the posterior part of the middle and inferior temporal gyrus, the posterior part of the hippocampus, the anterior part of the lingual gyrus occipital tongue, and the anterior part of the precuneus. Combined with the evidences of brain imaging (T2 flair and PET-CT), the resection range was planned as shown in Figures ,B shows the actual lesion area a year after surgery. The pathological examinations showed focal cortical dysplasia (FCD) type 2A in the right parietal-occipital area.
According to the follow-up, the neuropsychological performance before and after the surgery were all in the normal range (Table ). No seizure occurred after surgery.