We evaluated a 4 years old girl, previously healthy, with no relevant family medical history. She was conducted to our clinic because of a submandibular lymphadenitis. A month before, during a 3 days fever period, a painful submandibular swelling was noted. Neck ultrasound (US) showed a 2-cm diameter lymphadenopathy with a conserved structure. Therapy with ibuprofen was then suggested. Because of symptoms persistence, a control US was repeated after 5 days. The lymph node was enlarged and presented a subverted structure, with hypoechogenic areas and an absent roundness index (Fig. ). Therapy with co-amoxiclav was immediately started at a dosage of 80 mg/kg/day for 6 days. Blood tests showed a slight increase in C-reactive protein values (53 mg/L; normal value <50 mg/L) and erythrocyte sedimentation rate (31 mm/h); serology for Cytomegalovirus confirmed a previous infection, while IgM for Epstein Barr Virus (EBV) were positive. Blood smear was normal. Tuberculin skin test resulted positive (10 mm infiltration diameter). QuantiFERON-TB Gold In-tube test and chest X-ray resulted negative.
Neck US performed after 20 days was unchanged. Therefore the girl was referred to our infectious disease unit for further investigations. At physical examination, a fixed right submandibular lymphadenopathy, with an elastic consistency, painless and with no superficial skin alterations was detected. No other significant clinical features were described. Blood tests showed no alteration in blood count, inflammatory markers, liver function, lactic dehydrogenase, coagulation. Francisella tularensis and Toxoplasma gondii serology were negative. EBV serology showed evidence of a past infection.
In the suspicion of an NTM lymphadenitis, antimicrobial therapy with clarithromycin (15 mg/kg/die), and rifampicin (20 mg/kg per day) was started. A magnetic resonance imaging showed a confluent lymphonodal pack inside the inferior pole of the right parotid gland (4 × 4.2 × 2.9 cm) that was enhanced after contrast medium infusion. The enhancement involved also the whole parotid gland parenchyma and the ipsilateral sternocleidomastoid muscle.
Due to sudden enlargement of swelling, exeresis of the lymph node was performed. Bacterioscopic exam showed a positivity for acid-fast bacilli, and the histological examination evidenced a granulomatous inflammation. Culture from the biopsy grew a M. marseillense strain, identified using a commercial kit (Hain Genotype Mycobacteria CM, Hain Lifescience, Germany) and sequencing the spacer region interposed between 16S and 23S rRNA genes, as described previously []. Because of a slow healing up of the surgical scar, ethambutol (25 mg/kg/die) was added to the previous therapy. Antimicrobial treatment was well tolerated by the patient and no adverse effect were reported. Blood exams and clinical assessment were periodically performed in order to evaluate potential drug-induced toxicity. Therapy was finally stopped 2 months after surgery.
Periodical blood tests and neck US were performed. At 10 months follow up visit, no relapse was found and the surgical scar was completely healed.


A 50-year-old Filipino woman with a past medical history of MCTD, diagnosed 7 years prior, presented to the emergency department with complaints of shortness of breath, chest pain with a “bubble” like sensation, and diaphoresis with minimal exertion. She also had positive Raynaud’s phenomenon. Ten days prior she went to the emergency department for self-limited shortness of breath at which time her creatinine (CRE) was 0.8 mg/dL. Two months prior she was started on hydroxychloroquine 400 mg/day and prednisone 60 mg/day for a MCTD flare that manifested as muscle weakness. Her other home medications were amlodipine 5 mg/day, aspirin 81 mg/day, topical nitroglycerin to fingers 6 times/day as needed, alendronate 70 mg/week, and calcium carbonate/vitamin D3 daily. She has never smoked, never used illicit drugs, and denies consumption of alcoholic beverages.
The patient’s vital signs were unremarkable with a blood pressure reading of 116/80 mm Hg. Physical examination was remarkable for mild distress, a systolic murmur, crackles to mid lung fields, and a blanchable maculopapular rash on the chest.
Complete blood count reveled a leukocyte count of 9.1/mm3 and a platelet count of 205 000/mm3. Hemoglobin was 8.3 g/dL. Biochemical investigations were remarkable for elevated serum urea (53 mg/dL) and CRE (4.3 mg/dL). Liver enzyme tests revealed a total bilirubin of 1.5 mg/dL, an alanine transaminase level of 70 IU/L, and an alkaline phosphatase level of 124 IU/L. Serum lactate dehydrogenase was 343 U/L, and serum haptoglobin was 38 mg/dL (ref 30-200 mg/dL). Urine analysis revealed ++protein, ++white blood cells, 10 to 20 RBC/hpf (red blood cells per high-power filed), and granular casts. Urine microscopy was not done due to suspected diagnosis being MCTD flare. Her spot urine protein to creatinine ratio was 0.8 g/day. Her autoimmune workup was positive for speckled antinuclear antibody (1 in 2560), anti-RNP-topoisomerase I and -Smith antibodies. Complements C3 and C4 were decreased (39 and 7 mg/dL, respectively). Anti–double stranded DNA, -Scl 70, -JO1, -SS-A, -SS-B, and -centromere antibodies were negative. Cytoplasmic-staining (C)-ANCA and perinuclear-staining (P)-ANCA were both negative.
Abdominal ultrasound revealed gallbladder wall thickening. Computed tomography of the chest without contrast showed fibrotic inflammatory changes in the posterior basal segments, bronchial thickening with infiltrates suggestive of bronchopneumonia, an enlarged pulmonary artery, and moderate sized pleural effusions (right greater than left). Echocardiography showed an ejection fraction of 55%, a pulmonary artery pressure of 26 mm Hg, and a moderate sized pericardial effusion.
The patient was diagnosed with a MCTD flare, renal failure, and pneumonia. Hydroxychloroquine was discontinued. She was started on nifedipine, for worsening Raynaud’s phenomenon, methylprednisone 500 mg intravenous daily, vancomycin, and pipercillin/tazobactram. Her CRE continued to deteriorate (5.2 mg/dL), and her blood pressure continued to rise to 150/90 mm Hg. She was sent for a kidney biopsy. On day 4 methylprednisone was discontinued (for concern of precipitating SRC) and captopril (titrated to maximum dose within 72 hours) was started. On day 6 the patient developed oliguria and signs of hypervolemia. Hemodialysis was initiated every other day for a total of 6 sessions. The renal biopsy showed 9 available glomeruli with rare intraglomerular thrombi, moderately thickened vessels without onion skinning proliferation, or mucoid changes in their walls. No hypercellularity, necrosis, or crescent formation was seen. None of the glomeruli were globally sclerotic. One glomerulus had a thrombus within an afferent arteriole at the hilum (). Multiple red cell casts within tubular lumina were noted with mild interstitial fibrosis. The tubules were dilated with flattening of the tubular epithelial cells, suggestive of marked acute tubular injury. Immunofluorescence microscopy revealed no deposition of IgG, IgA, IgM, C3, and C1q. There was no evidence of SRC or other forms of hemolytic-uremic syndrome (HUS)-type thrombotic microangiopathy. The findings of intraglomeruli thrombi were most compatible with thrombotic thrombocytopenia (TTP).
On day 8 the patient became acutely altered. Her complete blood count reveled a platelet count of 80/mm3 and hemoglobin level of 5.8 g/dL. Laboratory data revealed an elevated lactic acid dehydrogenase level of 466 U/L and a decreased haptoglobin level of <10 mg/dL. Complements C3 and C4 were both still decreased (42 and 6 mg/dL, respectively), and serum cardiolipin IgG was positive. A peripheral smear revealed fragmented red blood cells and anisocytosis. She was transfused multiple units of packed red blood cells without improvement. Due to the worsening MAHA along with the aforementioned presentation she was started on plasma exchange (using thawed plasma at 1.0 volume exchanges) for presumed thrombotic thrombocytopenia. On day 9 laboratory values for ADAMT-13 and atypical HUS (aHUS) were drawn and sent out. Methylprednisone 500 mg intravenous daily and mycophenolate at 1000 mg twice daily (chosen over cyclophosphamide due to lack of crescents, pauci-immune glomerulonephritis, and necrotizing inflammation on renal biopsy) were added to further control the MCTD flare. Treatment with eculizumab was considered but the patient refused. Daily pulse dose steroids at 500 mg was restarted with plasma exchange and continued (total of 6 exchanges received) until day 11. There was minimal response of a rise in platelets to plasma exchange with a count of 79/mm3 after her last treatment. Her last hemodialysis received was on day 13 at which time her CRE was 4.8 mg/dL. Over the month of hospitalization her serum CRE and urine output continued to improve and she was discharged with a CRE of 1.7 mg/dL and platelet count of 273/mm3. Her discharge medications were mycophenolate 500 mg twice daily, nifedipine extended release 60 mg/day, and lisinopril 20 mg/day. She was seen in clinic 6 weeks later, and her serum CRE had returned to 0.8 mg/dL. ADAMTS-13 activity later resulted as 67%, but was drawn after first plasma exchange session. The complement serologies for aHUS were sent to an outside speciality lab for processing, but the blood work was not resulted to improper collection.


A 59-year-old Caucasian male presents with 2 months of intermittent nausea associated with abdominal pain, dysgeusia, weight loss, and diarrhea. He has no history of food, environmental, or drug allergies. The patient’s past medical history includes gastroesophageal reflux disease and colonic polyps found on screening colonoscopy. He had no significant family history including prior known allergic disorders. He denied any tobacco, alcohol, or illicit drug use. He was initially evaluated at an urgent care center and treated for oral candidiasis before referral to a gastroenterologist for persistent symptoms. As a part of the initial workup, he had an esophagogastroduodenoscopy (EGD) that revealed candidiasis in the esophagus, an ulcer in the stomach along with abnormal mucosa consistent with erosive gastritis, and duodenitis. Colonoscopy showed diffuse ulceration, granularity, erythema, and congestion with spontaneous bleeding throughout concerning for colitis. He had a CT of the abdomen/pelvis, which was unremarkable except for diverticula seen in the sigmoid colon and was started on prednisone 60 mg daily given concern for an unspecified colitis. After 1 month of treatment, the patient began feeling better with resolution of diarrhea, abdominal pain, and improvement in appetite. His steroids were tapered, and the patient presented with recurrence of symptoms a couple of months later.
At that time, repeat EGD showed diffuse continuous granularity, congestion, and ulceration of mucosa without bleeding compatible with gastritis. Diffuse granularity and ulceration was also noted in the duodenum with pathology confirming villous blunting and reactive epithelial changes. He then underwent capsule study that showed erosive gastritis, duodenitis, and stigmata of bleeding. There were patchy mucosal changes in the proximal jejunum suggesting mild jejunitis as well. On balloon enteroscopy, erythematous gastric nodules and severe duodenal inflammation were noted as well as erythema, scalloping, whitish exudate, and patches of villous blunting with a flat pink appearance were seen throughout the jejunum until the proximal ileum as seen in and . Laboratory results were unremarkable without evidence of peripheral eosinophilia or hypoalbuminemia, and he had fungal cultures and Helicobacter pylori testing that were negative.
On histopathologic examination, biopsy of the duodenum, proximal ileum, and random jejunum showed small intestinal mucosa with moderate eosinophilia characterized as more than 50 per high-power field in the lamina propria, focal fibrosis, and villous blunting and atrophy confirming the diagnosis of eosinophilic enteritis. Immunohistochemistry was performed for CD117, IgG4, CD3, and tryptase to rule out a mast cell disorder or increased intraepithelial T cells. Mast cells were noted to be mildly increased but without atypia. No dysplasia, neutrophilic cyptitis, or granulomas were identified. He was continued on oral prednisone at discharge but subsequently lost to follow-up after establishing the underlying etiology of his symptoms.


An 82-year-old male patient presented with chest tightness and shortness of breathing for 10 days. His past medical history included hypertension and old pulmonary tuberculosis. He suffered from productive cough for weeks and was referred to our center because of the worsening symptoms of dyspnea and lower leg edema noted over the past few days. On presentation, his consciousness was alert. Body temperature was 37.8 °C. Pulse was 136 per minute regular. Blood pressure was 164/90 mmHg. Oxygen saturation was 88%. Auscultation revealed decreased breathing sounds at left lung field and sonorous rhonchus at right lung field. X-ray of the chest showed left pneumothorax with collapse of left lung, and ground glass opacities in right lung field (), more in favor of inflammatory process at that time. He was admitted under the impression of right lung pneumonia with left pneumothorax and received chest tube insertion and empiric antibiotics treatment. However persistent air leak noted, he then received a chest CT for further survey. A chest CT showed nodular lesions over bilateral lung, with diffuse bone, left lower neck (), left suparclavicular, mediastinum, as well as right hilar () and lower abdominal lymph nodes metastases. Unknown primary malignancy with bilateral lung metastases, diffuse bony metastases with left supraclavicular and left neck lymph node metastases was impressed and further tissue proof for possible underlying malignancy was recommended. For this reason, an echo guided biopsy with left neck lymph node biopsy was arranged for further study because the surgical intervention was not recommended for the patient due to poor lung function while patient declined bronchoscopy biopsy either. A subsequent neck lymph node biopsy revealed metastatic adenocarcinoma, while immunohistochemical stain for thyroid transcription factor -1(TTF-1), and cytokeratin 20 (CK20) are all negative. Serum tumor markers were examined in an attempt to identify the primary lesion, revealing a PSA level of > 1,000 ng/mL (normal < 4.0 ng/mL) while CEA 2.7 ng/mL (normal < 5.0 ng/mL). Digital rectal examination showed an enlarged and hardened left prostate lobe. An abdomen CT disclosed 4.3 × 3.0 cm ill defined heterogenous mass lesion at lower lobe of prostate () with regional and non-regional lymph nodes () and bony metastases. The urologist was consulted, and transrectal ultrasonography (TRUS) showed irregular urinary bladder wall thickening with enlargement of prostate, hypoechoic nodule with increased vascularity in left peripheral zone of prostate. Meanwhile the patient refused further tissue proof due to his poor general condition. The pathologist was informed of the elevated serum PSA and further clinical data, then an additional immunohistochemical staining of the left neck lymph node biopsy with P504S was performed as was compared to the regular H&E stain (), the neoplastic cells expressed P504S diffusely (), a metastatic adenocarcinoma of prostatic origin was confirmed. However his condition went downhill rapidly, and after thoroughly discussion with the patient and his family, they decided to receive hospice care and refused further intervention.


A 56 year-old, previously healthy, Caucasian female was referred to our hospital for evaluation of thrombocytopenia and acute myocardial, renal, and splenic infarction. A few weeks prior to presentation, she developed acute left leg pain several weeks following surgery and physical therapy sessions for an occupational knee injury. She subsequently developed nausea and vomiting, anorexia, fevers and chills, associated with a dull, non-radiating left flank and left side chest discomfort. Her family history was notable for a mother with non-small cell lung cancer.
On physical examination, she was in no acute distress, afebrile, with a heart rate of 95 BPM and normal blood pressure. Cardiac examination demonstrated a normal rhythm, with no detectable murmurs or irregular sounds. A non-tender fullness was palpated in the right lower abdomen with some mild left upper quadrant tenderness. Non-specific induration was appreciated in the right calf without edema or venous stasis changes.
Initial laboratory studies were as follows: WBC 15.47 x 10/mcL, with a neutrophil count of 11.7 x 103/mcL; hemoglobin 13.3 gm/dL; platelet count 33 x 103/mcL; troponin 4.02 ng/mL; total CK 96 ng/mL, with a CK-MB 2.7 ng/mL and a relative index of 2.5; creatinine 0.8 mg/dL; international normalized ratio (INR) 1.56; PT 18.6 second; PTT 34.6 second; fibrinogen 209 mg/dL; fibrin degradation products (FDP) > 20 mcg/mL, and CA125 of 114 U/mL. Urinalysis showed moderate blood. Her EKG showed findings consistent with an acute, non-ST elevation myocardial infarction. CT imaging showed numerous large splenic, wedge-shaped hypodensities () with similar areas in the kidneys bilaterally (), most consistent with infarcts. Also noted was a 12.4 x 8 x 11 cm right pelvic, complex, cystic and solid appearing mass (). An echocardiogram was obtained and showed mild mitral regurgitation and a moderate sized vegetation on the anterior mitral valve leaflet (). Lower extremity Duplex showed no apparent thrombosis.
The initial working diagnosis was pelvic malignancy, endocarditis with multi-organ embolic infarction. She was started on appropriate antibiotics; however, over the ensuing days, laboratory studies showed worsening thrombocytopenia, progressive hypofibrinogenemia, and evolving anemia requiring transfusion of platelets, cryoprecipitate and fresh frozen plasma. In addition, she became increasingly weak, with dyspnea, bilateral leg discomfort and edema. A follow-up echocardiogram was unchanged; however, a repeat lower limb venous duplex showed new bilateral major DVT. Serial blood cultures remained negative.
We felt the patient had NBTE related to a pelvic malignancy. She was taken to the operating room for an exploratory laporotomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy. A 12 cm right ovarian cystic mass was completely removed, and pathology confirmed a stage 1C clear cell adenocarcinoma with positive peritoneal fluid cytology. Following surgery, the patient demonstrated steady improvement in her hematologic laboratory studies with normalization of her platelet count and fibrinogen by day 5. She was started on anticoagulation therapy on the third day post-surgery and discharged on warfarin with the intention of completing a 6 months course. A one month follow up echocardiogram showed near complete resolution of the mitral vegetations.
The patient completed 5 cycles of adjuvant chemotherapy and remained well for approximately 2 months, after which she developed extensive bilateral lower extremity DVT with clot up to and beyond the IVC filter. Further imaging showed evidence of a small pulmonary embolism, but no evidence of recurrent malignancy. She was switched to once daily enoxaparin. Several weeks later she was readmitted with acute dysarthria. Brain imaging revealed multifocal, punctuate infarcts, new ascites, evidence of peritoneal carcinomatosis, and further progression of venous thrombosis. No new valvular vegetations were evident by transthoracic echo. Platelet count and coagulation studies remained in the normal range. Cytology obtained from paracentesis confirmed recurrent malignancy. Given the patient’s markedly compromised state and rapid recurrence of malignancy, she was not felt to be a candidate for additional chemotherapy. A few weeks later, the patient died under the care of hospice services.


A 39 years old woman underwent quadrantectomy with SLNB (0/2) for a multifocal, grade 2, oestrogen receptor (ER) progesterone receptor (PR) positive and HER2 negative invasive lobular carcinoma of the right breast at 9 o’clock position in 2006. Post-operatively, she received adjuvant radiotherapy to the remainder of her right breast followed by tamoxifen and a GnRH agonist. Four years later, she presented with local recurrence in the same upper outer quadrant of her right breast. Staging investigations with CT and bone scintigraphy showed no metastatic disease. Lymphoscintigraphy, performed with scans at 0.5, 1.2 and 4 hours post-injection of 32 mBq of Tc-labelled nanocol, did not reveal any focal accumulation of radioisotope. She underwent completion mastectomy with axillary clearance and biopsy of the 3rd intercostal space IMLN. Histological examination revealed invasive lobular carcinoma with lymphovascular invasion and 27 negative axillary lymph nodes. The only positive node was the 3rd intercostal space IMLN. Adjuvant chemotherapy was given followed by aromatase inhibitor and GnRH agonist.


A 52 years old woman was treated by microdochectomy for single duct nipple discharge of her right breast followed by wide local excision and SLNB for high grade DCIS approximately 20 mm in maximum diameter, with micropapillary pattern and tumour free margins of greater than 10 mm, in 2003. There were four negative SLN’s retrieved. No adjuvant treatment was given. A surveillance mammogram, two years later, showed a tumour in the upper-inner quadrant of the same breast. Staging with CT and bone scintigraphy was negative. She underwent wide local excision with axillary lymph node sampling following a failed attempt to identify the sentinel node. The 2nd intercostal space IMLN was also biopsied. Histopathological examination revealed a 20 mm, grade 2, ER positive and HER2 negative invasive ductal carcinoma with metastasis in the IMLN. The axillary node sample was negative and there was no lymphovascular invasion. The patient was treated with adjuvant chemotherapy (FEC60 X 6 cycles), radiotherapy to the remainder of her right breast and anastrozole for 5 years.


A 13-year-old boy presented to the Pediatric Hematology/Oncology Clinic for evaluation of a lump on the right side of the skull, which was present for more than one year. The swelling was painful to touch with gradual increase in size. There was no history of trauma, fever, headache, vomiting, weight loss, visual disturbances or local redness. Patient was born after an uncomplicated pregnancy and delivery. His perinatal and past medical histories were unremarkable. There was no significant family medical history. He had normal growth and development and was up-to-date with his immunizations.
On physical examination, patient was well nourished and his vital signs were normal. Examination of the head revealed a swelling measuring 3 х 3 cm on the right parietal bone, hard in consistency, tender to palpation, with no other signs of inflammation. Examination of the ears, eyes, nose and throat showed no abnormalities. No lymph nodes were palpable in the neck, axillae or groins. Neurologic examination was normal. Rest of the physical examination did not reveal any abnormality.
Laboratory results showed: hemoglobin - 12.4 g/dL, white blood cell count - 6,900/µL, and platelet count - 281,000/µL. Skull X-ray revealed a lytic lesion of the right parietal bone (). Computerized tomography (CT) scan of the head demonstrated 2.5 cm destructive lytic lesion at the right parietal bone with soft tissue mass measuring 2.5 х 1.5 cm, extending to the extra-axial intracranial space. Initial diagnosis was suspicious for Langerhans cell histiocytosis. Bone scan and chest CT scan did not reveal any distant metastasis. Patient had resection of the lesion which was reported as grade 1 SEF. Post-operative head CT scan and MRI showed residual lesion of 8 х 6 mm at the inferior and posterior aspect of the previously excised mass. Considering this rare tumor's poor response to chemotherapy and radiation, a decision was made to do a total resection. A right parietal craniotomy with gross total resection of the tumor, followed by cranioplasty was performed. Pathology report was consistent with SEF as before.
Follow-up CT scan and MRI done after 6 months were negative for tumor recurrence. Ten months after the initial presentation, patient presented with an enlarging lump over the surgical site with headache, vomiting and 12 pounds weight loss. MRI of the brain revealed three new enhancing soft tissue lesions at the original tumor site and one at the deep posterior margin of the previous surgical cavity. Positron emission tomography (PET) scan did not show any evidence of distant metastasis. Patient underwent gross total resection of the tumor. Pathology confirmed the diagnosis of grade 3 SEF, more aggressive than the initial presentation (). Post-operative course was uneventful and MRI of the brain demonstrated no residual lesion. Patient was started on chemotherapy with Doxorubicin and Ifosfamide with Mesna. He also underwent external beam cranial irradiation and completed 6 cycles of chemotherapy. At the end of his last cycle of chemotherapy and 19 months after the initial diagnosis, he presented with headache, vomiting, back pain and weight loss. MRI showed cranial and spinal metastasis. There were new enhancing lesions in the right frontal lobe and tumor infiltration of the epidural and subarachnoid spaces from thoracic to sacral areas. Patient's clinical status deteriorated with obstructive hydrocephalus and paraplegia and he died within a month.


A 69-year-old man with mild liver dysfunction due to chronic type C hepatitis, underwent low anterior resection for rectal cancer in 2007. Pathological examination showed a well-differentiated adenocarcinoma invading the perirectal tissues, with metastatic involvement in 1 of the 15 lymph nodes removed (T4 N1M0/Stage IIIB), (). The patient underwent 5 cycles of tegafur-uracil plus oral leucovolon therapy (UFT/LV) as adjuvant chemotherapy without any adverse events. In 2008, abdominal computed tomography (CT) after UFT/LV showed swollen para-aortic and right lateral pelvic lymph nodes (). Thus, para-aortic and pelvic lymph nodes recurrence of rectal cancer was diagnosed. We started a FOLFOX-4 regimen in March 2008. However, the patient experienced G4 neutropenia and G3 fatigue (according to the Common Terminology Criteria for Adverse Events Version 4.0), and therefore had to discontinue FOLFOX-4. We started S-1 administration (100 mg/day twice on days 1 - 14, every 3 weeks) as salvage treatment in May 2008. Abdominopelvic CT after 5 cycles of S-1 showed reduction of the swollen para-aortic lymph nodes ().
Another series of abdominal CT performed after 10 cycles of S-1 monotherapy showed complete disappearance of swollen para-aortic and lateral pelvic lymph nodes (). Hence, response in this case was classified as a CR. The patient did not experience any adverse events during the S-1 monotherapy. No signs of recurrence or metastasis were noted 36 months after CR was confirmed.


A 51-year-old white female with no significant past medical history presented to her primary care physician (PCP) with a 1-month history of worsening lower abdomen pressure, and low caliber stools. She had no rectal bleeding, change in appetite or weight loss. Prior to this, she was treated with steroid injections for pain in the coccyx area for 2 years. She had a history of bladder repair. Family history includes father with lymphoma and mother with history of stroke. Physical examination including digital rectal exam was unremarkable except for mild lower abdominal tenderness.
She underwent a transvaginal ultrasound and was noted to have a 4.3 cm mass arising from cervix. A follow-up computed tomography (CT) scan of the abdomen/pelvis showed exophytic mass possibly arising from rectum. Endoscopic ultrasound (EUS) revealed a mass pushing the rectum from outside and a colonoscopy showed an indurated mass in the lower rectum/anal area but no mucosal lesions. EUS-guided biopsy was positive for squamous cell cancer (SCC). Further analysis of specimen for KRAS mutation was negative. Given squamous histology and no mucosal erosions/lesions within the bowel, it was felt to be a cervical cancer initially; therefore she was referred to a gynecologist. Biopsies of the endometrium and cervix were negative for malignancy. A positron emission tomography (PET) scan confirmed the disease and additionally demonstrated extensive paraesophageal and supraclavicular lymph nodal involvement. She underwent biopsy of her supraclavicular lymph node and was consistent with SCC.
She was commenced on chemotherapy with cisplatin and 5-flourouracil (5-FU) and after receiving two cycles, chemoradiation therapy was initiated due to bulky and painful anal mass. Post-chemoradiation, chemotherapy with cisplatin and 5-FU was resumed and she was able to finish a total of seven cycles. A PET/CT scan post-chemotherapy demonstrated no active disease. However a surveillance PET/CT scan 2 months later showed recurrence of the cancer. She was restarted on cisplatin and 5-FU but she had further progression of the disease. She was enrolled in a phase II trial with oral rigosertib but continued to have progressive disease. She was then commenced on weekly carboplatin and paclitaxel and continued for about 3 months interrupted only by hospitalization for rectal bleeding. She then underwent salvage debulking surgery with diverting colostomy for intractable pain, fecal incontinence that was complicated by rectovaginal fistula. She had severe neoplastic pain, requiring high doses of narcotics and intrathecal pain pump. She was then started on salvage regimen with mitomycin and 5-FU and received two cycles but with progression of disease. She received further radiation therapy for the localized disease and now she is receiving cetuximab without irinotecan due to low platelet counts. Patient is currently alive at 26 months after the diagnosis of anal cancer.


An 84-year-old white healthy male presented to his PCP complaining of anal bleeding and swelling in the anus. On physical exam, the patient had palpable enlarged inguinal lymph node in the left groin in addition to palpable anal mass. He was referred to the rectal surgery clinic where anoscopy was performed. An anal mass was identified, biopsies were obtained and the pathology demonstrated SCC. The patient underwent staging workup with PET/CT scan which revealed bilateral inguinal, para-aortic and mediastinal lymphadenopathy in addition to local uptake. After a lengthy discussion, he was commenced on concurrent chemoradiation (CCR) therapy with 5-FU and mitomycin. He developed pancytopenia and severe anal skin burn from chemoradiation requiring prolonged break between the two chemotherapy cycles. He had a PET/CT scan 3 months after completion of chemoradiation therapy that demonstrated complete resolution of uptake in the primary mass in addition to decreased size and uptake in the inguinal and mediastinal lymphadenopathy. After a detailed discussion with the patient about the possibility of persistent disease, he opted for observation only.


A 38-year-old South-Asian female was admitted with worsening cough, shortness of breath and fever for three days. She had these symptoms for over one year. She was afebrile at the time of examination and her vitals were normal and stable. On physical examination, chest veins were prominent throughout and on inspection, the auscultation was notable for stridor.
Basic labs were obtained that revealed a hemoglobin of 10.6 g/dL, white blood count of 18.4 g/dL with 84% neutrophils. The patients' potassium level was 3mEq/L, Lactate Dehydrogenase (LDH) was 1134 U/L and C-reactive protein (CRP) was 15 mg/dL. The rest of the laboratory results were unremarkable. A chest x-ray was obtained that showed opacification concerning for mass over the right upper heart border (Figure ). The computed tomography (CT) scan demonstrated a large, ill-defined, enhancing mediastinal soft tissue mass (11 X 10cm) encasing the heart and major vessels, with interval increase in size as compared to a previous examination performed two months ago (9 x 6 cm). Additional findings included multiple parenchymal deposits in both lungs (Figure ). The features raised suspicion of a lymphoma. The patient underwent a CT-guided biopsy of the mass and was hospitalized for further monitoring. The patient remained stable for two days before developing hypoxic respiratory failure along with fevers of 101-102°F. The patient demonstrated tachycardia with a heart rate of 110/min and examination was significant for stridor. The pathology report on biopsies showed a chronic granulomatous inflammation with septate fungal hyphae pointing towards invasive aspergillosis (Figure ). An echocardiogram was obtained that showed an ejection fraction of 25-30%, severe global hypokinesia, moderate mitral regurgitation, pulmonary artery systolic pressure of 40 mmHg and an enlarged echogenic density in the right atrium. The patient was emergently transferred to the intensive care unit (ICU) and was immediately started on antifungal treatment with amphotericin and fluconazole. Unfortunately, the patient became dyspneic and hemodynamically unstable later that night. The patient was then intubated and started on three different vasopressors (epinephrine, norepinephrine, and dopamine) to keep the patients' mean arterial pressure (MAP) >65mmHg. The patient underwent cardiac arrest with pulseless electrical activity and cardiopulmonary resuscitation was carried out for 30 minutes before the code was called off.
The patients' past medical history was significant for suspected pulmonary tuberculosis with prolonged symptoms of cough and fever. The patients' Acid- fast bacilli (AFB) smears at that time were negative; however, she was treated with Anti-Tuberculosis Therapy (ATT) due to clinical suspicion. Her chest x-ray improved after completion of her therapy. The computed tomography chest obtained post therapy revealed fibrotic calcific foci with partial loss of lung parenchyma confirming the suspicion of tuberculosis. The patient then presented a few months later with chest pain and hemoptysis to another hospital and a high-resolution CT scan was performed that revealed patchy nodular pulmonary parenchymal changes in both lungs, extensive mediastinal and bilateral hilar lymphadenopathy, extensive lymphadenopathy in posterior mediastinum and possible left breast mass. A biopsy of the breast mass was performed that showed normal tissue. The patient underwent mediastinal incisional biopsy of the posterior mediastinal lymph node by a cardiothoracic surgeon and the biopsy was significant for chronic granulomatous inflammation and the patient was started on re-treatment regimen for tuberculosis. The patient again presented a month later with stridor, dysphagia, and cough. The patients' ATT was continued and she was also started on prednisolone 20 mg twice daily, the rationale of which was unknown, continued to experience symptoms of nausea, vomiting, undocumented fevers. The patients' prednisone dose was decreased to 15 mg twice daily and was then presented to our hospital after few weeks with aggravating symptoms as described above.


A 62-year-old Japanese woman was referred for bilateral dry eyes, with Schirmer’s test results of 0 mm for both eyes. Four years previously, she had been diagnosed with primary rheumatoid arthritis (RA) and secondary Sjogren’s syndrome. She was being treated with 6 mg of methotrexate. CT scans appeared normal when she was first diagnosed with RA. Just prior to her dry eye referral, her previous hospital found C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels to be significantly increased (CRP of 11.83 and LDH of 952), leading to a suspicion of an underlying malignancy. A CT scan was done, and some lung opacities were found, but biopsies of bone marrow, pleural fluid and cerebrospinal fluid (CSF) all revealed no neoplastic activity.
While being treated for dry eye at our hospital, emergent hyperemia presented in the right eye coupled with fever and photophobia, for which she was admitted to the hospital. In the inpatient ward, hemorrhagic hypopyon that showed niveau-like hypopyon with hemorrhage as reported in previous case [] was seen on slit lamp(Fig. ). A distinct herpetic corneal lesion (Fig. ) were noted via fluorescein staining. Keratic precipitates were noted, but no synechiae. HSV was specifically identified in the right eye via Checkmated Herpes-eye®, (Wakamoto Co., Ltd., Tokyo Japan). Corneal smear was done to rule out bacteria as a potential cause. Right eye visual acuity was found to be 20/500, while left eye visual acuity remained 20/20. Right eye intraocular pressure (IOP) was 16 mmHg and left eye IOP was 18 mmHg. The anterior segment of the right eye presented with hyperemia, dendritic keratitis, and intracameral fibrin deposits (Fig. ). Posterior segment appeared normal. Anterior segment optical coherence tomography (AS-OCT) further illustrate the fibrin deposits and hemorrhagic hypopyon (Fig. ). Body temperature was elevated to 38.5 °C, with a white blood cell count (WBC) of 10.4 × 103/μL (with neutrophils being 64.3%, lymphocytes 16.5%, monocytes 16.8%, eosinophils 1.9%, and basophils 0.5%) Treatment with topical acyclovir ophthalmic ointment (5 times daily), topical levofloxacin (5 times daily) and oral valacyclovir (3 times daily). Two days later, the dendritic keratitis began to regress.
By day 5 of treatment, the dendritic keratitis, fibrin, hypopyon had regressed, with only superficial, punctate keratitis and Descemet membrane folds remaining. WBC normalized, CRP dropped to 9.72 and body temperature dropped to 36 °C. The right eye’s visual acuity recovered to 20/200, which was comparable to baseline on account of a cataract. Three weeks after hospitalization, symptoms had completely regressed; slit-lamp findings revealed no findings indicative of herpetic keratouveitis or recurrent hypopyon.
Nearly 3 months later, a fever and corneal opacities reoccurred. Again, a characteristic herpetic dendritic lesion, superficial punctate keratitis, and intracameral fibrin deposits were noted (Fig. ). WBC count remained normal, diminishing suspicion of RA flare-up. Due to the previously elevated LDH levels and previous rare viral presentation, malignancy was again suspected. A positon-emission tomography-computed tomography (PET-CT) showed significant diffuse lung opacities whereafter a lung biopsy was performed to confirm an intravascular B cell lymphoma (Fig. ). Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen was begun immediately, and the corneal lesions and the lymphoma both went into complete remission. Over a year and a half later, there is still complete remission of the cancer and no corneal lesions or ocular symptoms (Fig. ).


A 10-year-old boy visited the Department of Pedodontics with the complaint of being unable to chew on his right side. Upon examination, the lower arch contained the following teeth: 36, 35, 34, 73, 32, 31, 41, 42, 83, and 46 (). The upper arch contained teeth consistent with the intertransitional period, except that 14 had erupted (). Upon history taking, it was gathered that 84 and 85 had been extracted a year ago due to extensive caries and severe pain. An orthopantomograph (OPG) revealed half root completion of the unerupted 44 and 45 (). It was decided to construct a LHLD (functional lingual arch with hinge-type lockable dentulous component) in order to maintain the edentulous span until the eruption of 44 and 45, and to relieve the child of his chewing disability. After band adaptation on 36 and 46, alginate impressions were made of both the arches, into which the prepared bands were placed ( and ). Casts were poured with dental stone. A lingual arch incorporated with two molar tubes (on the edentulous side) was fabricated using 0.9 mm wire on the lower cast (). Wax up was done on the edentulous span containing artificial molar teeth (to replace 84 and 85), such that the molar tubes were incorporated into the wax up in order to later serve as hinges for the dentulous component. On the buccal side of the dentulous component, another molar tube was placed, such that it was parallel and in alignment with another buccal tube welded on the buccal surface of the molar band ( to ). The lingual arch was then soldered to the bands ().
Plaster blockout of the undercuts and buccal tubes was done (). Acrylization was carried out using self-cure acrylic by the putty method. An index was made of the wax up () using addition silicone (Elite HD, Zhermack, Germany), following which the cast was dewaxed (). Artificial teeth were incorporated into the index () and self-cure acrylic was mixed with monomer and placed into the index. The index was reseated on the edentulous ridge on the cast until the acrylic mixture had completely polymerized (). An "Angry Birds" sticker was laminated and placed on the buccal surface of the dentulous component and covered with a thin layer of clear acrylic. The appliance was then gently removed from the cast ( and ).
The tubes on the buccal surface were incorporated in order to pass the locking wire (0.64 mm) that formed the locking component of the appliance ( and ). The efficacy of the hinge (molar tubes attached to the lingual arch) was verified by rotating the dentulous component around its hinge axis ( and ). Finishing and polishing was carried out for the acrylic and metal components. The appliance was evaluated for any mucosal interferences or occlusal disharmonies, following which the appliance was inserted intraorally by cementing the bands onto 36 and 46 using luting glass-ionomer cement ( and ). The patient was recalled the next day for a check-up, following which another general evaluation was done after a week.


In September 2015, a 52-year-old healthy male was seen in the outpatient department for slow progressive of dysphagia, bilateral eyelids ptosis, and generalized fatigue. History goes back to twenty years prior to his presentation when he started having trouble swallowing which slowly worsened over the years. Later on, he noticed that his upper eyelids have drooped. And around one year earlier, the patient started experiencing difficulty standing from the sitting position, and trouble climbing the stairs associated with an intermittent funny feeling in his right upper and lower extremities that he described as mild tingling and a sensation of numbness. The patient denied frank weakness but admitted to getting tired quickly. The patient had no previous medical history. He never smoked cigarettes, did not consume alcohol, and has never used illicit drugs. Upon presentation, the patient was in no distress. He was afebrile, with a blood pressure of 123/79 mmHg and a heart rate of 72 beats per minute (bpm). On physical examination, bilateral upper eyelids ptosis was noted. Otherwise, neuromuscular examination including cranial nerves examination, cerebellar function, sensation, and motor power was intact. Deep tendon reflexes in upper and lower limbs were normal. There was no muscles atrophy or tenderness, no fasciculation or twitching was noted. Laboratory tests did not show any abnormality, except for elevated creatine kinase and aldolase levels (CPK of 487 IU/L and aldolase of 8.6 U/L). The magnetic resonance imaging of the brain and whole spine was grossly insignificant. Urinary drug screening test was irrelevant and the patient denied taking any medication including herbal medicines and dietary supplements making a toxic or drug-induced etiology improbable. Thyroid stimulation hormone (TSH) level was normal ruling-out hypo- and hyperthyroid- myopathy. Anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) were negative too, making autoimmune diseases less likely. Likewise, there were no autoantibodies against the acetylcholine receptors antibodies (AChR-Ab) or against the muscle-specific receptor tyrosine kinase antibody (MuSK-Ab) and an electrophysiologic study of the nerves and muscles failed to reveal any disease ruling-out myasthenia gravis. Finally, because the patient noted similar symptoms in his elder sister, an extensive genetic testing was conducted and the patient was found to have only one copy of the survival motor neuron 1 gene (SMN1) confirming the diagnosis of spinal muscular atrophy disease (SMA).


A 42-year-old man presented with swelling at the medial canthus of the left eye associated with epiphora. The swelling appeared four years back and gradually increased in size. There was no history of dacryocystitis, mid-facial trauma, surgery, or bloody tears. On examination, there was an immobile, subcutaneous, noninflammatory mass below the left medial canthal tendon (Figure ). Regurgitation test was negative on the left side. There was a delay in dye disappearance and lacrimal irrigation showed blockade at the nasolacrimal duct. An otorhinolaryngology consult and examination did not show any nasal cyst or polyp and there was no evidence of paranasal sinusitis.
A computerized axial tomography (CAT) scan revealed a 2.0 x 2.0 cm non-enhancing, low-density, cystic lesion at the inferomedial margin of the left orbit. There were no signs of bony erosion consistent with idiopathic acquired dacryocystocele (Figure ).
The patient was treated conservatively with topical antibiotics and sac massage for one week, but there was no improvement. The patient underwent external dacryocystorhinostomy (DCR) with silicone tube intubation. During the surgery, a clear, yellowish fluid was drained from the lacrimal sac. The lacrimal sac was biopsied and the fluid was sent for culture. The culture of the fluid was negative and histopathology of the sac showed a squamous epithelium with goblet cells. There were no neoplastic cells, confirming the diagnosis of idiopathic acquired dacryocystocele.
The patient’s symptoms of epiphora resolved right after the surgery. The silicone tube is in place and it will be removed after six months.


A 77-year-old female patient with a history of chronic obstructive pulmonary disease and paroxysmal atrial fibrillation presented to our emergency department with collapse and was diagnosed with sick sinus syndrome. Before pacemaker implantation, echocardiography showed normal dimensions of both atria and ventricles and normal systolic left and right ventricle (RV) function. A DDD-R pacemaker was successfully implanted using active-fixation leads without any acute complications. The day after implantation, sensing and pacing parameters were normal and unchanged. Chest radiography then showed a normal position of both leads (Fig. a, b). Subsequently, the patient was discharged the same day in good clinical health.
Four days later, however, the patient was readmitted because of sharp chest pain, unrelated to physical activity or posture. Pacemaker data showed a marked switch from bipolar to unipolar lead pacing and malcapture of the RV lead at maximal pacemaker output. Chest radiography revealed an altered RV lead position (Fig. c, d). Echocardiography suggested a perforation of the RV lead through the RV apex but without pericardial effusion (Fig. e and online video). This raised doubt as to whether the lead tip lay in the pericardial space. Ultimately, thoracic computed tomography (CT) showed that the lead went through the myocardium (Fig. f, g). The patient was subsequently transferred to a specialized pacing lead extraction center with surgical backup, where the RV lead was repositioned uneventfully.


A 55-year-old white man, who was a chronic tobacco smoker, came to our otorhinolaryngology department because of a pedunculated painful lesion on his tongue. He was married and was living with his wife. His medical history included hypertension which is controlled with an angiotensin-converting enzyme inhibitor. On clinical examination, he had a performance status of 1, his blood pressure was 120/70 mmHg, temperature was 37.2 °C, and heart rate was 90 beats/minute with negative dipstick. An oral examination showed a large exophytic lesion occupying the anterior two thirds of the right side of his tongue (Fig. ). Neurological examination, fiber optic nasopharyngoscopy, and laryngoscopy were normal. Complete blood count was normal with a hemoglobin level of 12 g/dL, a platelet count of 300 × 109/L, and white cell count of 5 × 109/L. His renal function was normal with a creatinine of 0.8 mg/dL. His corrected serum calcium was 2.39 mmol/L and lactate dehydrogenase (LDH) level was 202 UI/L. Aspartate aminotransferase, alanine aminotransferase, and bilirubin were normal. A biopsy of the lesion was taken. Pathologic examination showed a poorly differentiated carcinoma, including a sarcomatoid component represented by spindle cells. Subtotal glossectomy with neck dissection were planned after a staging positron emission tomographic-computed tomography (PET-CT) scan. The PET-CT scan revealed a tongue lesion, bilateral pulmonary metastases, muscle metastases, and a left kidney mass (Figs. and ). An abdominal computed tomography (CT) scan confirmed the presence of a 13 cm left kidney mass.
Our patient was referred to our oncology department. A detailed medical history was performed, and he described an episode of macroscopic hematuria. A physical examination revealed a subcutaneous nodule in his right axillary region. He had a performance status of 1, and arterial pressure was normal. An immunohistochemical evaluation was performed, and it was positive for Pax 8, CD10, and AE1/AE3 and negative for CK20, CK7, and thyroid transcription factor 1 (TTF1). This result is compatible with a metastasis from a primary renal cell cancer. A biopsy of the renal lesion was performed. Morphological and immunohistochemical findings were consistent with a high-grade unclassified RCC.
The tongue lesion doubled in size within 2 weeks. Treatment was initiated with sunitinib 50 mg/day, on a schedule of 4 weeks on treatment followed by 2 weeks off. After 2 weeks of treatment, the size of the tongue lesion as well as the size of a subcutaneous nodule had decreased a little (Fig. ). Sunitinib treatment was discontinued after one cycle because of an unexplained fever. Subsequently, the mass on our patient’s tongue grew and protruded outside his mouth, and caused difficulty in swallowing. CT imaging showed progression of the disease on his tongue, lung, lymph nodes, and muscle. He started second-line systemic therapy with doxorubicin and gemcitabine, but he died 10 days later because of a hemorrhagic complication of the tongue lesion.


Forty three-year-old white woman was diagnosed with metastatic, K-RAS wild type, colon cancer in July 2013 with liver metastases. She underwent nine cycles of mFOLFOX6 with Bevacizumab. Oxaliplatin was then discontinued due to grade II neuropathy. She was then treated with 5-FU and Bevacizumab. She then progressed and subsequently received ten cycles of FOLFIRI and Bevacizumab. Her disease progressed again and then switched to FOLFIRI/Cetuximab. Again, her disease progressed so she was started on FOLFOX–Bevacizumab.
Patient tolerated the first three cycles well and had no neuropathy. When she presented for cycle 4, she was found to have severe thrombocytopenia of 6000 k/μL. Peripheral smear revealed large platelets and no schistocytes. She was not prescribed any new medications. Using the Naranjo adverse drug reaction probability scale, the diagnosis of oxaliplatin-induced thrombocytopenia was probable. She was treated with steroids for suspected ITP. Count recovered above 100 k/μL within 1 week.
She was rechallenged with mFOLFOX6 with Bevacizumab when her platelet count recovered. The next day her count dropped from 234 k/μL to 9 k/μL when she presented with epistaxis. At this point, her Naranjo score was nine, suggesting oxaliplatin as a definitive cause of her thrombocytopenia. She was treated with IV immunoglobulins, steroids and her counts recovered. Oxaliplatin was dropped with her subsequent cycles, and platelet count remained within normal range (Fig. ).


A 9-year-old Chinese girl was admitted to our unit due to episodic fainting attacks associated with sweatiness and decreased consciousness persisting for a year with aggravation for the previous 1 month. Hypoglycemia with a serum glucose level of 2–3 mmol/L was confirmed when the symptoms appeared and was resolved with intravenous glucose infusion. The fasting plasma blood-glucose level (FBG) was 1.84 mmol/L, insulin level was 8.2 mU/L, and insulin/glucose ratio was 4.46. An abdominal dynamic contrast-enhanced magnetic resonance imaging (MRI) scan revealed a tumor at the tail of the pancreas (Fig. A, B). There were no abnormal findings on ultrasonography of the thyroid gland and adrenal gland. Considering the case history, laboratory data, and imaging findings, the patient was diagnosed with insulinoma in the tail of the pancreas, and robot-assisted, spleen-preserving laparoscopic distal pancreatectomy was planned.
The patient was given a 5% glucose intravenous infusion constantly and slowly to prevent hypoglycemia. The robot was placed at the head of the patient. The assistant surgeon was positioned between the patient’s legs, and the surgical nurse stood at the right side of the patient. The patient’s blood glucose level was monitored and kept above 3.4 mmol/L throughout the whole procedure.
The pneumoperitoneum pressure was 12 mmHg. A total of four trocars were used. The first trocar (10 cm) was inserted 5 cm below the umbilicus. The other three trocars were introduced under laparoscopic watch into the left anterior axillary line at the umbilical level (8 mm), the right anterior axillary line 2 cm below umbilical level (8 mm), and the left midclavicular line 3 cm below the umbilical level (12 mm; Fig. ).
The surgical procedure was performed as follows: After the gastrocolic ligament was dissected with an ultrasound knife, the posterior gastric wall was sutured to the round ligament of the liver with 4-0 prolene in order to expose the pancreas. Then, the gastrocolic ligament and splenocolic ligament were dissected to move the splenic flexure of the colon away from the surgical field. A hard tumor was seen at the tail of the pancreas, with a diameter of 2 cm, purplish color, and a clear margin (Fig. A). Laparoscopic ultrasonography showed main pancreatic duct involvement, and no other pancreatic lesion was found. The spleen vein was seen embedded with the pancreatic parenchyma; both the surgeon and assistant separated them carefully, patiently, and gently. Then, the pancreatic capsule was dissected along the lower edge of the pancreas with a hook knife, and the splenic vessels were separated and divided from the pancreatic cyst to avoid bleeding caused by adherence (Fig. B). After complete isolation of the tail of the pancreas from the spleen, the ECHELON endoscopic linear stapler (EC 60A, Johnson & Johnson, OH, USA) was used to transect 1 cm proximal to the tumor (Fig. C). The antecedent 4-0 prolene in the posterior gastric wall was cut, and a suction drain was placed through the lesser sac to the transected pancreas. Fast–frozen pathology indicated a neuroendocrine pancreatic tumor, or insulinoma, considering the clinical symptoms. The total operating time was 155 min, in which the pneumoperitoneum time was 120 min with an estimated blood loss of 10 ml.
The urinary catheter was removed on day 1. The gastrointestinal decompression was successfully removed on day 3. The drain was clean and removed on day 7 (Fig. ). The patient was given solid food on day 7 and discharged to home on day 8 after abdominal MRI showed no abnormalities. Her FBG was kept above 3.4 mmol/L pre-operatively, 12 mmol/L after removal of the tumor, and 9 mmol/L after the surgery.
The post-operative pathology results indicated a neuroendocrine tumor in the pancreas tail, 2 × 2 × 1.2 cm, mitosis count 3/10 HPF, IHC: Ki-67 (+10%), CgA (+), Syn (3+), SSTR2 (−), CK (+), CD56 (+), SSTR3 (+), SSTR1 (+), β-catenin (+), CD117 (-), and Grade 2, with local nerve involvement.


A 61-year-old male, former cigarette smoker, with diabetes mellitus and a past medical history of Fobi-Capella Roux-en-Y gastric bypass for glycemic control in an outside institution, developed an incisional hernia 2 months after the operation. Nineteen months after the procedure, the patient was then submitted to an upper gastrointestinal endoscopy in our service for further evaluation of the hernia before repair surgery. At the time, he was asymptomatic with no significant findings in the clinical examination besides a 10.0-cm hernia over the abdominal midline incision. The endoscopic exam revealed a vegetating, friable lesion in the gastric pouch, near the gastroesophageal junction, measuring approximately 2.0 cm in the greatest diameter. A biopsy of the lesion was performed.
The hematoxylin-eosin slides of the endoscopic biopsy revealed a neuroendocrine neoplasm. Ancillary immunohistochemistry (IHC) studies showed positivity for cytokeratin pool AE1/AE3, cytokeratins 8/18, CD56, synaptophysin, chromoganin A, and Ki-67 index of 30% of the neoplastic cells. Based on those findings, a diagnosis of neuroendocrine carcinoma according to the 2010 World Health Organization (WHO) classification was rendered. For staging purposes, computed tomography and an endoscopic ultrasound were performed, which showed a paraesophageal adenomegaly and no signs of invasion of the muscularis propria (cT1 cN1 cM0—TNM 8th edition). The patient was then submitted to total gastrectomy with D2 lymph node (LN) dissection and hernia repair.
Grossly, the gastrectomy product showed a 2.0 × 1.5 cm elevated, vegetating lesion. Microscopic examination revealed a MANEC (WHO 2010), constituted by a mixed adenocarcinoma (tubular and poorly cohesive) in association with a neuroendocrine carcinoma (), constituting 40% and 60% of the lesion, respectively. The tumor infiltrated on the submucosa, and lymphovascular invasion was detected. The surgical margins were free of tumor cells. The LN dissection revealed 24 LNs, with 2 of them from the lesser curvature compromised by the neoplasia. Surprisingly, one of the LNs was infiltrated by a pure neuroendocrine carcinoma whereas the other was compromised by a pure tubular adenocarcinoma component (). The IHC panel findings from the surgical specimen were similar to the biopsy findings. The hernia sac showed no histologic abnormalities.
Laboratory and imaging postoperative examinations did not reveal residual or metastatic disease. A 12-cycle course of adjuvant chemotherapy including folinic acid, fluorouracil, and oxaliplatin (FOLFOX) was initiated, started at nearly 3 months after the surgery, and the patient tolerated it well.
Almost 3 years after the gastrectomy, the patient had to undergo a small bowel resection due to an acute obstruction caused by adhesions. Three years later, he presented with an expansive retroperitoneal formation on imaging follow-up exams. A computed tomography–guided biopsy of this lesion revealed infiltration of nodal and soft tissues by a pure adenocarcinoma, confirming the recurrence of the disease, this time as a single-component neoplasm. At the time of writing, the patient is now about to start a new course of systemic treatment.


A 25-year-old African-American female presented to our clinic with asymptomatic lesions linearly arranged over her left upper extremity. The initial lesion first appeared fifteen years ago and new lesions gradually appeared over time. She denied joint pain and/or a history of infections prior to lesion development. Her past medical history was significant only for posttraumatic distress disorder and depression. There was no personal or family history of psoriasis or other dermatologic disease. Prior to presentation in our clinic, she had a skin biopsy of the right forearm which showed chronic spongiotic dermatitis with parakeratotic foci and superficial perivascular mononuclear infiltrates. No deep dermal or periadnexal infiltrates were seen and periodic acid-Schiff staining was negative for fungal organisms. Based on the results, both lichen striatus and linear psoriasis were considered as potential diagnosis, and she was started on high-potency topical steroids. A month later, the patient was referred to our clinic when she failed to respond to treatment.
Physical examination revealed hyperkeratotic and scaly gray papules coalescing into a linear plaque of the right dorsal fifth finger extending medially to the right elbow (). Of note, scaly papules were also present on a tattoo above the right elbow (). There was no nail or palmoplantar involvement. The differential diagnosis included linear psoriasis and ILVEN. The isomorphic reaction seen within the patient's tattoo (Koebner phenomenon) favored a diagnosis of psoriasis. A skin biopsy and electrodessication of one papule on her right dorsal fifth finger were performed. Histological examination of the specimen revealed parakeratosis with uniformly acanthotic epidermis (). At a follow-up visit 2 weeks later, the patient developed new papules with similar morphology in the area that was previously electrodessicated (). This new episode of Koebnerization and histological findings further supported our diagnosis of linear psoriasis and the decision was made to initiate treatment with ixekizumab, a monoclonal antibody targeting interleukin- (IL-) 17A. Four months later and after 8 doses of ixekizumab, we observed almost-complete resolution of the cutaneous lesions (Figures and ).


A 54-year-old asymptomatic male underwent routine screening colonoscopy. A 2.0 cm polypoid, nonobstructing, ulcerated lesion was seen just inside the ileocecal valve (). A 1.0 cm portion of the polyp was removed with a hot snare and submitted for pathologic evaluation.
Four micron thick sections were cut from paraffin blocks of the terminal ileum and stained with hematoxylin and eosin (H&E) and immunostains for CD20, CD3, CD30, CD15, CD45, CD21, EMA, BCL6, OCT2, PAX5, IgD, PD-1, and kappa and lambda immunoglobulin light chains. Sections from the ileal lesion showed expansion of the submucosa by a lymphohistiocytic infiltrate with a vaguely nodular pattern (). Unremarkable reactive secondary lymphoid follicles were seen adjacent to the nodular area. The nodules contained scattered large atypical cells in a background of small lymphocytes and occasional histiocytes (). The large cells showed features characteristic of lymphocyte predominant (LP) cells, including multilobated nuclei with watery chromatin, single central nucleoli, and sparse cytoplasm.
At low power, immunohistochemical stains showed that the nodules contained mostly CD20-positive B-cells that coexpressed IgD and were associated with expanded CD21-positive follicular dendritic cell meshworks (). At higher power, the large atypical cells were observed to express CD45, CD20 (), PAX5 (), OCT2 (), and BCL6. Kappa and lambda stains showed them to be kappa light chain-restricted. They were negative for CD30, CD15, and EMA. The large cells were rosetted by CD3-positive and PD-1-positive T-cells (). These immunophenotypic findings confirmed the diagnosis of NLPHL.
There was no evidence of disease at other sites (clinical stage IEA). The patient had a complete response to chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Colonoscopy performed 24 months after diagnosis was normal, and imaging studies performed 30 months after diagnosis revealed no evidence of disease.


A 63-year-old female patient presented with acute dyspnea to the emergency department. She said she had been having mild dyspnea for 6 months, but did not visit a doctor because the symptom occurred intermittently. Her initial vital signs were blood pressure (BP) of 200/100 mm Hg, heart rate of 124 beats/min, respiratory rate of 23/min, and oxygen saturation of 90%. An initial chest X-ray revealed pulmonary edema and mild cardiomegaly with a cardiothoracic (CT) ratio of 54%. Laboratory testing revealed a slightly elevated white blood cell count of 10,800/μL, and hemoglobin and C-reactive protein levels were within the normal range. The level of pro-brain natriuretic peptide was elevated at 1326 (21.4–189.2) pg/mL. Cardiac enzymes were within normal limits. She had been diagnosed with hypertension 20 years prior, but she had not taken hypertensive medication for the last 10 years. Her systolic BP decreased to 130 to 150 mm Hg several hours later, without specific medication. Electrocardiography showed sinus tachycardia of 124 beats/min and inverted T-waves in the precordial leads. Transthoracic echocardiography showed moderately reduced left ventricular (LV) ejection fraction (37% by Simpson's biplane method; Supplementary video 1) with LV enlargement (LV end-diastolic dimension of 6 cm). Septal and LV posterior wall thicknesses were 9.7 to 10.2 mm, and LV end-diastolic volume (EDV) increased (130 mL by biplane disc-summation method, 80 mL/m2). The left ventricular mass index (LVMI) was also elevated to 190 g/m2. The average global longitudinal strain was −8.6%. There was no evidence to suspect valvular heart disease.
Pulmonary edema improved rapidly with loop diuretic. Coronary angiography was performed to identify ischemic heart disease. The angiography revealed abnormal courses of anomalous coronary arteries, but no significant stenosis in epicardial coronary artery. The ramus intermedius artery did not taper along the course at all, and drained into a certain cavity (Fig. A). The right coronary angiography also showed the same pattern as the intermedius artery (Fig. B). After dual coronary injection, we identified that the 2 arteries joined near the termination point and seemed to drain together into the LV cavity (Fig. C; Supplementary video 2).
We performed cardiac computed tomography (CCT) and focused echocardiography to check the exact entering point. CCT showed a clear-cut view of the anomalous coronary artery course and the entering point, the basal LV (Fig. ). Echocardiography showed a small defect in the basal inferior wall and an abnormal blood flow through the defect, occurring only during diastole (Fig. A; Supplementary video 3). The peak flow velocity in early diastole was about 2 m/s (Fig. B). Finally, the patient was diagnosed with a CAF with connection between the right coronary artery, intermedius artery, and the LV cavity. The amount of shunt seemed to be too small to cause heart failure. We chose to administer medical treatment with angiotensin-converting-enzyme inhibitor (ramipril 2.5 mg once a day), loop diuretic (furosemide 20 mg twice a day), and spironolactone (12.5 mg once a day). After discharge, her BP was tolerable, the congestion had completely disappeared, and her CT ratio had decreased to 48%. A low dose beta-blocker (bisoprolol 0.625 mg once a day) was added to her medication regimen. Four months later, LV ejection fraction improved to 51% (Supplementary video 4) and also the average global longitudinal strain to −12.2%. LV end-diastolic dimension decreased to 5.2 cm, and LVEDV was normalized to 86 mL (54 mL/m2).


A 29-year-old woman with no prior medical history presented with a new black spot in her right eye and wavy lines in her left eye. Best corrected Snellen visual acuity was finger count in the right eye and 20/40 in the left eye. Anterior chamber examination was unremarkable and trace vitreous cell was noted in both eyes. Fundoscopic exam revealed multiple, small, punched-out variably pigmented lesions in the posterior pole of both eyes with scattered peripheral lesions (). OCT (Spectralis HRA + OCT, Heidelberg Engineering, Inc., Heidelberg, Germany) demonstrated RPE disruption and deposition with intraretinal fluid with retinal atrophy in the right eye () and RPE disruption with subretinal and intraretinal fluid in the left eye (). OCT-A (RTVue-XR Avanti, Optovue, Fremont, CA) at the level of the RPE disruption in both eyes revealed increased abnormal flow consistent with bilateral CNV (). FA (Optos, Optos Inc., Dunfermline, United Kingdom) demonstrated late leakage corresponding to the CNV (). The patient received bilateral intravitreal injections of bevacizumab and was lost to follow-up after a single treatment.


A 26-year-old man arrived at the emergency department with a seven-day history of hematemesis and melena. He had no previous medical history and did not drink alcohol or used any illicit drug or medication.
Physical examination on admission showed blood pressure of 100/60 mmHg, a temperature of 36°C (96.8°F), a pulse rate of 90/min, and a respiratory rate of 22/min; his height was 1.75 m, weight 98 kg, and BMI 32 kg/m2. He experienced pain with deep palpation in the epigastrium and no organomegaly or lymphadenopathy was identified. The left scrotal sac was enlarged and indurated and there was a mass in the left scrotum that was indistinguishable from the left testis and provoked displacement of structures of the penis and right testis (the right scrotum was empty). No inguinal lymphadenopathy was identified.
Laboratory tests revealed normal liver function. Hemoglobin was 9.13 g/dl, MCV was 87.9 fL, WBC was 11.9 K/uL, neutrophils were 9.81 K/uL, lymphocyte count was 1.59 K/uL, and platelet level was 252 K/uL. Serum glucose level was 106 mg/dl, BUN was 38 mg/dl, creatinine was 0.9 mg/dl, and calcium was 8.9 mg/dl. Serum alpha-fetoprotein (AFP) level was 17,090 ng/mL, lactate dehydrogenase was 1480 U/L (normal range: 91–180 IU/L), and human chorionic gonadotropin level was 287.4 IU/mL.
After resuscitation with crystalloid solutions, he underwent upper endoscopy. The gastroenterologist found abundant active bleeding, for which orotracheal intubation was decided to provide airway protection. The patient was transferred to the intensive care unit. A second upper endoscopy revealed a type 1 isolated gastric varix, treated with cyanoacrylate without complications ().
A scrotal US showed a large heterogeneous image in the left testicle area, with an echogenic and cystic solid component and flow presence with color Doppler assessment.
A contrasted CT scan of the thorax, abdomen, and pelvis showed a liver of normal size and density with multiple retrocrural, retroperitoneal, mesenteric, and left iliac metastatic lymphadenopathy which caused extrinsic compression of the portal vein along with splenic vein partial thrombosis with left-sided portal hypertension and perigastric and perisplenic collateral neovascularization (). A heterogeneous, well defined mass was found in the left testicle, 16.7 × 16.1 × 14.9 cm, with a solid component that was enhanced with the administration of contrast, as well as a cystic component. There was also invasion of the left spermatic cord.
The patient was extubated after surveillance and transferred to the Internal Medicine Department. We started chemotherapy with etoposide 100 mg/m2 and cisplatin 20 mg/m2, and seven days later the patient underwent a left radical orchiectomy by an inguinal approach with left hemiscrotectomy, without complications. Following this intervention, serum alpha-fetoprotein (AFP) level was reduced to 350 ng/mL, and the human chorionic gonadotropin level was 50 IU/mL.
A postoperative biopsy showed a pure testicular teratoma () with glandular formations and the presence of cartilage (a) and respiratory epithelium, with ciliated columnar cells alternating with goblet cells (b).
The patient was discharged after showing clinical improvement to receive ambulatory chemotherapy.


A 34-year-old female with a history of recurrent occipital seizures presented with a four-hour history of right visual field changes associated with left hemicranial headache. She described seeing a bright spinning beach ball in her right visual field intermittently, and physical exam showed constant right homonymous hemianopia. These symptoms were similar to those associated with a previous episode of clustered seizures that happened four years ago, at which point she was prescribed an antiepileptic agent, Levetiracetam. Continuous video EEG during the patient's most recent episodes showed left occipital sharp waves evolving into brief, frequent electrographic and clinical seizures, lasting 60–70 seconds ().
MRI with DWI, ADC, and T2/FLAIR showed diffusion restriction and hyperintense signal throughout the left occipital cortex (Figures , , and ). Given this appearance, the primary diagnostic consideration was an infarct. However, there was no significant mass effect on the ventricular system, and asymmetric increase in vessels seen on the left side on the postcontrast imaging suggested luxury perfusion. There was no mass-like enhancement or edema to suggest an infectious or neoplastic etiology. The patient was successfully discharged with resolving symptoms after an additional antiepileptic agent was introduced. Follow-up MRI performed six weeks later showed that the lesions involving the left occipital lobe completely resolved without any residual encephalomalacia ().
MRI scans that were obtained four years ago showed increase in diffuse cortical and FLAIR signal abnormality involving the left occipital lobe with more focal diffusion restriction and hyperintense T2 signal medially (Figures and ). EEG showed recurrent sharp wave activity along with focal slowing over the left occipital region, suggesting focal cortical irritability. Follow-up MRI five weeks later showed complete resolution (Figures , and ). She was placed on an antiepileptic medication at that time and had remained seizure-free for four years.


A 7-month-old Hispanic male was referred for nystagmus. He was born at term and exhibited normal growth but had motor and social developmental delay. Family history was significant for an older sister (Case 2) with visual abnormalities. His parents and two older brothers did not have any clinically significant visual problems. On examination, the patient fixed and followed with the left eye (OS) but not with the right eye (OD). Cycloplegic refraction (CR) was found to be −2.50 + 3.50 × 090° OD and −7.00 + 3.50 × 090° OS. Anterior segment examination was unremarkable for both eyes (OU). Funduscopic examination OD showed a tilted optic nerve with trace pallor and a large posterior RD involving the macula with surrounding demarcation lines and a subretinal fibrotic band (Fig. ). The remainder of the retina appeared thin and atrophic. No retinal tears or holes were identified. Fundus examination OS showed a tilted optic nerve, a tessellated retinal appearance, retinal pigment epithelium (RPE) mottling, and central macular atrophy. There was no evidence of a retinal tear or detachment.
B-scan ultrasound OD confirmed a posterior RD (Fig. ). Fluorescein angiography (FA) OD demonstrated early and late hyperfluorescence consistent with pooling (Fig. ). FA OS only demonstrated RPE window defects and staining of drusen-like deposits. A full field electroretinogram (ERG) was performed according to ISCEV standards with the 2009 LKC machine and a small, infant Burian-Allen contact lens electrode under general anesthesia. This ERG showed moderately to severely depressed responses from both the cone and rod systems. The depressed responses were greater than the ones that could be attributed to anesthesia, myopic refractive error or partial retinal detachment (Fig. ). Optical coherence tomography (OCT) of OD showed an elevated retina with subretinal fluid; OS revealed RPE changes and thinning. A hereditary retinal dystrophy panel, covering roughly 180 genes, was significant for a mutation in the CNGB3 gene associated with achromatopsia. This, however, was inconsistent with the clinical presentation. Subsequent whole exome and mitochondrial DNA sequencing demonstrated a homozygous mutation in the COL18A1 gene (NM_130445.3:c.2970_2971delAGinsC) associated with KS. Magnetic resonance imaging (MRI) of the brain demonstrated findings consistent with polymicrogyria but no evidence of an encephalocele (Fig. ). Fundus examination of the parents was unremarkable.


This 13-year-old female was the sibling of the 7-month-old boy from Case 1. She had a past ocular history significant for an ERG demonstrating mild cone-rod dystrophy, bilateral macular chorioretinal staphylomas, subnormal visual acuity, high myopia, and strabismus status post extraocular muscle surgery OU. Her medical history was significant for a history of precocious puberty at age 9. Her vision had been poor since birth but remained stable at 20/200 OU for the past 8 years. She was being reevaluated in light of her brother’s presentation. CR was found to be −9.00 + 0.50 × 110° OD and −11.50 + 2.00 × 080° OS with best-corrected visual acuity of 20/200 OU. On anterior segment exam there were bilateral patchy cortical cataracts. Fundus exam OU showed mild optic disc pallor, macular RPE atrophic changes, macular staphyloma, vascular attenuation, and a fundus with a tessellated appearance (Fig. ). Fundus autofluorescence confirmed significant RPE atrophic changes within the foveal and parafoveal regions of both eyes (Fig. ). OCT showed a mild staphyloma OD, moderate staphyloma OS, and irregular choriocapillaris with diffuse retinal thinning OU (Fig. ). A full field ERG was performed according to ISCEV standards using ESPION E3 system and DTL fiber recording electrodes. The ERG showed decreased amplitudes and delayed implicit times of the cone more than the rod system in both eyes. This ERG was consistent with cone-rod dystrophy that was stable compared to ERG obtained 4 years prior (Fig. ). Similar to her sibling from Case 1, the patient was found to have an identical homozygous mutation in the COL18A1 gene, and subsequent brain MRI showed findings consistent with polymicrogyria without evidence of an encephalocele (Fig. ).


A 38-year-old male with type 1 diabetes mellitus presented to our institute with severe substernal chest pain that started shortly after regaining consciousness from a short duration of hypoglycemic coma with documented blood glucose of 40 mg/dL. The patient had active chest pain upon presentation, and the electrocardiogram showed ST segment (isoelectric section of the electrocardiogram between the end of the S wave and the beginning of the T wave) elevations in the inferior leads with reciprocal changes (Figure ). An emergent left heart catheterization revealed an in-stent thrombosis in his previously placed nine-month-old stent despite being strictly compliant with a dual antiplatelet therapy including aspirin and ticagrelor (Figure ). Of interest, his first ST-elevation myocardial infarction nine months ago also was preceded by a hypoglycemic episode with documented low blood sugar levels, and he subsequently had a drug-eluting stent (DES) implanted in the right coronary artery. We had performed mechanical thrombus aspiration, and placed another DES distal to the previous stent (Figure ).


A 6-month-old male infant, previously healthy, was admitted for jaundice, tea colored urine and decreased oral intake with a history of ten days of afebrile upper respiratory tract infection for which he received clarithromycin for atypical organisms with dexamethasone Per Os syrup for symptomatic relief of cough. He has a negative history for familial hematologic diseases.
In the physical exam, there was marked pallor, icteric sclera with no hepatosplenomegaly and no pathological lymphadenopathies. He had normal blood pressure with a heart rate of 150 (mildly tachycardic for his age) and no tachypnea. Investigations revealed, on complete blood count (CBC), severe anemia with hemoglobin 4.5 g/dL (11–13 g/dL), MCV 120 fl (70–86 fl), platelets 80,000/mm3 (150,000–450,000/mm3) and high reticulocyte percentage (65%)(normal value < 1%). White count and differential were normal. The peripheral blood smear showed anisopoikilocytosis, macrocytosis, no hypochromia, polychromatophilia, numerous nucleated red blood cells, few spherocytes were present and schistocytes were absent. His biochemical studies showed increased indirect bilirubin (1.18 mg/dL) (normal value < 1mg/dL), decreased haptoglobin (0.02 g/L) (0.2–0.03 g/L), increased LDH (1323 U/L) (normal value < 280U/L), normal creatinine (0.23 mg/dL) (normal value < 1 mg/dL), normal folate and vitamin B12 levels. The immunohematological studies showed positive direct antiglobulin testing (DAT) using polyspecific antiglobulins (anti-IgG and anti-C3d) and positive DAT using the specific anti-IgG monoclonal antiglobulin. The indirect antiglobulin testing (IAT) was also positive and all cross matched blood units were incompatible. The titer of the autoantibody was very high (>1/40,960) with a strength of +4 and did not decrease until four months after the event. Immunoglobulins (IgG, IgM, and IgA) quantitation was normal. Antinuclear antibodies profile and rheumatic factor were also negative. Viral serology (Epstein-Barr virus, human immunodeficiency virus, hepatitis B and C viruses, adenoviruses.) was all normal except for CMV, which was positive—IgM titer was very high (nine times the upper limit) and the IgG titer was slightly above the upper limit. CMV PCR was also positive. The patient was managed medically without any packed red cell transfusion because he was relatively stable and constantly monitored. An intraveneous bolus of 4 mg/kg of methylprednisolone was given on day 0. A dose of 0.5 g/kg per day (half the required dose for financial reasons) of intraveneous immunoglobulins (IVIG) was given on day 1 plus a dose of 2 mg/kg per day of methylprednisolone that was continued alone for the next seven days before shifting to oral prednisone (2 mg/kg per day) for three weeks. Then, a progressive prednisone tapering over the next five months was planned. No specific CMV-immunoglobulins or antivirals were available. The hemoglobin level increased to 5.4 g/dL the second day, then progressively until 8.5 g/dL before discharge (time course of five days) and before shifting to oral prednisone. We lost sight of the patient as his parent did not bring him back for follow up until a month after stopping prednisone. He had a hemoglobin level of 11 g/dL and a platelet count of 230,000/mm3 at the time.


A 12-year-old girl 141 cm tall and weighing 26.4 kg presented with severe MG. The patient was healthy at birth, and in May 2013, she reported a history of persistent low-grade fever, blepharoptosis, weakness of the extremities, and dysarthrosis. In July 2013, seropositivity for anti-acetylcholine receptor (Ach-R) antibody, a positive Teng Shillong test, and surface electromyogram findings led to a diagnosis of whole-body MG. Despite the administration of immunoglobulin, difficulty in swallowing persisted and dyspnea progressed. At the end of July, she was intubated for mechanical ventilatory support and transferred to our institution. The initial ventilator settings were pressure-controlled, with a fractional inspired oxygen concentration of 0.35, respiratory rate of 10 breaths/min, inspiratory pressure (above positive end-expiratory pressure) of 10 cmH2O adjusted not to exceed a tidal volume of 10 ml/kg, and a positive end-expiratory pressure (PEEP) of 5 cmH2O. The PaO2/FiO2 ratio was > 300 mmHg, chest X-rays showed no abnormalities and signs of pneumonia. The patient was sedated with midazolam, fentanyl, and dexmedetomidine, but conscious and oriented (Richmond Agitation-Sedation Scale 0).
Respiratory muscle strength was evaluated every morning by MIP and diaphragm activity in relation to tidal volume (V
T/ΔE-di). E-di was measured with a size-appropriate multiple-array esophageal electrode (E-di catheter, 12 Fr, 125 cm) that was inserted using a method like that used to insert an ordinary nasogastric tube and positioned following the manufacturer’s recommendations. ΔE-di was calculated as the maximum minus the minimum E-di during inspiration []. Sedative drugs were discontinued at least 30 min before measuring MIP and V
T/ΔE-di, and the patient was fully conscious when the measurements were started. The measurements were stopped if at least one the following occurred. The blood oxygen saturation (SpO2) was < 90%, the respiratory rate was > 30/min, the systolic blood pressure was ≥ 180 mmHg, or cardiac arrhythmias developed. MIP was measured three times. The patient was encouraged to perform a maximal inspiratory effort with airway occlusion toward a closed circuit, and the largest test value was recorded. V
T/ΔE-di was measured with the same respirator settings, i.e., pressure support ventilation (PSV) mode, PEEP of 5 cmH2O, and pressure support of 5 cmH2O. V
T/ΔE-di was not obtained on day 6 for technical reasons. A few minutes after measuring MIP, the ventilator was set to PSV mode. After breathing was stabilized, airway pressure, flow, and E-di were recorded for 2 min. E-di measurements, acquired via the Servo-i ventilator, were transferred to a personal computer using Servo-i tracker software ® (Maquet, Critical Care AB, Sweden) for the entire duration of the study. Sedatives were restarted after completion of the measurements. On day 2 in the intensive care unit (ICU), the first of three large, consecutive daily doses of corticosteroid (methylprednisolone, 30 mg/kg/day) was given, and pyridostigmine bromide (1.1 mg/kg/day) was started on day 5. The patient’s clinical course is summarized in Fig. .
Figure shows the course of MIP. It increased slightly over time, but changed unpredictably day-by-day. MIP increased during high-dose corticosteroid therapy, but then suddenly decreased afterward. V
T/ΔE-di was measured by the same method every day (Fig. ). In contrast to the unpredictable time course of MIP, V
T/ΔE-di decreased consistently after day 4, which was the last day of corticosteroid pulse therapy. On day 7, the patient passed a spontaneous breathing trial (SBT) with PSV, 5 cmH2O PEEP and 5 cmH2O pressure support for 30 min. Taking her clinical symptoms into account, her diaphragmatic strength appeared to have recovered sufficiently, and she was extubated on that day. Hemodynamic instability, signs of respiratory muscle fatigue, dyspnea, airway obstruction, or decrease in arterial oxygen saturation were not observed following extubation. The patient was discharged from the ICU on day 9.


A 64-year-old female patient was admitted for moderate stuffy pain of the left chest for 6 months, and productive cough with fever in the recent half a month, without significant loss of weight. Her highest temperature during this period was 38.5°C. She was initially diagnosed as pneumonia in a community hospital, but the therapy using antibiotics of piperacillin-tazobactam for 1 week did not work. She had been working near a coal mine for more than 10 years, without history of hypertension or coronary heart disease. Her family and social histories were unremarkable. The patient underwent extensive radical resection of vulvar cutaneous MCC 10 years ago, and the surgical margin as well as inguinal lymph nodes were tumor-negative. She took cranial magnetic resonance, chest and abdomen computed tomography (CT) annually thereafter, which excluded tumor recurrence or metastasis in the past 9 years. Thorough physical examination failed to identify any suspicious lesions.
Related tests were carried out step by step for differential diagnosis. Laboratory tests for hepatic and renal functions were normal. Besides, repeated culture of her sputum for tuberculosis, fungus, parasite, or bacteria turned out to be negative. Diabetes mellitus and rheumatism were also excluded. Additionally, serum tumor markers of carcinoembryonic antigen, cytokeratin 19 fragment, squamous cell carcinoma, neuron specific enolase, alpha fetal protein, serum ferritin, β-human chorionic gonadotrophin (β-HCG), carbohydrate antigen 242 (CA242), CA72-4, CA153, CA125, and CA19-9 were all in normal range. Radiological examinations were performed, because her symptoms could not be explained by the above findings. Chest X-ray and CT revealed an irregular mass approximately 15.0 cm × 15.0 cm × 7.0 cm in size (Fig. A), which was located in the left thorax adjacent to the thoracic aorta. Atelectasis of left lower pulmonary lobe, enlarged mediastinal lymph nodes were also indicated (Fig. B). The cranial magnetic resonance image (MRI) and bone emission CT excluded detectable distant metastasis or other suspicious lesions. Positron emission tomography was not performed because it was not covered by her health insurance. CT-guided fine needle aspiration biopsy of the mass showed aggregation of atypical malignant cells (Fig. C). Further immunohistochemistry staining indicated positive expression of CD99, CD56, vimentin and Ki67 (20%), which indicated typical MCC. Thus, her diagnosis was corrected as locally advanced ectopic or single metastatic MCC with obstructive pneumonia, which could explain the complaints of chest pain and fever.
Radical surgery combined with adjuvant chemotherapy was assumed to be feasible after multidisciplinary consultation with specialists in medical oncology, gynaecology, and cardiothoracic surgery. The Eastern Cooperative Oncology Group Performance Status of the patient was grade 1. Preoperative tests of cardiopulmonary functions were carried out. Routine electrocardiogram, ultrasonic cardiogram indicated nothing abnormal. The forced expiratory volume in 1 second was 2.42 L, while the maximum voluntary ventilation was 73.4%. In addition, her left ventricular ejection fraction was 60%, which showed that this patient could tolerate thoracotomy. Preoperative surgical plan using three-dimensional (3D) printing model of this complicated tumor was not performed because of financial reason. The resection extent was decided to be along with the morphologically involved adjacent parietal pleura, pericardium, and diaphragm according to the principles of oncological surgery.
Antibiotics of cefatriaxone combined with levofloxacin were administered for 7 days before the surgery, and her temperature was reduced to 37°C. Then thoracotomy was performed through the 5th intercostal space, under general anesthesia and double-lumen endotracheal intubation. After the collapse of the left pulmonary lobes, fortunately, the significant distance between the tumor and thoracic aorta emerged. Meanwhile, adhesion of the mass with adjacent pericardium and pleura was observed during the surgery. Then a single-stage operation including left lower lobectomy, extensive resection of the mass, and mediastinal lymph node dissection was performed successfully, which took 290 minutes. Postoperative pathological staining of the mass revealed neuroendocrine carcinoma (Fig. D), which involved the left lower pulmonary lobe, adjacent pericardium, diaphragm, and pleura. The surgical margins and dissected lymph nodes were tumor-negative. In addition, the feeding vessels of the tumor were verified to be branches of internal thoracic vessels. Further immunohistochemical staining suggested positive expression of CD56 and Ki67 (25%), and negative chromogranin A, synaptophysin, CD10, P63, CK5/6, human leukocyte common antigen, vimentin and desmin, which revealed MCC.
Based on these findings, a diagnosis of intrathoracic ectopic, or single metastatic MCC (oligometastasis) was established, because her physical examination and pelvic CT did not indicate synchronous vulvar lesions. The patient was staged as IIB tentatively according to the 8th AJCC consensus guidelines for MCC (primary tumor invaded fascia, muscle, cartilage or bone, without regional lymph node metastases).[ However, it was not a definite diagnosis for insufficient histological evidence.
The postoperative recovery of the patient was mainly uneventful. Her body temperature returned to normal after the administration of piperacillin-tazobactam for another 7 days, and her chest pain was alleviated gradually. She was discharged 14 days after the surgery. Subsequently, she received 4 cycles of adjuvant chemotherapy with a mean interval of 21 days, using carboplatin (area under the curve [AUC] = 5) on day 1, and etoposide 100 mg daily on day 1 to 4. This patient survived without loco-regional recurrence or distant metastasis during the follow-up of 1 year.


A 32-year-old female, mother of two children, presented with persistent migraine-like headache, palpitations, progressive nausea and vomiting, photo- and sonophobia, menometrorrhagia and concomitant general fatigue. Clinical assessment changed markedly over the course of the following weeks whilst under exploration: she steadily became severely hypertensive, developed a distended abdomen and peripheral oedema, she gained nineteen kilograms in bodyweight. In addition acne, hyperpigmentation, and facial hair growth developed insidiously.
Further exploration revealed a severe hyponatremia (SIADH secondary to the use of carbamazepin for migraine) causing the headaches, photo- and sonophobia, nausea and vomiting as well as a severe hypokalemia explaining the palpitations and premature supraventricular complexes, ST-segment and T- wave abnormalities on ECG. As she started to show more pronounced systemic signs (hyperpigmentation, oedema, acne) laboratory tests revealed elevated cortisolemia levels (63.4 μg/dl; normal range: 6.2 - 18 μg/dl), abnormal 24 hours cortisoluria (7531 μg/24 hours; normal range: 3.5 - 45 μg/24 hours), increased ACTH level (846.1 ng/L; normal range: 10 - 60 ng/L) and an abnormal dexamethasone suppression test overnight. The diagnosis of Cushing’s syndrome was made. Urinary potassium levels of 19.39 mmol/L and a 24-hour kaliuresis of 80 mmol (normal range, 25 - 125 mmol/24h) were found, even while hypokalemia was severe. The transtubular potassium gradient was 12.7 (normal range <3), which indicated a mineralocorticoid effect. Following a negative MRI of the pituitary, the elevated plasma ACTH levels were indicative of ectopic production.
Initial therapy consisted of ketoconazole as suppression of cortisol production, together with one (empirical) gift of somatostatin, perindopril as antihypertensive drug, and low molecular weight heparins in preventive dosage for the elevated risk of thrombosis. In search of the ectopic ACTH production locus, CT scan revealed a voluminous pelvic tumour widely disseminated to liver and peritoneum with multiple retroperitoneal adenopathies (). Multiple sub-centimetrical pleural noduli were seen in the posterior upper right lung lobe.
A gynaecologic oncologist was consulted. Pelvic examination showed a hypertrophic cervix with pronounced smooth nodular aspect and multiple vaginal lesions with the same nodular appearance. The uterus was enlarged with multiple nodules presenting clinically as a 16 weeks pregnancy sized myomatous uterus with free parametria. An explorative diagnostic laparoscopy was performed. Internal inspection of the pelvis confirmed the presence of an enlarged, pale and nodular uterus whitish surrounded by multiple (>50) peritoneal implants with similar appearance. Implants were also noted in the omentum and at the right diaphragm with moderate ascites. The ovaries were normal. Biopsies of the cervix and two peritoneal implants were taken, revealing a high-grade neuroendocrine carcinoma in both the peritoneal implants and cervix (though subepithelial location in the cervix). This conclusion was based on histomorphological features (trabecular proliferation of monotonous population of small cells with hyperchromatic nuclei and moulding; high mitotic and apoptotic activity) combined with positive neuroendocrine markers such as CD56/NCAM (neural cell adhesion molecule) (), synaptophysine, chromogranine (with positive external control) and positive cytoplasmic dot-like pankeratin staining. The final diagnosis of FIGO stage IVb endometrial carcinoma was made.
Serum tumour markers neuron-specific enolase (NSE) and chromogranin were positive respectively 285 ng/ml (normal range <15 ng/ mL) and 544 μg/L (normal range <36.4 μg/L). Palliative chemotherapy with a combination of cisplatin and etoposide was proposed. Prior to the first administration of chemotherapy the patient developed erysipelas of the right leg. Intravenous anti- biotics were administered and chemotherapy was started. The next day her condition worsened with persistent fever and a rising CRP. She developed a septic shock and in spite of antibiotherapy and maximal supportive therapy she died 48 hours after the initiation of chemotherapy.


A 43-year-old man was admitted to our hospital for acute postprandial abdominal pain, nausea and vomiting, without dyspnea and myasthenia. There was no history of trauma. Physical examination found that trachea shifted to the right, breathing sound over the left lower chest decreased, cardiac border shifted to the right and tenderness in the upper abdomen. A chest X-ray showed that mediastinum and trachea shifted to the right and the left diaphragm lifted. Upper digestive tract radiograph (Fig. ) showed left diaphragm elevated, gastric fundus and body lifted with nearly vertical gastroesophageal angle. A diagnosis of organoaxial gastric volvulus was suspected. On CT scan (Fig. ), an irregular mass was found in the anterior mediastinum, about 6.8 × 9.5 cm, left diaphragm was elevated, stomach, spleen, parts of bowels were lifted. Emergency gastroscopy (Fig. ) demonstrated gastric body volvulus. He was treated with endoscopic de-rotation.
The ultrasound guided biopsy of mediastinal mass was performed for this patient. The pathological findings revealed type B3 thymoma. According to the imaging examination he was diagnosed as Masaoka stage III thymoma. The thymoma of this patient presented with extensive pericardium, aorta arch and its branch infiltration, so it was considered as unresectable disease.
The patient with technically unresectable disease received radiotherapy from December 2013. Gastric volvulus still attacked about once a month, with the incentives of cold, satiety or spicy food. Each time endoscopic de-rotation was needed to relieve the symptoms. In 10 months later, CT scan showed the mass in the anterior mediastinum shrank, but a new small lesion developed on the left pleura. CT-guided biopsy of the pleural mass was performed. The histopathology and immunohistochemistry proved thymoma metastasis. The chemotherapy of carboplatin combined with paclitaxel was given for four cycles. He also received radiotherapy on the pleural mass. Disease was stable for 7 months. Gastric volvulus still occurred with less frequency of about every three to four months, and the symptoms were less severe. The left pleural effusion developed in May 2015. The disease was evaluated as progression. Then he received the chemotherapy of ADOC regimen (cisplatin, doxorubicin, vincristine, cyclophosphamide) for 2 cycles. Till March 2017, he was still alive with slow progression. The gastric volvulus still occurred every 3–4 months.