A 42-year-old man was referred to our hospital for treatment of a necrotizing pancreatitis. He had no history of medication or alcohol consumption. Laboratory studies revealed white blood cell count 20,200/mm3, hemoglobin 17.4 g/dL, platelet count 25,8000/mm3, serum total bilirubin 2.17 mg/dL, AST 266 U/L, ALT 196 U/L, amylase 1670 U/L, and lipase 2673 U/L. An abdominal CT scan showed acute necrotizing pancreatitis with large amount of peripancreatic necrotic fluid collections (). He was admitted to the intensive care unit (ICU) and protease inhibitor and empirical antibiotics treatment was initiated. He presented a cardiac arrest requiring cardiopulmonary resuscitation for 20 minutes, and continuous renal replacement therapy (CRRT) and mechanical ventilation were needed for combined multiorgan failure. An abdominal CT scan following 4 weeks of medical treatment in ICU demonstrated a huge pseudocyst (). Despite endoscopic transgastric internal drainage and percutaneous drainage, fever and abdominal pain were not subsided. A follow-up abdominal CT scan after 8 weeks from admission revealed the decreased but still remaining large amount of necrotic collections () and SVT with engorgement of perigastric veins (). An emergency operation for necrosectomy and external drainage was performed. On operative field, severe adhesion and bleeding tendency was noted. On postoperative day 13, hematemesis occurred. Blood pressure was 90/60 mmHg and hemoglobin decreased from 11.2 g/dL to 7.6 g/dL. An abdominal CT scan revealed extravasation of contrast media at gastric cardia and fundus (). After initial resuscitation, an emergency esophagogastroduodenoscopy (EGD) was performed. It showed a huge clot in the stomach, and active bleeding from gastric fundus was suspected. However, the focus of bleeding could not be identified exactly due to the presence of large clot and ongoing active bleeding (). He was referred to intervention unit and underwent an emergency angiography. Celiac and splenic arteriography revealed no active bleeding from arterial system (Figures -). Under suspicion of bleeding GVs, SAE was performed using vascular plug (). The vascular plug was placed at distal splenic artery just proximal to branching in splenic hilum. After SAE, splenic flow was remarkably decreased (). During the procedure, his systolic blood pressure was 70~80 mmHg and heart rate was 140~150 beats per minute. Four packs of PRCs were transfused after SAE. After the procedure, bleeding stopped immediately, and no more episode of gastrointestinal bleeding was observed. An abdominal CT scan 2 days following the SAE showed no more bleeding. A small splenic infarction was seen, but the infarcted volume was less than 10% of total splenic volume (). Any treatment for splenic infarction was not needed. At present, 4 months following the SAE, no more episode of variceal bleeding was observed and no infarcted area of spleen was seen on a follow-up abdominal CT scan ().


A 72-year-old male presented to our hospital with symptoms of an acute headache and slurred speech. His past medical history included hypertension, hypothyroidism, and a recent diagnosis of left superficial femoral and popliteal vein thrombosis. He was known to our hematology/oncology service for a diagnosis of blastic plasmacytoid dendritic cell neoplasm treated with chemotherapy and allogeneic stem cell transplant (day 137 at presentation). He was on rivaroxaban for the deep vein thrombosis (DVT), tacrolimus for graft-versus-host disease (GVHD) prophylaxis as well as standard post-transplant antimicrobial prophylaxis. On examination, he had decreased strength in his bilateral lower extremities with a power of 4/5. The rest of the examination was unremarkable. He was an ex-smoker with social alcohol use. The laboratory findings were consistent with pancytopenia at his baseline and a therapeutic tacrolimus level.
The patient’s neurologic symptoms prompted an MRI of the brain that revealed two ring-enhancing lesions: a 1.6 cm lesion in the right frontal lobe and a 1 cm lesion in the left parietal lobe, both with surrounding vasogenic edema (Figure ). A review of the patient’s records revealed that he had a CT chest scan a month prior to presentation for follow-up of a pulmonary nodule that showed a new 1.4 cm solid right upper lobe nodule. This was followed by bronchoscopy and bronchoalveolar fluid examination that was negative for gram stain, fungal, pneumocystis and acid-fast stains and cultures. Clusters of acute inflammatory cells were seen; no malignant cells were present. The patient’s inpatient CT chest scan revealed enlargement of the previous nodule, now measuring 3.3 x 2.5 x 2.1 cm, prompting a CT-guided fine-needle aspiration biopsy (Figure ). The pathology was consistent with inflammatory changes including abscess formation and focal necrosis. The specimen was sent for bacterial, fungal, and mycobacterial cultures and cytology. Meanwhile, the patient also had a lumbar puncture with cerebrospinal fluid (CSF) analysis that failed to reveal any abnormality. The CSF culture did not show any growth. Serology for toxoplasma, histoplasma, coccidioides and cryptococcus was negative. The patient was started on empiric therapy with intravenous TMP-SMX and liposomal amphotericin B along with dexamethasone for vasogenic brain edema. The tissue mycology culture was reported positive for nocardia species. The acid-fast stain was negative, and the acid-fast culture was also positive for nocardia species. The patient was discharged on intravenous TMP-SMX with a peripherally inserted central catheter (PICC) in place.
A follow-up CT chest scan and MRI brain scan four months later showed resolution of the right upper lobe nodule with residual scarring and decrease in size of the ring-enhancing brain lesions: right frontal lobe lesion 7 mm down from 1.6 cm and left parietal lobe lesion 8 mm down from 1 cm. The patient will continue TMP-SMX for a total of nine to 12 months.


A 33-year-old male was admitted for abdominal distention after meals. He had a history of surgery for hydatid liver cyst two years ago at another center. The 14x10 cm in size cyst was located at the hilum of the liver and there was portal venous thrombosis and cavernous transformation at hepatic hilum. The cyst had been treated with partial cystectomy, omentoplasty, and postoperative adjuvant albendazole (800mg per day). Two weeks after the surgery, a percutaneous drainage had been performed due to ongoing postoperative abdominal pain. After percutaneous drainage, a biliary fistula appeared and was treated with endoscopic retrograde cholangiography. At the admission to our center, his laboratory tests were in normal ranges. Abdominal imaging methods (ultrasound, computed tomography and magnetic resonance imaging) revealed splenomegaly, portal vein thrombosis, and cavernous transformation at hepatic hilum and the previously treated hydatid cyst ().
Upper gastrointestinal endoscopy demonstrated the esophageal and gastric fundal varices. Due to his young age and low risk for surgery, the patient was planned for a meso-caval shunt and hydatid liver cyst surgery. At laparotomy, hydatid liver cyst was obliterated with omentum. There was no sign of active viable hydatid disease. An 8 mm cryopreserved iliac vein graft was placed between the vena cava and the superior mesenteric vein ().
Cholecystectomy was also added for the prevention of the potential future surgeries at the hepatic hilum. Postoperative period was smooth except an intraabdominal oozing due to anticoagulant therapy. It was conservatively treated and the patient was discharged on day 10. The postoperative imaging evaluation showed the patent meso-caval shunt (). In the postoperative period, his symptoms and endoscopic varices were regressed.


Our case is a 4 years and 8-month-old Syrian Arabic girl with a birth weight of 4 kg, who is the sixth of seven siblings born to healthy consanguineous parents. She followed normal psychomotor development and experienced no remarkable illness until the age of 4 years and 2 months when her parents noticed a rapid weight gain (about 1 kg every 10 to 15 days) due to excessive eating (she required six to seven big meals/day). Later, they observed her to have alterations in body secretion (decreased tears when crying, decreased nasal discharge, unfavorable body odor, and decreased sweating) in addition to blue cold extremities, diarrhea alternated with constipation, polyuria, and polydipsia. Two months after the onset of obesity she had urinary incontinence during night sleep. Then, significant behavioral changes developed including: mood alteration, anxiety episodes, rage attacks, nervousness, and aggressive behavior, in addition to recurrent fatigue, social withdrawal, prolonged periods of sleep (12 hours continuously), and difficulty staying awake during the day. These complaints grew to be a serious concern to the family so she was admitted to Damascus Children Hospital, endocrinal department, at the age of 4.5 years, for further investigations.
For three generations, the family history was negative for similar presentations, obesity, or psychiatric disorders. It was noteworthy that an older sister of our patient had died at the age of 12 years with a diagnosis of acute myeloid leukemia (AML). Her sister’s malignancy was not accompanied by any of the signs or symptoms our patient had.
On physical examination, general obesity was noticed without striae or altered skin pigmentation. No dysmorphic features were observed, neither were there any minor or major congenital malformations. Her weight was 25 kg (above 97% percentile) while her length and head circumference measured 110 cm (at 90% percentile) and 52 cm respectively. Her body mass index (BMI) was equal to 20.1 (Figs. and ).
An ophthalmic examination revealed left exotropia with normal fundus and normal papillary response. The performed laboratory analyses did not indicate any significant abnormality. Her complete blood count (CBC), blood glucose, sodium (Na), chlorine (Cl), potassium (K), calcium (Ca), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), cholesterol, urine density, creatinine, and urea were all within normal limits. Her thyroid-stimulating hormone (TSH), free thyroxine (T4), morning cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), insulin-like growth factor-1 (IGF1), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also within normal limits.
Her abdominal and pelvic ultrasound was normal. Her bone age was slightly advanced and it fitted 5 to 5.5 years old. Brain magnetic resonance imaging (MRI) was normal; it showed no cortical atrophy. A homogenous mild enlargement of her pituitary gland was observed on both T1-weighted and T2-weighted images with normal hyperintense posterior lobe on T1-weighted images (Figs. and ).
Since the endocrine function tests were normal, her symptoms had been explained on the basis of psychotropic origin, and she was discharged with antipsychotic medication (risperidone 1 mg orally per day) and the recommendation to follow up at the out-patient psychiatric clinic after 3 months of prescribed treatment. After 3 months of discharge, when she was 4 years and 8 months old, she developed dyspnea that worsened with exertion and during sleep, continuous snoring, and recurrent chest pain. The respiratory symptoms lasted for 5 days after which she had two episodes of cyanosis and obstructive apnea which lasted for 10 minutes with improvement via oxygen mask. As a result of progressive respiratory distress (respiratory rate 35/min, expiratory grunting, flaring of nostrils, wheezing with prolonged expiration, and remarkably loud snoring) she was readmitted to Damascus Children Hospital, intensive care unit (ICU). Investigations showed hypoxemia, hypercapnia, and respiratory acidosis accompanied by radiological evidence of a big round opacity in her right lung (Fig. ).
She was intubated 24 hours after admission and attached to a mechanical ventilator because of severe respiratory distress with altered consciousness: blood gases were pH 7.27, partial pressure of carbon dioxide (PaCO2) 79 mmHg, partial pressure of oxygen (PaO2) 38 mmHg, and oxygen saturation 79%. Her laboratory results were within normal limits except for elevated values of Na (up to 162) and C-reactive protein (77 mg/L). During this admission, her weight was recorded as 40 kg (>97th percentile).
A chest computed tomography (CT) scan demonstrated a 6 cm round mass filling most of her right lung and pushing her heart and mediastinum to the left with infiltration and consolidation of the right lower lobe of her right lung (Fig. ).
Subsequently, when her health stabilized, a complete resection was performed of a 10×10 cm solid round mass from the posterior wall of her chest. It was a mature ganglioneuroma (Fig. ).
Her unexplained rapid gain of weight and the presence of chest ganglioneuroma brought attention to ROHAAD syndrome as a diagnosis of her situation and helped to exclude other illnesses that could be considered in the differential diagnosis. Familial obesity and Prader–Willi syndrome were both excluded since her family history did not support the first, and with the absence of mental retardation and congenital abnormalities there was no indication to investigate the latter.
A good improvement in consciousness was achieved by stopping sedative drugs, so she was able to speak, move her limbs, and interact with others. Nevertheless, she required prolonged ventilation because of respiratory instability and she had myoclonic seizures. Three attempts at extubation failed without a clear reason. A brain MRI was ordered which revealed a generalized cortical atrophy of her brain with the same mild pituitary gland enlargement observed in a previous MRI (Fig. ).
A month after her admission to the ICU, a tracheostomy was performed because of lack of spontaneous breathing. One week later, she had cardiorespiratory arrest and died. A timeline of her signs and symptoms is shown in Fig. .


A 40-year-old lady presented with history of a reddish painless swelling in the left forearm since 3 months, gradually increasing in size. During the following days, she developed multiple nodular swellings all over the body. There was no fever or weight loss. She presented to us following a biopsy from the forearm swelling.
On examination, her general condition was good. She had multiple erythematous papular lesions and nodular swellings of 1–3 cm over both legs, both arms, chest wall, abdomen, back, face, scalp, and ear lobules (Figures , , and ). She also had bilateral supraclavicular and left cervical lymphadenopathy of 1 cm. There was no organomegaly.
Her hemoglobin was 116 gm/L, total WBC count was 9.7 × 109/L, platelet count was 236 × 109/L, and the peripheral smear showed 42% blast cells. Her renal and liver functions were normal, and serum lactate dehydrogenase was 2327 U/L. Section from the skin biopsy showed diffusely arranged atypical cells, which were positive for LCA and negative for CD20 on immunohistochemistry (). A bone marrow aspiration showed sheets of immature cells with blue vacuolated cytoplasm, round nuclei, and 1-2 nucleoli (). The abnormal cells were positive for periodic acid schiff (PAS) and nonspecific esterase (NSE) and negative for peroxidase by cytochemistry. Immunophenotyping by flow cytometry showed the abnormal cells to be positive for the myeloid markers CD33 and CD11c and negative for the myeloid markers CD13, CD14, CD61, CD64, CD117, anti-MPO, and cyCD61. The cells were also positive for the T-cell markers cyCD3, CD4, CD5, and CD7 and negative for the T-cell markers CD3, CD8, CD56, anti-Tdt, TCrgd, TCrab, and CD1a. The cells were negative for all B-cell markers CD10, CD19, CD20, and cyCD79a. A diagnosis of mixed phenotypic acute leukemia of T/myeloid with monocytic differentiation lineage was made. The skin lesions showed good response to steroids. She was started on chemotherapy with Hyper-CVAD protocol, her skin lesions completely disappeared during the first cycle of chemotherapy, and she achieved complete bone marrow remission with <3% blasts after the first cycle. She has completed 2A cycle and continues to be in remission.


An 80-year-old man presented to our hospital with anorexia and jaundice that had been present for several weeks. The patient had neither abdominal tenderness nor a palpable mass in the right upper quadrant of the abdomen. He underwent endoscopic submucosal dissection for multiple early gastric cancers 1 year ago, and all of the lesions were resected radically. He had severe chronic obstructive pulmonary disease because of long-term smoking. The patient’s main occupation was in agriculture, and he had never worked in the printing or staining industries. The patient had no family history of cancer.
On the day of admission, his complete blood count and serum biochemical parameters were as follows: white blood cells, 10.5 × 103/μL (normal range 3.3–9.0 × 103/μL); red blood cells, 28.5 × 106/μL (4.3–5.7 × 106/μL); hemoglobin, 9.2 g/dL (13.5–17.5 g/dL); total protein, 5.0 g/dL (6.7–8.3 g/dL); albumin, 1.5 g/dL (4.0–5.0 g/dL); total bilirubin, 26.0 mg/dL (0.3–1.1 mg/dL); direct bilirubin, 17.0 mg/dL (0.1–0.5 mg/dL); aspartate aminotransaminase, 91 IU/L (normal 10–40 IU/L); alanine aminophosphatase, 90 IU/L (5–45 IU/L); aspartate transferase, 1560 IU/L (100–325 IU/L); and gamma-glutamyltranspeptidase, 278 IU/L (7–80 IU/L). His carbohydrate antigen 19-9 (CA19-9) was 40,635 U/mL (0–37 U/mL), and carcinoembryonic antigen (CEA) was 10.4 ng/mL (0–5.0 ng/mL). Alpha fetoprotein levels were within normal limits.
An abdominal computed tomography (CT) scan revealed an enhanced mass that was approximately 2.5 cm in size located in the mid common bile duct (CBD) and an enlarged regional node in the hepatoduodenal ligament (Fig. a). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed high accumulation of FDG with a maximum standardized uptake value (SUVmax) of 20.7 by the CBD tumor (Fig. b).
Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated severe intrahepatic bile duct dilatation and a filling defect in the mid-CBD. The tumor was involved with the cystic duct. After the ERCP, endoscopic placement of a nasobiliary biliary drainage catheter was performed (Fig. ). The bile and brush cytology performed at the same time revealed a few degenerative atypical cells (class 3).
The patient underwent surgery with the presumed diagnosis of bile duct cancer. The operative method was extrahepatic bile duct resection with lymph node dissection and reconstruction with a Roux en Y hepaticojejunostomy because of his advanced age and severe pulmonary emphysema. The 18 regional lymph nodes were resected. The right hepatic artery was fixed to the tumor, and we performed a complicated resection. There was evidence of local cancer invasion, but no signs of distant metastasis or organ invasion were noted. The resection margins of the proximal and distal bile duct frozen biopsy were tumor free. Peritoneal lavage cytology during the operation was negative.
Macroscopically, the surgical specimen showed a light gray invasive nodular tumor measuring 2.4 × 1.9 cm located in the mid-CBD (Fig. a). The sectioned surface of the resected specimen showed tumor invasion beyond the bile duct serosa (Fig. b). There were no gallstones in either the gallbladder or bile ducts.
On histopathological examination of the resected specimen stained with hematoxylin and eosin, the tumor was structured with two components (Fig. a). There was no transitional area between the two components. High cellularity components made up approximately 90% of the tumor and exhibited invasion throughout the entire CBD wall with serosal penetration (Fig. b). The other component was tubular adenocarcinoma, and it occupied a small area of the tumor in the superficial mucosal portion (Fig. c). In the LCNEC area, the tumor was solid and cellular with necrosis inside. There was no differentiation into duct structures. The tumor cells were joined together, and the cells, nucleus, and cytoplasm were relatively large (Fig. d). A high-power image of d shows that the tumor cells were large idioblasts and the nucleolus was clear. Each nucleus variant was strong, and the heteromorphic nuclei division image was obvious (Fig. e).
Immunohistochemical findings in the LCNEC component indicated that the tumor cells were immunopositive for neuroendocrine markers, including synaptophysin and CD56, but were negative for chromogranin A and neurospecific enolase (NSE) (Fig. a–c). Immunostaining for Ki-67 showed a strong positive of 72% (Fig. d). Immunohistochemical findings in the adenocarcinoma component indicated that the tumor cells were not immunopositive for neuroendocrine markers (Fig. a–c). There were no transitional areas between the components. Staining for Ki-67 showed mild positive at 27% (Fig. d). Metastases from the LCNEC were noted in two of the 18 lymph nodes. The metastatic lymph nodes were in contact with the tumor.
No postoperative complications occurred, and the patient was discharged. His CEA and CA19-9 levels normalized after the operation.
The patient had peritoneal metastases develop during the early postoperative period, and a postoperative CT only 2.5 months later showed a lung metastasis and multiple liver metastases occupying half of the liver. The patient died 3 months after surgery.
In the World Health Organization classification, neuroendocrine neoplasms are classified into five general categories, including neuroendocrine tumor (NET), NEC, mixed adenoneuroendocrine carcinoma (MANEC), goblet cell carcinoid, and tubular carcinoid. In addition, NECs are classified as either LCNEC or small-cell neuroendocrine carcinoma (SCNEC) []. When each component is more than 30% of the tumor, it is defined as MANEC.
The bile ducts are one of the rarest primary organs for NET, accounting for only 0.2 to 2.0% of all such tumors []. NEC arising in the extrahepatic bile duct includes pure NEC, MANEC, and NEC with adenocarcinoma, but only 27 cases have been described previously in the literature [–] (Table ). Of these, 19 cases were pure NEC and eight cases were composite glandular–endocrine cell carcinoma of the extrahepatic bile ducts. Most of these cases (82%) were SCNEC, and LCNEC was extremely rare, only five cases. Sato et al. first reported LCNEC with adenocarcinoma in the CBD in 2006 [], and thus, our case becomes the sixth report of LCNEC arising in the extrahepatic bile duct.
Sasatomi (2013), Ninomiya (2013), and Park (2014) reported cases of pure LCNEC in the CBD [–]. From what can be analyzed from the literature, the mean tumor diameter was 3.5 cm (range 0.3–6.5 cm), median survival time was 12.0 months (range 0.7–45 m), and the 1-year survival rate was 32.6%. In 84% of cases, radical resection was performed.
The pathological fact that normal bile duct mucosa does not have neuroendocrine cells was cited as one of the reasons why a primary NEC of the CBD is extremely rare. Harada et al. examined 274 cases of biliary cancer and reported that MANET was found in 4% of hepatic hilar cholangiocarcinomas with hepatolithiasis, 10% of gallbladder cancers, and 4% of extrahepatic cholangiocarcinomas []. The authors of this report expressed the opinion that normal adenocarcinoma developed during a process of growth and dedifferentiation to endocrine cells. Albores et al. reported that neuroendocrine cells could be detected at sites of intestinal metaplasia induced by chronic inflammation due to cholelithiasis and congenital anomalies, which might be the initial step in the development of neuroendocrine tumors of the CBD []. The process suggested this report was one reason why pure NET and NEC developed. Although pure NET cases without dysplastic intestinal-type epithelium exist, they seem to follow a different developmental process.
LCNEC of the CBD is a poorly differentiated and rare tumor that exhibits high-grade NET with aggressive behavior and has a strong tendency to develop early lymph node and distant metastases. The survival duration of previously reported cases of LCNEC of the CBD ranged from only 21 days to 12 months after surgery (Table ). In our case, the recurrence was noted 2.5 months after surgery, and the patient died 3 weeks after the recurrence. The prognosis of LCNEC is extremely poor in comparison with adenocarcinoma of the same clinical stage, even if we can resect the tumor radically.
In this case, we chose to perform extrahepatic bile duct resection, which is not commonly used. In cases of extrahepatic bile duct cancer with obstruction of the cystic duct, we usually perform subtotal stomach-preserving pancreatoduodenectomy because of metastasis of lymph nodes around the head of the pancreas and direct invasion to the pancreatic parenchyma. Because the patient was 80 years old and had progressive dementia and severe pulmonary emphysema, once the resection margin of the distal CBD frozen biopsy was tumor free, with the consent of his family, we decided to defer pancreatoduodenectomy. We do not believe that this reduction surgery caused early postoperative liver metastasis.
Adjuvant chemotherapy in three cases of LCNEC of the CBD was reported previously [, , ], and these patients survived 3 to 12 months. Yamaguchi et al. reported that adjuvant chemotherapy with gemcitabine could not suppress the recurrence, but hepatic artery infusion with CPT-11 (40 mg/kg body weight) and CDDP (20 mg/kg body weight) every 2 weeks remarkably decreased tumor markers and the size of both lymph nodes and liver tumors [].
At present, it is controversial whether a combination of chemotherapy and radiotherapy is more effective than resection alone [, ]. In this case, we could not provide adjuvant chemotherapy because of the general poor condition of the patient. Because peritoneal, lung, and liver metastases developed during the early postoperative period, it was hard to attempt any adjuvant chemotherapy in LCNEC. If a diagnosis of LCNEC of the CBD was possible preoperatively, we could consider neoadjuvant multimodal treatments before resection to improve the prognosis [, , ]. However, it was difficult to diagnose NEC of the CBD preoperatively, because there is no difference between adenocarcinoma and NEC in symptoms, blood tests, and imaging studies. In most cases, the definitive diagnosis was established by histopathological and immunohistochemical analysis of the surgical specimen. Only three cases were diagnosed preoperatively by percutaneous transhepatic cholangioscopy with biopsy [], ERCP with brushing [], and endoscopic ultrasonography-guided fine-needle aspiration biopsy []. In our case, we were not able to detect malignant cells by brush cytology of the bile duct. The submucosal location of NEC causes a large number of false-negative results on brush biopsy, making it difficult to achieve a correct preoperative diagnosis.
In our case, CA19-9 was elevated to a high level (40,635 U/mL), but it was thought that the abnormal value was caused by chronic cholestasis and cholangitis. The patient’s postoperative values of CA19-9 reduced to a normal level immediately and did not correlate with the cancer recurrence.
Cho et al. suggested that NEC of the CBD should be considered in differential diagnosis of causes of obstructive jaundice and hemobilia []. We examined the intraductal ultrasonography of the CBD in our case and detected a large quantity of clots in the lower bile duct. It was thought that this appearance was due to LCNEC, which was often associated with necrosis. The Ki-67 index in the LCNEC component was higher than in the adenocarcinoma component (72 vs. 27%), and probably reflecting this difference, the SUVmax of the LCNEC was high (20.7) on the FDG-PET. When the SUVmax reaches an abnormally high level, it seems reasonable to suspect a different type of carcinoma.


A seventeen-year-old African American male was taking nitrous oxide under high pressure via balloon inhalation at the time of a music festival and also two days prior to the event. He admitted to inhaling approximately fifty balloons worth of gas in total. He had also taken one MDMA (ecstasy) tablet. He noted swelling of the neck with pain and discomfort and presented to the accident and emergency department of the local hospital. The patient denied dysphonia, shortness of breath, and chest pain. On examination his observations were stable. He was saturating at 98% on 2 litres of oxygen. There was marked bilateral neck swelling, extending to the right chest wall and his entire right arm down to his wrist. There was easily palpable crepitus of the aforementioned areas. The airway was central and patent, chest was clear, and there was equal bilateral air entry as well as normal chest wall expansion. Heart sounds were also normal.
A chest X-ray demonstrated extensive pneumomediastinum of the chest wall and neck, affecting the anterior chest wall, and subcutaneous emphysema can outline the pectoralis major muscle, giving rise to the ginkgo leaf sign ().
A CT scan () with intravenous contrast confirmed pneumomediastinum and surgical emphysema. The cause of it could not be identified, but there was no obvious tracheal injury or oesophageal rupture apparent. Subcutaneous emphysema is readily visible on CT scans, with pockets of air seen as extremely dark low (air) attenuation areas in the subcutaneous space.
The patient was admitted for observation in case of clinical deterioration and potential infection. Although he remained stable and well in himself, the considerable pneumomediastinum seen on initial imaging, combined with concern that this young otherwise healthy patient might be compensating and hence masking a more serious underlying condition, in particular, oesophageal perforation, led to a water soluble (gastrografin) swallow being requested. This revealed no leak of contrast outside the gastrointestinal tract. Given the recent history, a diagnosis of barotrauma with subsequent pneumomediastinum secondary to nitrous oxide inhalation was established.
The patient was discharged home under care of his parents three days after admission. He was strongly advised against future use of the gas for recreational purposes and was told to avoid any contact sports for a duration of six weeks. His subcutaneous emphysema got much better at day 3 on discharge. At 2-week clinic follow-up, it had completely resolved.


Five-year-old male patient was admitted to our clinic with complaint of swelling in the left side of the neck, which was not accompanied by any pain for four months. He had no other complaints like loss of weight, fever, night sweating, respiratory distress, or difficulty swallowing. In the physical examination, a hard, mobile mass with an approximate size of 2∗3 cm was detected on the front of musculus sternocleidomastoideus in patient's neck. A neck ultrasonography, which had been conducted in the external center, had the result of a lymphadenopathy with the size of 28∗21 mm and with no fat hilus on musculus sternocleidomastoideus anterior.
Magnetic resonance imaging of the neck showed a properly limited lesion with 2,8∗2,3 cm size on the front of musculus sternocleidomastoideus and internal carotid artery. The lesion which pushes parotid gland towards the front was starting from the inferior part of the posterior digastric muscle and progressing up to the C4 level ().
A fine-needle aspiration biopsy was offered but refused by the family. In his examination 1 month later, the mass in the neck was found to be approximately 4∗4 cm. Patient's family was informed that the mass to be extracted by surgery is deep under large arteries in the neck, that it may cover nerves outside the lymph node, and that there are risks of possible lowering of the left eyelid and in operation of the left vocal cord. The family gave written consent for the surgery. The patient underwent the operation with provisional diagnosis of lymphadenopathy and a tumor of nerve origin.
The properly limited and encapsulated mass on musculus sternocleidomastoideus, which was pushing the carotid artery and internal jugular vein into lateral position, was separated from surrounding tissue by blunt dissection. It was observed that the mass had nerve continuity in its upper and lower regions and it was in fact of nerve origin. Nerves in the upper part were connected by clamping and the nerves which were severed during blunt dissection were made into another specimen. The total mass was extracted ().
Pathological diagnosis was reported as intermixed type ganglioneuroblastoma. While there was no calcification on the encapsulated tumor which was rich in terms of stroma Schwann cells, it was found that ganglioneuromatosis component is over 50%. In addition, differentiation neuroblasts and immature and dysplastic ganglion cells were observed under microscopic examination ().
Patient had developed ipsilateral Horner syndrome (miosis, ptosis, and anhidrosis) in the postoperative period. However, no sign of this was found in the 3rd-month control examination. Tests like abdominal and thorax imaging, complete blood count, bone marrow aspiration test, 24-hour urinary VMA, and N-myc protooncogene protein scan were conducted. No pathological findings were observed. After the I-131 Metaiodobenzylguanidine (I-131 MIBG) scan in the 6th-month control examination, an involvement was observed in the right cervical region, the opposite area of the operated region, and patient was directed to adjuvant chemotherapy. No evidence of any recurrence was found in the 12th-month control examination.


A 35-year-old woman presented to her primary care with one-month history of new-onset abdominal pain and hematemesis. Her medical condition was otherwise significant for hypertension, diabetes mellitus type II, and fatty liver disease. She did not have a significant surgical history.
On abdominal computed tomography (CT), the patient was found to have gastrohepatic lymphadenopathy, a feature not present on the most recent imaging report from 2 years priorly, suggestive of a possible gastric malignancy. There was otherwise no abnormality detected on CT. Further work-up included an endoscopy which showed a 1.8 cm polyp in the fundus of stomach.
A polypectomy was performed; the fragments ranged from 0.6 to 1.4 cm in the greatest dimensions. Microscopically, there was WD-NET (intermediate grade, G2) extending to the tissue edges. The background mucosa was negative for autoimmune gastritis and was otherwise unremarkable.
The patient was scheduled for gastric resection. At the time of surgery, enlargement of gastric lymph nodes was noted. The gastrectomy specimen measured 32 cm along the greater curvature and 15 cm along the lesser curvature and ranged from 2.5 to 10 cm in the diameter (). In the fundic region, there was an irregular mucosal defect associated with underlying tattoo, consistent with prior biopsy site (). Otherwise, there was no gastric mass or other lesion. Gastric lymph nodes were enlarged and readily identifiable. En bloc sampling to include the region of mucosal defect and the entire unremarkable surrounding tissue was performed.
Microscopically, a single 3 mm focus of residual neuroendocrine tumor was present in direct association with the tattooed polypectomy site, in the subserosa region (AJCC: pT3) (). Overlying the tattoo, there was a tubular adenoma (6 mm in the greatest dimension). The epithelial dysplasia resembled colonic adenoma, containing basophilic columnar cells with hyperchromatic pencillate nuclei and scattered goblet cells, reaching diagnostic criteria for adenomatous gastric epithelial dysplasia (GED) a.k.a. tubular adenoma (Figures and ) []. Multiple deeper sections were examined; there was no adenocarcinoma. In parallel to the features of the biopsy, there was no evidence of autoimmune metaplastic atrophic gastritis and the remaining gastric tissue was unremarkable.
The neuroendocrine tumor was composed of monomorphic cells with eosinophilic to amphophilic cytoplasm, round nuclei with granular “salt and pepper” chromatin, trabecular morphology, and up to 4 mitoses per 10 high power fields (Figures and ). Immunostaining for synaptophysin (SP11, Thermo Scientific) and chromogranin (LK2H10, Hybritech) was positive, and Ki-67 (K2, Leica) highlighted a proliferation index of 10–15%. Six of fifteen lymph nodes were positive for metastases.
Lymph nodes contained metastatic WD-NET as well as mucinous glands (highlighted with mucin and Alcian Blue stain) (Figures , , and ). Pancytokeratin stain (AE1-AE3, Thermo Scientific) demonstrated differential staining, with strong diffuse membranous and cytoplasmic staining of the glandular component as opposed to weaker staining of the neuroendocrine component (). CK7 (RN7, Leica) and CK20 (Ks20.8, Leica) were only positive in the glandular component and were negative in the neuroendocrine component (Figures and ). Ki-67 highlighted a higher proliferation rate in the glandular component in comparison with the neuroendocrine component (K2, Leica) (). Synaptophysin (SP11, Thermo Scientific) and chromogranin (LK2H10, Hybritech) were positive only in the neuroendocrine component (). P53 (DO-7, Leica) was predominantly negative with only rare staining, better appreciated in the glandular component. The entire tumor was negative for C-kit (CD117) (polyclonal, Dako). Immunostaining for mismatch repair proteins (MMR proteins) (Ventana: M1, EPR3947, G219-1129, and 44) highlighted retained expression throughout the tumor.
In view of mucin-containing neoplastic glands occupying 30% of the metastases and presence of a tubular adenoma in the primary gastric lesion, the tumor was classified and staged as MANEC rather than gastric WD-NET (AJCC: pT3, pN2). At the current follow-up, nearly 2 years after surgery, the patient is doing well and is without evidence of recurrence or distant metastasis on surveillance imaging.


A 62-year-old male underwent upper gastrointestinal endoscopy as a screening examination and was diagnosed with early ESCC. A 0-IIc type Lugol-voiding lesion was detected in the lower thoracic esophagus. There was no evidence of submucosal invasion by esophagography, narrow band imaging, or endoscopic ultrasonography. Pathological biopsy examination revealed well-differentiated ESCC. Computed tomography (CT) scanning detected neither lymph node nor distant organ metastases. As a result, ESD was performed as the initial therapy (Fig. ). The pathological findings demonstrated well-differentiated ESCC with invasion of the lamina propria and lymphatic permeation (Fig. ). No tumor cells were present in the proximal, distal, and radial margins. As additional therapy, subtotal esophagectomy and reconstruction were performed with a gastric tube via the posterior mediastinal route. Pathological examination of the resected specimen revealed no residual primary lesions and no metastases in any of the dissected lymph nodes. The patient had an uneventful postoperative course, with hospital discharge at 14 days after surgery.
At 3 years and 4 months after esophagectomy, enlargement of abdominal para-aortic lymph nodes was detected by follow-up CT scan and subsequently confirmed as recurrence of esophageal cancer by positron emission tomography (PET)-CT scanning (Fig. ). Two cycles of 5-fluorouracil (5-FU; 700 mg/m2 on days 1 to 4) combined with cisplatin (70 mg/m2 on day 1) and radiation (total 50.4 Gy/28 Fr) were administered, after which, the abdominal para-aortic lymph node metastases reduced markedly. At 1 year after chemoradiotherapy (4 years and 5 months after esophagectomy), left adrenal gland recurrence was found by PET-CT scan (Fig. ). The left adrenal gland tumor was resected. Pathological examination revealed that most of the normal adrenal cells had been replaced by well-differentiated squamous cell carcinoma cells with the same degree of differentiation as the primary lesion. At this time, the abdominal para-aortic lymph node metastases that had been treated with chemoradiotherapy were not detected by PET-CT scan; these nodes were therefore not resected. However, 5 months later (5 years and 1 month after esophagectomy), distant recurrence in the liver, right adrenal gland and abdominal lymph nodes, was recognized by CT scan (Fig. ). The patient died from cancer progression 3 months later (5 years and 4 months after esophagectomy).
Lymphatic permeation is rare in T1a-LPM ESCC. Kodama et al. reported that lymph node metastasis occurred in 3.3%, lymphatic permeation in 6.5%, and vascular permeation in 0.4% of T1a-LPM cases []. Yamashita et al. reported that 5-year metastasis rates for EP/LPM, MM, SM1, and SM2 ESCC were 0.4, 8.7, 7.7, and 36.2%, respectively and for mucosal cancer with and without lymphovascular permeation, 46.7 and 0.7%, respectively []. Because the present case was T1a-LPM ESCC with lymphatic permeation, the risk of lymph node or distant recurrence was considered to be low. Therefore, to eliminate the possibility of under-diagnosis, histopathological examination of the ESD specimen was repeated. Additional cutting of the specimen did not reveal any new malignancies, and the diagnosis was T1a-LPM ESCC with lymphatic permeation.
Because the para-aortic lymph node metastases were not resected and were therefore not examined pathologically, it was difficult to determine whether the adrenal gland metastasis was from the primary lesion or from para-aortic lymph node metastases. Of note, pathological examination of the metastatic adrenal tumor revealed that most normal adrenal cells had been replaced by well-differentiated squamous cell carcinoma cells with the same degree of differentiation as the primary lesion, suggesting that the metastatic adrenal tumor had originated from the primary lesion.
In cases of lymphatic permeation, the guidelines recommend that additional therapy such as surgical resection by esophagectomy or chemoradiotherapy should be considered. Because surgery enables the dissection of lymph nodes, it is expected to be a definite cure []. Motoyama et al. reported that among 17 patients with an initial clinical diagnosis of mucosal cancer without lymph node metastasis in thoracic ESCC, after ESD by additional esophagectomy with lymphadenectomy, pathological examination revealed that 5 (29%) patients had submucosal tumor invasion and the involvement of one to two lymph nodes in the lower mediastinum and abdomen. Therefore, surgical lymph node dissection is necessary and an effective treatment for this patient population []. However, surgery is invasive and is associated with serious risks such as postoperative complications and mortality. Esophagectomy may be challenging to perform in elderly patients, and those with cardiac or pulmonary complications. Saeki et al. reported that postoperative complications were observed in 10 of 34 patients who underwent additional esophagectomy after ESD. One patient died from pulmonary complications, but no postoperative recurrences were detected during the follow-up period []. Motoyama et al. reported that 4 of 17 patients (24%) who underwent esophagectomy developed an anastomotic fistula, but these were healed with conservative therapy, and surgery was not necessary. Pneumonia occurred in 3 patients (14%). Recurrent nerve palsy occurred in 4 patients (24%), but it was resolved []. These findings suggest that esophagectomy after ESD provides favorable disease control for ESCC with pT1a-MM/pSM and/or vessel permeation. Nevertheless, careful consideration should be given to the indication for an invasive surgical procedure.
Chemoradiotherapy is useful for patients with complications such as local and distant metastasis, and it plays a role in ESCC treatment by eliminating some micro-metastases. Yamamoto et al. reported that the overall survival rate of patients with clinical stage I ESCC was similar for chemoradiotherapy versus esophagectomy, despite a higher local recurrence rate after esophagectomy. Local carcinoma recurrences were treated by endoscopy in most patients, with no effect on overall survival []. Thus, chemoradiotherapy appears to be a viable alternative to esophagectomy in patients with clinical stage I ESCC. Kawaguchi et al. reported that chemoradiotherapy after ESD was an effective and safe approach for T1a-MM or T1b ESCCs. The combination of ESD and chemoradiotherapy improved the local control rate relative to chemoradiotherapy alone [].
There is accumulating evidence on the efficacy of chemoradiotherapy for early-stage ESCC. A clinical trial conducted by the Japan Clinical Oncology Group (JCOG9702) showed that the complete response rate after chemoradiotherapy with 5-FU plus cisplatin in patients with stage I ESCC was 87.5%, and the 4-year survival rate was 80.5% []. These results are similar to those reported for esophagectomy in stage I patients []. JCOG has initiated a multicenter phase III trial (JCOG0502) to evaluate the efficacy and safety of chemoradiotherapy versus esophagectomy for clinical stage I esophageal cancer. In addition, results from a phase III trial (JCOG0508) on the efficacy of ESD combined with chemoradiotherapy for clinical stage I esophageal carcinoma are anticipated.
No definitive conclusions can be drawn from the current case concerning whether esophagectomy or chemoradiotherapy constitutes optimal treatment after ESD in patients with pT1a and vessel invasion. However, because this disease is extremely rare, it would be impractical to attempt to determine the superiority of additional treatment by conducting randomized controlled trials. Further findings from multiple institutes must be reported to enable discussion of the optimal treatment strategy.


Informed patient consent was obtained for treatment. No identifying patient information is contained in this report.
The patient was a 41-year-old right-handed female who had been diagnosed with NF1 at age 6. With the exception of multiple cutaneous manifestations of NF1, she did well until 2002 when signs, symptoms, and radiographic evidence led to the diagnosis of a large tectal lesion with compression of the brainstem and obstructive hydrocephalus. This was treated with a ventriculoperitoneal (VP) shunt. She did well until 2007 when her headaches and gait imbalance recurred. Ultimately, the VP shunt was removed and an endoscopic third ventriculostomy was performed. She continued to have headaches and dizziness. The tumor had been followed with serial MRIs. The lesion was stable until May 2012, when enlargement of a cystic component with compression of the brainstem was documented on MRI (Figure ).
The patient underwent suboccipital transvermian craniotomy for subtotal resection of the tumor in October 2012. Pathology showed a low cellularity neoplasm with two major components (Figures -). These included glial fibrillary acidic protein (GFAP)-positive areas of piloid astrocytic cells resembling pilocytic astrocytoma and other areas with synaptophysin-positive neurocytic tumor cells that formed neurocytic rosettes or perivascular pseudorosettes. Dysmorphic ganglion cells were focally noted as was focal myxoid change. Rosenthal fibers and Periodic acid–Schiff–diastase (PASD)-positive eosinophilic granular bodies (EGBs) were seen. Mitotic figures were not identified. The Ki-67 nuclear labeling index was low at about 2% in the most proliferative areas.
The initial postoperative course was uneventful, and the patient was discharged for rehabilitation. However, about 2 ½ weeks postoperatively, she developed a pseudomeningocele. This was followed by pseudomonas meningitis and recurrent hydrocephalus. Over the next seven months, she had a very complicated course with multiple episodes of meningitis, urinary sepsis, and Clostridium difficile colitis. After a slow but progressive decline in functional status and multiple hospitalizations for complicated infections, her family made the decision for patient comfort care only. She expired in home hospice.


We report the case of a 75-year-old North African woman with no notable medical history, admitted for pelvic pain lasting for the last 4 months and unrelieved by analgesics; the transit was undisturbed. The symptoms were aggravated by melena and asthenia that motivated the medical consultation. A clinical examination at admission found a patient with a stable hemodynamic status, an abdominal examination revealed a palpable and mobile pelvic mass. Laboratory tests showed a hypochromic and microcytic anemia with low hemoglobin and hematocrit levels rating at 7.3 g/dL and 21%. An abdominal computed tomography (CT) scan showed a large pelvic mass measuring 11 × 9 cm involving the distal small bowel loops, the bladder dome, and the uterine body without peritoneal effusion (Fig. ). After primary care, our patient underwent an exploratory laparotomy. The intraoperative finding was a brownish pseudoaneurysmal mass of the small bowel located 80 cm from the Treitz’s angle; this mass was invading the bladder dome and the left ovary and closely adhering to the uterus (Fig. ). Limited small bowel resection with 10 cm margins on both sides of the tumor extended to the left annexes and to a portion of the bladder with end-to-end anastomosis was achieved. The postoperative management was uneventful and our patient was discharged on day 6. The surgical specimen was 18 cm in length and included a black solid tumor with exophytic growth infiltrating the small bowel wall until the mucosa (Fig. ). A histological examination revealed a malignant proliferation of large cells with prominent round nuclei and a cytoplasm with eosinophilic spots or the seat of melanin pigments. Tumor necrosis was estimated at 30%, the rest of the ileum was the seat of chronic ileitis (Fig. ). The immunohistochemical profile showed an intense and diffuse cytoplasmic positivity for HMB-45 antigens and for PS-100, suggesting a malignant melanoma (Figs. and ). An etiological investigation in search of a primary tumor of the small bowel melanoma was negative, an anoscopy, examinations of eyes and skin with multiple cutaneous biopsies were performed without finding any melanoma lesion.


A 55-year-old man with a previous history of peripheral vascular disease, CD, and hypothyroidism presented with 4 months of bilateral leg weakness and weight loss. He was a retired police officer and had been physically very strong in the past. CD was diagnosed elsewhere 5 years earlier. The details of his initial evaluation were not available. The disease was thought to be inactive and the patient was on an unrestricted diet.
The symptoms were slowly progressive. He had difficulty rising from a chair and going up stairs. He denied eyelid ptosis, diplopia, dysarthria, dysphagia, dyspnea, myalgia, fasciculations, muscle atrophy, numbness, paresthesia, and bladder or bowel problems. He had unintentional weight loss of 30 Lb. There was no loss of appetite, decreased food intake, diarrhea, or steatorrhea. Examination demonstrated 4/5 strength in the deltoids and iliopsoas bilaterally (Medical Research Council scale). There was no weakness of intermediate and distal limb muscles. Cranial nerves, reflexes, sensation, coordination, and gait were normal.
He had a 60-pack-year history of smoking and the initial investigations were focused on a possible malignancy. Laboratory workup was remarkable for macrocytic anemia and neutropenia (). Peripheral blood smear and flow cytometry showed no evidence of leukemia or lymphoma. Bone marrow biopsy demonstrated hypocellularity with no other abnormalities. Computed tomography of the chest, abdomen, and pelvis was normal. Acetylcholine receptor and voltage-gated calcium channel antibodies were negative. Serum creatine kinase and thyroid function tests were also normal. Electrodiagnostic studies (EDX) were performed per our myopathy protocol, which includes one motor and one sensory nerve conduction study (NCS) from an arm and a leg (Ulnar, tibial, and sural NCS in this case), and needle examination of multiple proximal and distal arm and leg muscles as well as a thoracic paraspinal muscle. Additionally, we performed 3 Hz repetitive nerve stimulation of the ulnar, accessory, and facial nerves. There were no abnormalities found on EDX. Further testing revealed severe copper deficiency [6 μg/dL (60–190)] and mild B12 deficiency [193 pg/mL (211–911)], as well as positive anti-gliadin and anti-transglutaminase antibodies. Zinc and vitamins D and E were normal ().
The patient underwent endoscopy and duodenal biopsy that showed moderate villous blunting, intraepithelial lymphocytosis, chronic inflammation of the lamina propria, and crypt hyperplasia. The histologic findings, in conjunction with the elevated anti-transglutaminase antibodies, confirmed the diagnosis of active gluten sensitive enteropathy or CD (). He was placed on a strict gluten-free diet and total parenteral nutrition (TPN) with micronutrient supplementation. The daily dose of copper was 2 mg. He also had weekly B12 intramuscular injections.
After 1 month of TPN, copper and other micronutrients normalized (). Anemia and neutropenia improved. Weakness resolved completely and the patient regained 10 Lb. TPN was stopped and he remained on a gluten-free diet.


A 79-year-old woman with a history of cholecystectomy and T-tube placement 36 years ago presented to our institution for evaluation of fever, abdominal pain, and elevated liver function tests. Physical examination was significant for jaundice and right upper quadrant tenderness. Laboratory investigation revealed AST 54 U/L, ALT 140 U/L, AP 221 U/L, TBil 4 mg/dL and WBC 15000/mm3. MRCP revealed severe intrahepatic and extrahepatic biliary dilatation and choledocholithiasis. ERCP showed a bulging papilla, common bile duct 1.5 cm and choledocholithiasis. A large biliary sphincterotomy and sphincteroplasty were performed. A 15 mm balloon was used for stone extraction and a significant amount of exudate was visualized. A clear plastic tubular object was visualized in the distal bile duct which upon balloon extraction proved to be a T-tube remnant ().


A 67-year-old man was admitted to the intensive care unit (ICU) due to a second exacerbation of COPD in two weeks. He came from a first aid unit, had already been through orotracheal intubation, and was receiving mechanical ventilation and antibiotics. The patient was a heavy smoker (120 pack-years of tobacco exposure) and started to claim dyspnea to great efforts over the previous few months; he had also lost 8 kg in less than a month. There was no other known comorbid condition in his clinical history. After some days of stabilization in the ICU, the patient was referred to the general internal medicine unit, where another exacerbation took place, along with fever and productive cough, likewise controlled with bronchodilators and antibiotics.
On physical examination, multiple seborrheic keratoses on the back of the hands (), elbows, and trunk were observed. They were asymptomatic and have appeared in the previous four months. These lesions alerted to the possibility of a paraneoplastic manifestation, hypothesis also considered by the dermatologists who followed the case.
The search for an occult neoplasia was then initiated. The investigation comprehended thorax CT-scan, upper gastrointestinal endoscopy, colonoscopy, and blood analysis, which pointed no malignancy. Colonoscopy showed four sessile polyps, one in the ascending colon (measuring 10 mm), histopathologically defined as a tubulovillous adenoma with high-grade dysplasia, and three in the transverse colon (the biggest measuring 9 mm), corresponding to tubular adenomas with high-grade dysplasia. Ultimately, abdomen CT-scan revealed one irregular-shaped vegetation on the bladder floor, measuring 22 × 18 × 16 mm, with no apparent adipose tissue invasion (). The patient denied previous hematuria or any other urinary symptom.
Due to an incomplete stabilization of the pulmonary condition, the patient was discharged and returned after a month for cystoscopy and transurethral resection of the bladder tumor. Histopathological examination of the removed tissue confirmed a noninvasive low grade papillary urothelial carcinoma. Control cystoscopy did not show any residual mass. Adjuvant therapy with intravesical BCG administration was then commenced.
Nine months after the start of the treatment, the patient still presented residual lesions of seborrheic keratoses, which are then pruriginous ().


A 38 year-old woman presented with progressive abdominal distension. Contrasted abdomino-pelvic CT revealed that the distended abdominal cavity of the patient was filled with low-density fluid, and showed a degree of scalloping sign on the liver surface (Fig. ). A 7-cm sized multi-locular cystic mass containing fat tissue, which was thought to be originating from the right ovary, was identified in the pelvis. However, the patient’s appendix and left ovary appeared normal. Pelvic magnetic resonance image showed cystic component with high signal intensity on T1- and T2-weighted images, and fat-saturated T1-weighted images showed a drop in the signal intensity of the right ovarian mass (Fig. ). These imaging studies suggested a teratoma of the right ovary resulting in pseudomyxoma peritonei. Colonoscopy and gastroscopy were normal. The laboratory test of tumour markers showed that CEA, CA19-9, and CA125 were elevated to 15.5 ng/ml (Upper normal limit [UNL] < 5 ng/ml), 59.8 U/ml (UNL < 37 U/ml), and 39.7 U/ml (UNL < 35 U/ml), respectively.
Importantly, the proband’s family history completely fulfilled the Amsterdam criteria (Fig. ). The mother suffered from appendiceal cancer, ascending colon cancer, and endometrial cancer, a maternal brother died of rectal cancer at the age of 51, and an older sister of the patient died of sigmoid colon cancer at the age of 31, suggesting the possible diagnosis of LS. After genetic counselling, a written informed consent was obtained from the patient, and a genetic test was performed using DNA from the patient’s peripheral blood. As a result, a germ line mutation consisting of a single nucleotide duplication of C (c.1546dupC, p.Q516PfsX3) in codon516 was identified in the MLH1 gene (Fig. ). This mutation was judged as a deleterious mutation because the duplication resulted in a frameshift mutation inducing a truncation of the MLH1 protein.
An open laparotomy was performed, where abundant mucinous ascites mixed with hair was found in the peritoneal cavity (Fig. ). In addition, surgical exploration identified a ruptured left ovarian cystic mass of 16 cm in size and a non-ruptured right ovarian cystic mass of 7.5 cm, but the appendix was normal. The patient underwent complete cytoreductive surgery (CRS) including total abdominal hysterectomy with bilateral salpingo-oophorectomy, total peritonectomy, appendicectomy, greater and lesser omentectomy, splenectomy, cholecystectomy, and resection of the liver capsule. Following the CRS, hyperthermic intraperitoneal chemotherapy (HIPEC) was added with mitomycin C at 10 mg/m2 for 1 h. The post-operative course was uneventful.
Both ovarian tumours were filled with copious gelatinous fluids containing multiple hairs and yellowish sebaceous materials (Fig. ). Histological examination revealed that the right ovarian tumour was a mature cystic teratoma accompanied by an endometriotic cyst. It was reported that 3 to 8% of primary ovarian mucinous tumours are accompanied by teratoma [–]. The teratoma-associated mucinous tumours were also described to show various histological appearances such as cystadenomatous, borderline tumour-like to adenocarcinoma, tumours with entity of goblet cell carcinoid, and low grade adenomatous mucinous tumours. Consistently, the left tumour was a mixture of mucinous cystic tumour and teratomatous lesion. Most of the tumour cells showed mild cellular atypia but complex structural changes classifying the tumour into an intermediate malignancy (Fig. ). Additionally, a part of the tumour demonstrated stromal invasion, which corresponds to moderately differentiated adenocarcinoma. The teratomatous tumours predominantly consist of ectodermal components such as skin and its adnexa, cartilage, tracheobronchial epithelium, and included mucin-producing epithelium depicting lower intestinal tract (Fig. ). Immunohistochemical study revealed that the left ovarian tumour with intermediate malignancy was negative for CK7 (Fig. ), and diffusely positive for CK20 and CDX2 suggesting that it has a lower intestinal phenotype (Fig. and ). However, the region of moderately differentiated adenocarcinoma was positive for CK7 and CDX2, and negative for CK20, indicating aberrant cytokeratin staining pattern due to malignant transformation. Histological examination of the peritoneum, omentum and implants found mucinous material and a small amount of tumour cells (pseudomyxoma). It is of note the histology of the appendix was normal. These data suggested that the pseudomyxoma peritonei may result from mucin-producing epithelial cells derived from ovarian teratoma.
To clarify the aetiology of the ovarian tumour, we carried out microsatellite instability (MSI) analysis with the Bethesda panel (D2S123, D5S346, D17S250, BAT25, and BAT26). Interestingly, the DNA from the left ovarian tumour was positive for MSI in three of the five markers (Fig. ) indicating high microsatellite instability (MSI-high). Additional immunohistochemical analysis showed positive staining for MSH2 and negative for MLH1 and PMS2 (Fig. -), which is in complete agreement with the germ line mutation in MLH1. These data suggested that the deficiency of mismatch repair system was associated with the ovarian tumour.
After the surgery for PMP, the patient was enrolled in a surveillance programme of PMP. In the 2-yearly colonoscopy, a transverse colon cancer of 2.5 cm in size was identified. The patient underwent right hemicolectomy where no recurrence of PMP was detected. Histological examination of the tumour revealed tubular adenocarcinoma of the colon with an UICC stage of pT2N0M0 (data not shown).
Since our case underwent complete CRS and HIPEC for PMP and curative operation for transverse colon cancer, a good prognosis of the patient is expected. However, if recurrent disease may appear in the patient, we may need to consider immune checkpoint inhibitors for the treatment, because mismatch repair-deficient tumours are more effective to anti-programmed death 1 (PD1) monoclonal antibodies [].


A 54-year-old woman was found to have pancreatic and hepatic tumor masses on a routine health check-up. Abdominal ultrasound showed a clearly delineated hypoechoic mass (2.4 cm × 2.0 cm) in the IVa segment of the left hepatic lobe, near the diaphragmatic dome and left hepatic vein. A pancreatic mass (4.6 × 2.2 cm) located on the dorsal aspect of pancreatic body, in front of splenic vein, was also observed (Additional file : Figure S1A-B). Hepatic contrast ultrasound revealed a significant increase in size of the mass in the left liver lobe during the arterial phase. Abdominal computed tomography (CT) revealed a heterogeneous low-density mass with an ill-defined swelling in the pancreas (Additional file : Figure S1C-F). Owing to the difficulty in performing biopsy, open operation was performed. Intraoperative macroscopic findings included a gray hard pancreatic mass in the middle segment of the pancreas and a mass in the left liver lobe. Fine needle aspiration cytology showed atypical cells. The diagnosis of pancreatic cancer could not be excluded. Radioactive 125I ion implantation for the pancreatic tumor mass, and microwave coagulation therapy for the hepatic lesions was administered. Histopathological examination of pancreatic and liver biopsy specimens demonstrated spindle cells with nuclear mitoses (1-2 per 50× high power field) (Fig. ). Immunohistochemical examination showed positive staining for Vimentin (+) (Fig. ), Discovered On Gastrointestinal tumor (DOG)-1(+) (Fig. ), Cluster of Differentiation (CD) 117 (+) (Fig. ), 60%Ki67 (+), and negative staining for S-100 (-), CD34 (-), Cytokeratin (-), Smooth Muscle Actin (SMA) (-) (Fig. ), Desmin (-), and EMA (-). A diagnosis of advanced pancreatic stromal tumor with liver metastases was made.
The patient recovered well after surgery. Oral imatinib mesylate (300 mg once a day) plus thymosin subcutaneous injection (1.6 mg twice a week for 4 weeks) were prescribed. Follow-up CT and ultrasound examinations at 6 and 10 months showed no signs of tumor growth in the pancreas and liver (Additional file : Figure S2A-D). Repeat CT at the 13-month follow-up revealed multiple hepatic nodular masses in IVa segment, V segment and the border of V and VI segments (size 0.3–0.5 cm) and right peritoneum (Additional file : Figure S2E-F).
A second surgery was performed to remove the peritoneal mass and to obtain liver biopsy. During operation, microwave coagulation therapy for liver lesions was re-administered. Immunohistochemical study of liver biopsy specimen and the resected peritoneal specimen showed positive staining for DOG-1 (weak +), Actin (+), SMA (+) (Fig. ), Caldesmon (+), Ki67 (30% +) and negative staining for CD117 (-) (Fig. ), Desmin (-), CD34 (-) and S-100 (-). Histopathological examination showed spindle cells with nuclear mitoses (14–20 per 10 high power fields) (Fig. ). Spindle shaped malignant cells with nuclear mitoses (2–5 per 10 high power fields) were also observed in the liver biopsy specimen.
The c-KIT and platelet-derived growth factor receptor α genes were sequenced. Wild-type variants were detected in exons 9, 11, 13 and 17 of the c-KIT gene and of exons 12 and 18 of the platelet-derived growth factor receptor α gene. The woman was finally diagnosed as a case of primary pancreatic leiomyosarcoma, which transdifferentiated from pancreatic stromal tumor, with liver and peritoneal metastases.
Leiomyosarcoma and its subtype, primary pancreatic leiomyosarcoma, have rarely been reported. The estimated worldwide incidence of PLMS is 1-2/100,000 population []. Baylor et al. found only five cases of primary pancreatic leiomyosarcoma in a study of 5057 patients with pancreatic cancer []. In 1951, Ross et al. reported the first case of primary pancreatic leiomyosarcoma []; since then, only 71 such cases are on record []. The gastrointestinal stromal tumor mostly arises from Cajal or its precursor cells [, ]. Histological and immunogenic properties of extra-gastrointestinal stromal tumors are similar to those of gastrointestinal stromal tumor, but the former originates from abdominal or retroperitoneal soft tissues []. To the best of our knowledge, this is the first report of a case of extra-gastrointestinal stromal tumor which progressed to primary pancreatic leiomyosarcoma.
The clinical manifestations are non-specific []. Our patient was asymptomatic prior to the diagnosis. The radiological examination for primary pancreatic leiomyosarcoma has low specificity []. Endoscopic ultrasonography-guided biopsy does facilitate a preoperative diagnosis; however, repeated sampling may be needed [, ].
Histological and immunohistochemical examination is the gold standard for diagnosis. In a study of 12 patients with primary pancreatic leiomyosarcoma, presence of more than 10/50 nuclear mitotic figures per high power field was associated with poor survival []. Xu et al. reported a median survival rate of 48 months; survival rates at 1, 3, 5 and 10 year were 66.6, 51.2, 43.9 and 29.3%, respectively []. Non-radical surgery and infiltration of surrounding organ and vessels were independently associated with poor prognosis. Another study demonstrated the presence of spindle shaped smooth muscle-like cells in primary pancreatic leiomyosarcoma, and IHC markers SMA (+), MSA (+), Desmin (+), CD117 (-), HMB45 (-), DOG-1 (-), CD34 (-) [], while gastrointestinal stromal tumors were characterized by CD117 (+), CD34 (+), DOG-1 (+), SMA (-), Desmin (-), S-100 (-) [].
Positive staining for CD117 may help differentiate between primary between extra-gastrointestinal stromal tumors and primary pancreatic leiomyosarcoma. In our study, initial immunohistochemical study of liver and pancreas specimens showed CD117 (+), while that of liver biopsy and peritoneal specimens at second- surgery detected CD117 (-) and SMA(+), which is indicative of transformation of extra-gastrointestinal stromal tumors to primary pancreatic leiomyosarcoma. Imatinib has been reported to induce differentiation of gastrointestinal stromal tumors into leimyoscarcoma [], which may have contributed to the transdifferentiation observed in our patient.


A 26-year-old male, who was a counter salesman by occupation, presented to our out-patient department with a depigmented patch over the shin of his left leg. The lesion had started five years back as a small area of hypopigmentation, which gradually increased in size over a period of three years to attain the present size. It has been stable since then with no further increase in size or no newer areas of depigmentation elsewhere in the body. He had been applying topical steroids and tacrolimus 0.1% ointment for the past three years with not much improvement. His quality of life was greatly affected by the illness as he was facing stigmatization at his workplace and among his relatives. History suggestive of keloidal tendency, bleeding diathesis, other major systemic illnesses and family history of similar illness were ruled out. On examination, there was a well- to ill-defined hypopigmented to depigmented plaque of size 15*9 cm over the middle 1/3rd of the anterior aspect of the left leg with leukotrichia at the center and few areas of repigmentation. Other parts of the skin and mucosa were normal. His baseline investigations and coagulation profile were within normal limits. Hepatitis and retroviral serology were negative. A pre-procedure photograph was taken to assess the treatment outcome (Figure ).
With written and informed consent, the patient was subjected to the ANPEH procedure. The donor site chosen was the anterolateral aspect of the right thigh for better patient convenience and color match. The area was cleaned and draped with aseptic precautions. No anesthesia was given. The harvester (Cellutome™ Harvester, Acelity, Texas, USA), (a disposable component with a cutting blade), was placed with the curved blade side upwards and secured with the Velcro strap provided. The vacuum head (a reusable component of the system that delivers negative pressure and warming from the control unit to the harvester) was then applied to the harvester ensuring a snug fit. The power of the control unit was switched on, and the skin was heated at 37°C to 41°C and a negative pressure of -400 mm Hg to -500 mm Hg was rendered and the process of formation of microdomes of epidermis began. The microdomes were visualized through the view window (Figure ). At the end of 30 minutes, round well-formed microdomes were visualized and the unit was turned off. The vacuum head was removed and a Tegaderm™ (3M, Minnesota, USA) dressing (with perforations made using an 18 G needle for exudation of serum during the postoperative days), was inserted and the blade was activated by lowering the handle. The dressing was then gently removed with the adhered microdomes (Figure ). The patient experienced a very minimal and bearable discomfort during the procedure. The donor site was dressed with sterile gauze. The recipient site was cleansed, draped and marked (Figure ). Under local anesthesia, the recipient site was dermabraded using a micromotor with diamond fraise (Figure ). The Tegaderm dressing with the grafts embedded was spread uniformly over the denuded recipient site (Figure ). The area was in turn dressed with an absorbable sterile pad which was secured in place using a dynaplast. The limb was kept immobile for 30 minutes and the patient was sent home with oral antibiotics and analgesics. He was advised to avoid strenuous activities for a week.
After a week, the dressing was removed carefully from both the donor and recipient sites. The donor site had epithelialized completely (Figure ) and the recipient site showed most of the micrografts fallen off with scab formation, leaving behind pinkish areas of the donor grafts (Figure ). The patient was followed-up every week and was assessed for the percentage of repigmentation and other complications like pain, secondary infection, cobble stoning, graft rejection, scarring, milia formation and reactivation of the disease, and the results were tabulated (Table ). Photographs were taken on each follow-up for assessment. In the subsequent weekly follow-up uniform perigraft melanin pigment islands were observed (Figure ) which gradually increased in size and coalesced to form 60-70% of repigmentation at the end of four weeks (Figure ) and a near total repigmentation (>95%) at the end of eight weeks (Figure ). At the end of 20 weeks, the pigmentation was uniform with no surface irregularities (Figure ). No other topical medications were prescribed during this period. The patient’s quality of life was assessed using Dermatology Life Quality Index (DLQI) [] once in four weeks. DLQI improved from a score of 20 to 9. The patient has been assessed for five months and will be on monthly follow-up for a period of 12 months and he is yet to receive more skin grafting for the surrounding vitiliginous patches using the negative pressure epidermal harvesting system.


A 65-year-old man with a remote history of possible PE and current tobacco use presented with swelling, erythema, and warmth of his right lower extremity for three to four weeks (). He denied cough, hemoptysis, shortness of breath, chest pain, recent travel, prolonged immobilization, or history of malignancy. Approximately ten years ago he was diagnosed with a PE at an unrecallable hospital and did not receive anticoagulation. The events surrounding this self-reported PE could not be verified.
Five weeks before presentation, the patient went to the Emergency Department with low back and right buttock pain radiating down to the mid-posterior right calf and was diagnosed with sciatica. Two weeks later, he returned with pleuritic chest pain and exertional dyspnea, thought to be secondary to costochondritis; he left against medical advice. Three weeks later, on the day of admission, he was evaluated by his primary care physician, who obtained a lower extremity venous Doppler study that showed extensive DVT in his right lower extremity ().
The patient's medications included bupropion, cholecalciferol, ibuprofen, prazosin, simvastatin, vitamin A, and over-the-counter supplements including DIM. He had used over-the-counter testosterone supplements for six months but discontinued them 13 months before hospitalization. Prior to his hospitalization, he used DIM one tablet daily for three to four months. He did not know the dose, but a common dose is 100 mg per tablet. He had a 60 pack-year smoking history, with cessation for five years prior to resumption one year ago. He had a documented weight loss of 7 kg over one month, but he endorsed a recent increase in exercise, including skiing and weight lifting. Colonoscopy four months earlier found a benign polyp. Prostate specific antigen was less than 3 ng/mL a year before and during hospitalization.
Physical examination revealed a heart rate of 104 beats per minute, blood pressure 123/81 mmHg, respiratory rate 16 breaths per minute, temperature 36.1°C, and oxygen saturation 96% on room air. The right leg was mildly swollen with erythema and warmth. The rest of the examination was unremarkable. Chemistry panel, complete blood count, hepatic function panel, and coagulation studies were normal. PE-protocol computed tomography (CT) of the chest (Figures and ) showed bilateral pulmonary artery filling defects with marked involvement of the right middle lobe branch with associated probable infarction. He was treated with anticoagulation and counseled on tobacco dependence. Five months later, a lower extremity venous Doppler study found chronic DVT in the right lower extremity ().


This is a 49-year-old female known to have cystectomy and ileal conduit in 2012. She presented to our clinic complaining of left recurrent flank pain with recurrent urinary infections. Physical examination revealed a good ileal pouch. Renal function test was within normal. Abdomen CT scan showed left lower pole renal stone with a burden of 16.4 mm (). The patient underwent left laser flexible ureterorenoscopy (L-FURS) through her ileal conduit (). Stone laser fragmentation was completely achieved, surprisingly the stone was formed over what we assume were surgical clips from the previous surgery ().


A 32-year-old woman was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. The past medical history of the patient was unremarkable. Physical examination revealed upper abdominal tenderness and mild hepatomegaly without palpable mass. The laboratory examinations showed that the routine blood test, routine stool test, and routine urine test were normal. The level of total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, carbohydrate antigen 19–9 (Ca199), carcinoembryonic antigen (CEA), and the alpha-fetoprotein (AFP) were within the normal limits. Hepatitis B and hepatitis C virus tests were negative.
The plain computed tomography (CT) scan showed a round mixed density lesion with well-demarcated margin, sized 6.5 × 6 × 6 cm, in the segment V of the right lobe of the liver (Fig. A). Contrast-enhanced CT showed it was inhomogeneous enhancement on the early arterial phase (Fig. B), and the lesion remained obvious heterogeneous enhanced in the portal phase (Fig. C). The diagnosis of the CT was hepatic hamartoma or the hepatocecullar carcinoma with hemorrhage. The patient suffered abdominal pain and the malignant tumor could not be ruled out, so the right V segmentectomy of the liver was performed in our hospital.
During the operation, we observed extensive adhesions between the tumor and the surrounding tissues, as both of them appeared hyperemia and edema. After carefully separating the adhesions, we removed the tumor step by step with Pringle maneuver. The resected specimen demonstrated a 7 × 6 × 5 cm solitary tumor with a clear margin. The external surface of the mass was white-tan to gray-red. The mass was soft, smooth, and fragile with multiple congested blood vessels. Hemorrhage was observed in part of the neoplasm, and the amount of bleeding in surgery was about 300 mL.
On microscopic examination, there was a majority of epithelioid and spindle-shaped cells with oval nuclei and clear to granular eosinophilic cytoplasm. Necrosis, cellular atypia, and nuclear atypia had not been seen (Fig. A). The tumor on immunohistochemistry showed that the lesions were positive for human melanin black-45 (HMB-45) (Fig. B), smooth muscle actin (SMA) (Fig. C), CD99, vimentin, and CD34, but the CD117, S100, CK, CK18, and Ki-67 immunohistochemistry outcomes were negative.
The correct diagnosis of hepatic PEComa was made on the basis of morphologic characteristics and immunohistochemical results. The patient recovered uneventfully and was discharged 1 week after surgery. There is no clinical or radiographic evidence of recurrence 9 months after surgery.


A 51-year-old female, who is originally from Italy, presented to the Emergency Room (ER) 24 hours after landing in the United States with increasing psychosis. Her history was only remarkable for paranoid schizophrenia, but she was highly functional at baseline. As per her family, she was hearing command hallucinations which did not improve with her usual antipsychotic medications, aripiprazole and haloperidol. Her haloperidol dosing was actually being tapered over the previous 4 months. She had no history of drug or alcohol use.
In addition to increasing psychomotor agitation, her only other complaints were profound weakness and dyspnea. Her initial vital signs revealed a systolic blood pressure of 70 mmHg, a heart rate of 118 beats per minute, and oxygen saturations via pulse oximetry of 78% on room air. The chest X-ray revealed bilateral infiltrates concerning for congestive heart failure. She ultimately progressed to requiring mechanical ventilatory support and within the first few hours in the ER was necessitating escalating doses of 3 vasopressors. Her electrocardiogram showed precordial ST segment depressions (), and the laboratory parameters were remarkable for an elevated troponin I of 14.7 ng/mL and elevated plasma brain natriuretic peptide of 1760 pg/mL. With a clinical diagnosis of worsening cardiogenic shock, she was taken urgently to the cardiac catheterization laboratory. The coronary arteries were noted to be patent, but left ventriculography revealed severe systolic dysfunction with an ejection fraction approximated at 15–20%. The ventricular wall segment analysis revealed hyperdynamic apical wall contractility and akinesis of the basal and mid ventricular walls (), a pattern consistent with an ITC. The LV end-diastolic pressure was elevated at 23 mmHg, and pulmonary artery catheter indices showed a low cardiac output of 1.7 L/min. Immediate echocardiography confirmed normal right ventricular size and systolic function, and there was no evidence of significant valvular disease or pericardial effusion.
The decision was made to proceed with left ventricular assist device (LVAD) support using an Impella 2.5 LP (Abiomed Inc., Danvers, MA) device. Over the ensuing 24 hours following Impella LVAD placement, phenylephrine, norepinephrine, and vasopressin were all tapered off. Her hemodynamic indices showed steady improvement (), and the Impella LVAD was removed 60 hours following initial placement. Her native cardiac output 24 hours following device explantation had increased to 5.4 L/min. She was weaned from mechanical ventilatory support and extubated on her fifth day of hospitalization. On the same day, a contrast echocardiography showed normalization in LV systolic function with an ejection fraction of 55–60% (). The previous akinesis involving the mid and basal ventricular wall segments was no longer present. A repeat chest X-ray showed significant clearing of the previously seen vascular congestion. She was started on a low dose of carvedilol and lisinopril and, after modification of psychotropic medications, was discharged on the seventh day of hospitalization without any evidence of psychosis and with near full baseline functionality. One year later, an email reply from the patient's primary doctor in Italy communicated that she was still doing well with a follow-up echocardiogram showing stable cardiac function.


A 35-year-old female presented with mild-moderate acne on her face. She started
treatment with isotretinoin (Roaccutane®, Roche, Basel,
Switzerland), at a dose of 30mg per day, for facial acne, which had lasted one
month. No indications of smoking or alcohol use featured in the patient's personal
history. Tests did not detect any other health problems, like hyperlipidemia,
diabetes, hypertension and congenital, or acquired heart disease. Shortly after
treatment was initiated, she complained of palpitations during exercise and rest.
Before, she had never experienced any episodes of palpitations or other symptoms
such as dizziness or chest pain. She consulted the Cardiology Department; her heart
sounds were arrhythmic upon cardiovascular examination. A 12-lead electrocardiogram
(ECG) showed premature ventricular contractions (PVCs) (). A transthoracic echocardiography revealed a normal
left and right ventricular size and function. Twenty-four-hour Holter monitoring
showed frequent single, bigeminy, trigeminy, quadrigeminy uniform PVCs.
When she was readmitted to the Cardiology Department two weeks after cessation of
isotretinoin treatment, her cardiovascular examination was normal. There were no
PVCs upon a 12-lead ECG and 24-hour Holter monitoring, or during exercise testing
(). She has remained asymptomatic
since the discontinuation of the drug.


A 66-year-old woman visited our hospital with a chief complaint of palpitations. Since electrocardiogram showed paroxysmal atrial fibrillation and echocardiography showed a thrombus in the left atrium, she was admitted to receive treatment. Echocardiography also showed pericardial effusion and circumferential thickening of the left atrial wall. The thrombus in the left atrium revealed high echoic mass, while circumferential thickening of the left atrial wall revealed low echoic lesion in echocardiography. Thus, these two parts were completely different components. To examine active inflammation or malignancy for the thickened left atrial wall, gallium-67 scintigraphy was performed. The frontal planar image showed abnormal accumulation of radioisotope (RI) in the chest (). The single photon emission computed tomography/computed tomography (SPECT/CT) fusion images showed corresponding diffuse abnormal accumulation of RI in the thickened left atrial wall (), possibly suggesting active inflammation in the left atrial wall including acute myocarditis, sarcoidosis, or amyloidosis or malignant disease such as malignant lymphoma. However, clinical symptoms and subsequent general examination showed no findings suggestive of sarcoidosis, amyloidosis, or malignant lymphoma. As the patient had no increased white blood cell count and C-reactive protein level and had no symptoms other than palpitations, she was followed up without receiving specific treatment for the atrial lesion.
Anticoagulant therapy for the thrombus in the left atrium resulted in its dissolution, and administration of a β-blocker for atrial fibrillation achieved favorable heart rate control. In the second gallium-67 scan 2 months after the first scintigraphy, the abnormal accumulation in the heart was no longer visible on the planar and SPECT/CT images (). Echocardiography showed no thickening of the left atrial wall. Regarding the cause of cardiac inflammation, acute myocarditis was considered because the serum antibody titer of cytomegalovirus was significantly elevated in a few weeks though endomyocardial biopsy was not done because the patient did not agree with it. She is now continuing follow-up check of atrial fibrillation in outpatient department.


A 24-year-old female with a history of asthma and GERD presented to the emergency room with severe chest pain, chest tightness and shortness of breath following an upper respiratory tract infection. The patient reported episodes of dry cough and runny nose one week prior to this presentation, followed by a sudden sharp pain in the center of the chest. The pain was 8/10 in intensity on the visual analog scale and pleuritic in nature, which aggravated by deep breathing and lying down flat. It was relieved by sitting up straight and did not radiate to her left arm or jaw. The patient has associated cough and high-grade fever but denied chills, wheezing, orthopnea, nausea or vomiting. She had not experienced similar complaints in the past. The patient also complained of muscle aches along the back of her neck and shoulders. She denied smoking or alcohol use.
Physical examination revealed a healthy looking African American female. Auscultation of the chest and back demonstrated slightly diminished breath sounds at the bilateral lung bases. No murmurs or friction rubs were appreciated on precordial examination. Vital signs were recorded, monitored and charted. Initially, the heart rate was 105/min but later decreased to 94/min, temperature upon arrival to the emergency department was 103.3 °F and after treatment, it improved to 98.4 °F, oxygen (O) saturation was 99% on room air and respiratory rate was 18/min.
Laboratory investigations showed low serum sodium levels suggesting hyponatremia secondary to hypovolemic state, high aspartate aminotransferase (AST) and alanine transaminase (ALT) levels, possibly due to an underlying infection (Table ). The patient was anemic but white blood cell count was elevated at 10.6 k/mm3. Acute-phase reactants such as erythrocyte sedimentation rate, C-reactive protein, and ferritin levels were high. Creatine kinase (CK) was markedly elevated with a low CK-MB relative index indicative of skeletal muscle injury. Mild increase in troponin levels was suggestive of pericardial inflammation. Positive antinuclear antibodies (ANA) and elevated levels of anti-dsDNA, anti-RNP, anti-Smith and anti-SSA/B antibodies consistent with a mixed picture of systemic lupus erythematosus (SLE), Sjögren's syndrome and polymyositis were found.
The CT scan of chest and chest X-ray are shown in Figures -. CT angiography of the chest was also performed. Axial contrast enhanced images using 100 Ml Isovue 370 intravenous contrast material with multiplanar reformations showed mild left pleural effusion as well as a small pericardial effusion with bilateral lower lobe interstitial infiltrates. There was no evidence of pulmonary embolism. Electrocardiogram (ECG) showed no apparent ST segment elevation or depression (Figure ). Echocardiogram showed small pericardial effusion, no diastolic chamber collapse, ejection fraction of 65-70%, normal left ventricular diastolic function, normal left ventricular internal dimensions and wall thickness.
In the emergency department, she was diagnosed with pericarditis based on history, but imaging of the chest showed diffuse infiltrates in the lungs indicating multifocal community acquired pneumonia for which she was treated with 250 mg Zithromax (azithromycin) PO daily, 1 g Rocephin (ceftriaxone) IV twice a day and 2 litres of intravenous (IV) fluid. The patient received Dilaudid (hydromorphone) and Toradol (non-steroidal anti-inflammatory drug) for her chest pain and possible pericarditis. She was also managed with scheduled ibuprofen 600 mg every eight hours for generalized body aches, colchicine for polyserositis, and pantoprazole sodium sesquihydrate (proton pump inhibitor) 20 mg PO daily for GERD. She responded well to the medications. The patient was prescribed prednisone on a tapering dose. On the follow-up visit, her condition significantly improved although her creatinine phosphokinase levels remained elevated suggesting rhabdomyolysis and polymyositis. Informed consent was obtained from the patient for this study.


A 36-year-old African American male diagnosed with Philadelphia chromosome positive CML two years ago presented to the emergency room for the second time with a history of a one-month progressively worsening weakness involving his left upper extremity, along with numbness and severe pain. His symptoms during the previous hospital evaluation were attributed to musculoskeletal causes after stroke was ruled out. Although he was unsure, he was reported by family members to have developed some facial asymmetry during this time. He had been noncompliant with his treatment with dasatinib, being irregular and casual in his approach to prescribed medication intake, and his primary oncologist was concerned with CML progression at an accelerated phase after having undergone a bone marrow biopsy. He was meanwhile awaiting the results of a recent cervical lymph node biopsy.
On neurological examination the patient was noticed to have left-sided ptosis, miosis, enophthalmos (), and reported facial anhidrosis on the left side, alongside ipsilateral weakness predominantly involving his intrinsic hand muscles, long finger flexors, and numbness involving the medial border of his arm, hand, and little finger (see Video 1 in Supplementary Material available online at ). The rest of his motor power was 5/5 throughout, with restriction of an accurate evaluation of his left upper extremity, due to exquisite pain-limited range-of-motion of the whole limb. Deep tendon reflexes were 2+ throughout. Plantar reflexes were down going bilaterally and no sensory level was appreciated. His findings were concerning for left Horner's syndrome and lower trunk brachial plexopathy, while the rest of his general physical examination was significant for scattered, nontender cervical lymphadenopathy.
His blood count revealed marked leukocytosis with a total leukocyte count of 102 × 109/L, predominated by myeloid precursors, 4% promyelocytes, 3% myelocytes, and 12% metamyelocytes. An electrodiagnostic study was deferred due to lack of patient cooperation from the pain. An MRI of the cervical spine and brachial plexus with and without contrast was performed. This revealed the presence of a bulky left paraspinal soft tissue mass (), extending from the C6 to T3 level, measuring 3.9 × 6.8 × 7.8 cm, anteroposterior, transverse, and cephalocaudad dimensions, respectively. This also involved the left C6 to T1 nerve roots and extended into the supraclavicular and retroclavicular segment of the left brachial plexus over approximately 6.8 cm in length, most consistent with leukemic infiltration. Extension into the spinal canal on the left was noted from C6/7 to the bottom of the T1 level without cord compression, along with abnormal bone marrow signal intensity involving the posteromedial first rib and left anterior scalene muscle, all again consistent with leukemic infiltration. Extensive lymphadenopathy was noted on imaging studies (), particularly involving the submandibular, left, and right internal jugular lymph nodes. The excisional biopsy of right cervical lymph node, meanwhile, confirmed myeloid sarcoma or chloroma with immunophenotyping revealing 32% blasts displaying myeloid-associated antigen expression and aberrant expression of CD5, CD7, and CD 117 (). In view of the collateral histological findings, his neurological presentation was attributed to a paraspinal chloroma with regional leukemic infiltration of the left lower brachial plexus, and a final diagnosis of CML with extramedullary myeloid blast crisis was made. He was started on aggressive induction chemotherapy with a 7 + 3 regimen (7 days of cytarabine at 100 mg/m2 plus 3 days of idarubicin at 12 mg/m2) in addition to resuming dasatinib. He was also initiated on radiotherapy of 10 fractionations to a total of 3000 centigray (cGy) for the paraspinal chloroma. Bone marrow biopsy on Day 14 was hypocellular with no blasts identified or evidence of residual leukemia. Repeat Computed Tomography of soft tissue neck showed interval decrease in size of his cervical lymphadenopathies and paraspinal soft tissue mass. His postchemotherapy, inhospital course was complicated with neutropenic fever, clostridium difficile diarrhea, and multifocal pneumonia with pleural effusion from which he gradually recovered. At the time of hospital discharge, his neurological deficits continued to persist. Allogeneic bone marrow transplantation and prophylactic intrathecal liposomal cytarabine (given his high risk for CNS involvement) were discussed as part of the postremission treatment plan.


A 68-year-old woman fell on her right side with her right elbow flexed while carrying her luggage. After the trauma, she found her elbow in a valgus position and repositioned the joint herself through flexed and internal rotation. She was admitted to the emergency center of our hospital because of right elbow pain and deformity. She presented with a flexed elbow and the hand placed on her abdomen. The neurologic examination revealed mild numbness in her 4-5th digits only. The radial pulse was palpable. Anteroposterior and lateral radiographs of the elbow showed lateral convergent displacement of the radius and ulna relative to the humerus without fracture signs ().
Upon diagnosis of lateral elbow dislocation, we attempted closed reduction under sedation with 15 mg pentazocine hydrochloride and 25 mg hydroxyzine hydrochloride i.m. as well as local anesthesia with 10 mg lidocaine.
The reduction maneuver was performed in the image intensifier room with the patient in the supine position. Initially, we attempted gentle longitudinal traction on the axis in the flexed position with an assistant holding the axilla as a countertraction while simultaneously checking lateral images of the elbow. After the first try was unsuccessful, we applied longitudinal traction on the axis in the stretched position while checking anteroposterior images of the elbow. The operator distracted her wrist distally and moved the dislocated proximal forearm medially. After this maneuver, we felt a click; however, the image intensifier revealed that the elbow joint was not reduced fully, and we suspected that only the ulnohumeral joint was reduced on the trochlea of the humerus (). The operator gently pushed the radial head with the elbow flexed and we heard a click to indicate full reduction. Postreduction radiographs were obtained without signs of fracture (). Though obvious varus and valgus instability of the joint was observed, redislocation was not observed in the range of motion from 30° to 90° (). Elbow arthrography revealed a completely torn medial collateral ligament (MCL) and a suspected partial tear of the lateral collateral ligament (LCL, ). CT scan and MRI revealed no sign of fracture and additional information. A motor nerve conduction velocity study of the ulnar nerve revealed decreased velocity and prolonged latency.
The elbow joint was immobilized at 90° of flexion with the forearm in supination in a posterior plaster cast for 3 weeks. Mild physiotherapy started at 2 weeks after the trauma and the elbow was examined weekly. The plaster was removed 3 weeks after the trauma. After 8 weeks, the elbow range of motion was from 0° to 125°, supination to 90°, and pronation to 90° (). Radiographs revealed mild calcification around the anterior articular capsule, MCL, and LCL; however, the patient did not complain of elbow pain (). The decreased velocity and prolonged latency of the ulnar nerve improved steadily (). Medical examination 20 weeks after trauma measured her grip strength at 17 (right)/19 (left) kg, and she had not experienced any trouble in daily living. At 6 months, she had no sensory disturbance distributed by the ulnar nerve, and her score of the DASH -JSSH: Japanese Society for Surgery of the Hand version of the Disability of Arm, Shoulder, and Hand questionnaire [] was 0.86.