[Liver failure caused by recurrent biliary bleeding associated with Osler's disease: a case report].

A 34-year-old female patient with epigastric pain was admitted to our hospital. She reported an underlying condition of Rendu-Osler-Weber disease and a history of coil embolization for pulmonary arteriovenous fistula. A blood test revealed high hepatobiliary enzyme levels. An abdominal contrast-enhanced computed tomography revealed numerous arterioportal and arteriovenous shunts in the liver and a high-density area in the bile duct, which was diagnosed as biliary bleeding. She underwent transpapillary biliary drainage by endoscopic retrograde cholangiopancreatography, but recurrent biliary bleeding caused cholangitis, which was complicated by multiple liver abscesses. She was awaiting her turn for liver transplantation from brain-dead donors, but the liver abscesses were difficult to improve. Further, liver failure, septic pulmonary embolism, and disseminated intravascular coagulation were complicated. Thus, recurrent further biliary bleeding resulted in hemorrhagic shock, which required frequent blood transfusions. Furthermore, the continuous abscess to the intrahepatic bile duct in the anterior superior segment penetrated her diaphragm, causing hemothorax and eventually, death. Establishing progressive treatment, including liver transplantation, is considered necessary for this intractable disease.

Gastric Carcinoma With Sebaceous Differentiation and SALL4 Expression.

A sebaceous carcinoma is rarely seen in extracutaneous sites. We present a 75-year-old man who was admitted with epigastralgia and melena. Endoscopic examination revealed an ulcer on the posterior wall of the gastric antrum, and distal gastrectomy was performed. Histopathological examination revealed thin to thick trabeculae of polygonal cells with scattered foci of foamy cells, whereas Sudan 3 staining showed lipid vacuoles. Immunohistochemistry was positive for both p40 and SALL4. After considering these findings, we suggest sebaceous differentiation as the diagnosis. To the best of our knowledge, this is the first case of gastric carcinoma with sebaceous differentiation.

Extramedullary relapse of acute myeloid leukemia in brachial plexus after allogeneic stem cell transplantation: a case report.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for acute myeloid leukemia. However, extramedullary relapse of acute myeloid leukemia can occur after hematopoietic stem cell transplantation, causing treatment failure. Extramedullary relapse rarely involves the peripheral nerves, and it is not influenced by the effect of the graft on leukemia. CASE PRESENTATION: We report a case of extramedullary relapse of acute myeloid leukemia in the brachial plexus of a 41-year-old woman treated with allogeneic hematopoietic stem cell transplantation (HSCT). Complete hematological remission was confirmed by bone marrow examination 1 month after HSCT, and she developed no major complications immediately after HSCT. The immunosuppressant was discontinued 5 months later. However, 2 weeks after immunosuppressant withdrawal, the patient developed left arm pain and paresthesia, with subsequent development of a mass in the left brachial plexus. She was initially diagnosed with brachial plexus neuropathy because of concomitant graft-versus-host disease. Despite the administration of immunosuppressive agents, the mass continued to enlarge. The biopsy of the lesion revealed leukemic relapse. Thus, the patient was diagnosed with extramedullary relapse and underwent radiotherapy, resulting in tumor shrinkage. CONCLUSION: Extramedullary relapse should be considered a differential diagnosis in post-transplant patients with leukemia presenting with paresthesia.

Aggressive behavior of anaplastic undifferentiated carcinoma arising from the hilar bile duct.

BACKGROUND: Undifferentiated carcinoma of the biliary tree is extremely rare, and biliary undifferentiated carcinoma mostly originates from the gallbladder. We herein present a case of anaplastic undifferentiated carcinoma of the hilar bile duct and reviewed the literature. CASE PRESENTATION: The patient was an 81-year-old male with obstructive jaundice. Contrast-enhanced computed tomography (CT) showed a protruded tumor located at the hepatic hilum. Obstructive jaundice was relieved by endoscopic drainage. Endoscopic biopsy revealed carcinoma without glandular differentiation, and the patient was diagnosed with resectable hilar undifferentiated carcinoma. During the 5-week preoperative examination, the tumor increased in size from 23 to 45 mm. Left hemi-hepatectomy and extrahepatic bile duct resection were performed, and there were no postoperative complications. Histological findings demonstrated that the tumor was mainly composed of non-cohesive polygonal neoplasms with pleomorphic nuclei, and was diagnosed as anaplastic undifferentiated carcinoma of the common hepatic duct (T2a N0 M0 Stage II). One month after surgery, the patient was readmitted to our hospital with pyrexia due to cholangitis, and liver nodules suggestive of multiple liver metastases were detected by CT. Three months after surgery, the patient died of multiple liver metastases. CONCLUSIONS: This is the first case report of undifferentiated cholangiocarcinoma with anaplastic features. Anaplastic undifferentiated carcinoma of the hilar bile duct showed preoperative rapid growth and early relapse despite a cancer-negative surgical margin.

Clinical Diagnosis of Toxoplasmosis via Histopathological and Antibody Examination of Five Immunocompetent Patients at Kobe City Medical Center General Hospital, 2008 to 2015.

Congenital toxoplasmosis, commonly known as TORCH, is a well-known syndrome, but even experienced obstetricians rarely encounter it. In Japan, there is good overall hygiene and raw or wild game meats are not eaten; therefore, the prevalence of Toxoplasma gondii infection and the antibody positivity rates have been low. This low prevalence rate also relates to the fact that Toxoplasma gondii infections are rarely observed in immunocompetent hosts. Exploration of the cases in which pathological examinations were performed at our hospital (Kobe City Medical Center General Hospital) revealed that acquired Toxoplasma infections were apparent in five immunocompetent patients over an 8-year period. The number of infections was unexpectedly high. The number of 5 cases was the highest in literature review to the extent that we could know. To prevent congenital toxoplasmosis, which manifests as intracranial calcifications, hydrocephalus, and chorioretinitis in severe cases, pregnant women and their doctors require proper knowledge about the risk factors and danger of this infection. We believe that from the viewpoint of cost performance relationship, it is appropriate to bear the test fee of about 50 USD for Toxoplasma IgG and IgM check for the test of congenital toxoplasmosis, if patients desired.

Cytogenetic complexity and heterogeneity in intravascular lymphoma.

AIMS: To characterise the karyotypic abnormalities and heterogeneities in intravascular lymphoma (IVL). METHODS: G-banded karyotyping was performed on biopsy specimens from a single-centre IVL cohort comprising intravascular large B-cell lymphoma (IVLBCL, n=12) and NK/T-cell lymphoma (IVNKTCL, n=1). RESULTS: Five IVLBCL cases and one IVNKTCL case (total 46%) were found to have normal karyotypes, and the cytogenetic abnormalities observed in the other seven IVLBCL cases (54%) were investigated further. These seven karyotypes were uniformly complex with an average of 13 aberrations. The seven cases all had abnormalities involving chromosome 6, with 57% involving structural abnormalities at 6q13, and chromosome 8, with 43% involving abnormalities at 8p11.2. In addition, 71% had aberrations at 19q13. On average, 4.4 chromosomal gains and losses were detected per case. Cytogenetic heterogeneities were observed in six cases (86%) and tetraploidy in three cases (43%). There was no significant difference in progression-free survival (p=0.92) and overall survival (p=0.61) between the IVLBCL cases with complex and normal karyotypes. CONCLUSION: Approximately half of IVLBCL cases had a highly heterogeneous pattern of karyotypes with different clonal numerical and structural chromosome aberrations.

Real-time imaging of head and neck squamous cell carcinomas using confocal micro-endoscopy and applicable dye: A preliminary study.

OBJECTIVES: Confocal laser endomicroscopy (CLE) is a technology that enables microscopic visualization of lesions in real-time (optical biopsy) and has been successfully applied for clinical use in gastroenterology. Recently, it was also introduced for head and neck squamous cell carcinoma (HNSCC) diagnostics. We previously designed a self-made CLE, which can provide bichrome images, with topical contrast agents that are safe for use in patients. Herein, we report findings of a pilot study using our self-made CLE to image pairs of normal and cancerous tissues. This study aimed to characterize the features of HNSCC compared with normal mucosa and to establish a methodology of in vivo real-time optical biopsy of HNSCCs. METHODS: HNSCC tissues were acquired from 10 patients who underwent surgical resection. Dissected specimens were first evaluated for their auto-fluorescence spectral profiles with 473 nm laser excitation and further optical observation. While obtaining the image, auto-fluorescence spectrum and intensity of the reflectance fluorescent signals were measured in real-time by a spectrometer. Subsequently, acriflavine was applied to the specimen to fluorescently label the nuclei and observe the difference between normal and cancerous tissues with 473 nm laser excitation. Finally, double staining with acriflavine and edible Food Red No.106 was performed to observe both nuclei and the cytoplasm of normal and cancerous tissues at 473 nm and 561 nm laser excitation. RESULTS: Lower signals were detected from auto-fluorescence images of cancer tissues than normal tissues with 473 nm laser excitation. After acriflavine application, there was a clear difference between cancer and normal mucosa in the uniformity of nuclear size and shape. In normal mucosa, cells were arranged in an orderly manner, with each cell resembling a frog's egg. By contrast, in cancer tissues, the cell density was higher, and the cellular arrangement was less orderly. Using both acriflavine and Food Red No.106, images became more vivid, but more complicated because red dye staining of the cytoplasm emerged as fluorescence at different wavelengths. CONCLUSIONS: Real-time in vivo imaging using the newly developed CLE and conditions may be used to distinguish cancer tissue from normal mucosa without invasive biopsy.

Successful Treatment of a Mixed Neuroendocrine-Nonneuroendocrine Neoplasm of the Colon with Metastases to the Thyroid Gland and Liver.

Patients with mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the colon have poor prognosis. Herein, we report a patient with MiNEN of the colon with metastases to the liver and the thyroid gland, with long-term survival. A 45-year-old man presented with anterior neck swelling. Histopathological examination of the thyroid tumor revealed neuroendocrine carcinoma (NEC), suggesting that a primary NEC in another organ had metastasized to the thyroid gland. Computed tomography to identify a primary NEC revealed two tumors: one in the liver and one in the transverse colon. A biopsy revealed that the histopathology of the liver and colon tumors was NEC and adenocarcinoma, respectively. Thereafter, the patient underwent surgical resection of the colon tumor and was finally diagnosed as colon MiNEN with metastases to the thyroid and liver. The surgical resection of the metastatic liver tumor was performed after several courses of systemic chemotherapy, and the patient survives presently without any recurrence for approximately seven years after the diagnosis. Surgical resection of each metastatic lesion combined with systematic chemotherapy apparently improved the prognosis of MiNEN of the colon with distant metastases.

Tumour content ratio matters for detecting epidermal growth factor receptor mutation by cobas test in small biopsies; a retrospective study.

BACKGROUND: Recent studies indicate the benefit of treatment with osimertinib over that with conventional epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for untreated EGFR-mutated non-small cell lung cancer (NSCLC). Cobas ver2 is the only companion diagnostic method for detecting EGFR mutations with osimertinib treatment. We clinically experience false negative cases with this test, but its actual sensitivity is unknown. Moreover, no study has suggested the importance of tumour dissection, and most facilities do not routinely perform them on small biopsies. The purpose of this study was to evaluate the sensitivity of cobas in clinical practice and clarify the role of dissection as a component of the cobas testing. METHODS: We examined 132 patients with EGFR-mutated NSCLC diagnosed by bronchoscopy and confirmed with PCR clamp. Patients were tested with cobas and the EGFR-positive rate was calculated. Samples with undetected EGFR mutations were retested after tumour dissection and the rate of samples whose EGFR mutation was corrected to positive was assessed. To evaluate tumour cellularity, the tumour content ratio was assessed by calculating tumour cell count over the total cell count on the slide. RESULTS: The positive rate of EGFR mutation identification was 76% with cobas, although EGFR mutation-negative patients retained responses to TKI therapy equivalent to positive patients did; however, the tumour content ratio of negative samples was significantly lower than that of positive samples. Twenty-nine negative samples underwent dissection and 24% were corrected to positive. Moreover, 53% of the samples with a tumour content ratio below 10% was negative for cobas, but 33% of these turned positive after dissection. CONCLUSIONS: Cobas had a high false negative rate in clinical practice, and tumour content ratio might be associated with this rate. Dissection could improve the sensitivity of cobas, especially in samples with low tumour cellularity.

Clinical Value of Fused PET/MRI for Surgical Planning in Patients With Oral/Oropharyngeal Carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate the usefulness of fused positron emission tomography (PET)/magnetic resonance (MR) images for surgical planning in patients with oral/oropharyngeal cancer and suspected mandibular invasion. STUDY DESIGN: Individual cohort study. METHODS: Eleven of 17 patients with suspected mandibular invasion of squamous cell carcinoma of the lower gingiva, oropharynx, and buccal mucosa who underwent 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) and contrast-enhanced MR imaging (MRI) and had fused PET/MR images were enrolled in this study. The area for surgical resection was determined based on the fused images. The usefulness of these images was confirmed by comparing them with the histopathologic findings in the resected tumors. RESULTS: Histopathologic evaluation of the surgical specimens revealed that nine of the 11 patients had invasion into the mandible and/or medial pterygoid muscle. All patients had a negative surgical margin. The sensitivity and specificity for detection of mandibular/medial pterygoid muscle invasion was 100%/40% and 83%/100% by fused PET/MRI, respectively, and 100%/20% and 100%/60% by PET/CT, respectively. Interobserver reproducibility between two radiologists/nuclear medicine physicians and two head and neck surgeons showed that the only statistically significant κ values were for PET/MRI. CONCLUSIONS: PET/MRI can be easily understood by head and neck surgeons, who are not diagnostic imaging professionals, and can be used when planning the area to be surgically resected in patients with oral/oropharyngeal cancer and clinically suspected mandibular invasion. Considering the expense of a hybrid PET/MRI system, creation of a fused PET/MR image would provide a reasonable and reliable tool for clinical use in these patients. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:367-374, 2020.

[A Case of Renal Oncocytosis with Bilateral Multiple Renal Masses].

A 63-year-old man with microscopic hematuria underwent contrast-enhanced CT, which showed multiple bilateral renal masses. Percutaneous biopsy results indicated renal oncocytosis. The tumors remained unchanged for 3 years. Renal oncocytosis is a very rare tumor, but it is an established disease entity characterized by numerous oncocytic tumors and diffuse (sporadic) renal parenchymal epithelial oncocytic changes on an analysis histopathology. Although renal oncocytosis can be sporadic or part of Birt-Hogg-Dube syndrome (BHDS), our case did not associate with BHDS because of absence of lung cyst.

Intravascular NK/T-cell lymphoma: clinicopathological and integrated molecular analysis of two cases provides a clue to disease pathogenesis.

AIMS: To elucidate the clinicopathological and molecular features of intravascular NK/T-cell lymphoma (IVNKTCL). METHODS: Two cases of IVNKTCL were retrieved from a single-centre cohort composed of 25 intravascular lymphomas. Whole-exome and RNA sequencing and immunohistochemistry were performed. RESULTS: We identified somatic mutations in the following epigenetic regulators: four histone genes (HIST1H2AN, HIST1H2BE, HIST1H2BN and H3F3A), histone deacetylase (HDAC5), two helicases (WRN and DDX3X), two methylation-related enzymes (TET2 and DNMT1) and the SNI/SWF pathway (ARID1A). Copy number analysis identified driver gene alterations comprising the loss of ARID1B, HACE1 and SMAD4, and the gain of SOX2 and histone clusters. RNA sequencing analysis did not indicate the presence of any fusion gene. Both cases were positive for Epstein-Barr virus (EBV) and showed strong expression of programmed death-ligand 1 (PD-L1). CONCLUSIONS: This study raises the possibility that, at least for some patients, IVNKTCL may be considered an epigenetic disease with EBV infection-associated aetiopathogenesis.

Substantial improvement in immune thrombocytopenic purpura associated with T-cell/histiocyte-rich B-cell lymphoma treated with chemotherapy: A case report.

Immune thrombocytopenic purpura (ITP) is characterized by antibody and immune platelet destruction, occasionally leading to life-threatening hemorrhage. ITP is a frequent complication of chronic lymphoid leukemia, but is rarely associated with diffuse large B-cell lymphoma (DLBCL). We herein describe a case of ITP associated with T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL), which is a rare variant of DLBCL. A 54-year-old man presented with fever, multiple lymphadenopathies, petechial purpura and intraoral mucosal hemorrhage. Laboratory data revealed thrombocytopenia, normal white blood cell count, mild anemia, no active viral infections, and no autoimmune antibodies. Multiple lymphadenopathies were observed on computed tomography. A bone marrow biopsy revealed minor hypercellularity with increased number of megakaryocytes; however, there were no pathological cells or phagocytic cells. The patient was diagnosed with ITP; concurrently, he was also diagnosed with T/HRBCL via lymph node biopsy, and was treated accordingly with a chemotherapeutic regimen comprising rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone. Prompt reduction in the size of the superficial lymph nodes and an increase of the platelet count were observed simultaneously. To the best of our knowledge, this is the first report of T/HRBCL complicated by ITP. The findings strongly suggest a causative association between ITP and T/HRBCL.

The impact of early diagnosis on the prognosis of extranodal NK/T-cell lymphoma with massive lung involvement: a case report.

BACKGROUND: Pulmonary non-Hodgkin lymphoma (NHL) is rare. The most frequent subtype of pulmonary NHL is low-grade B-cell lymphoma, such as lymphoma of mucosa-associated lymphoma tissue. Extranodal natural killer cell/T-cell lymphoma, nasal type (ENKL) is characterized by predominant extranodal involvement and association with Epstein-Barr virus (EBV). ENKL with massive lung involvement has been infrequently reported, and its prognosis is extremely poor. CASE PRESENTATION: A 20-year-old Japanese man presented with intermittent fever lasting for 2 months. Radiological imaging demonstrated multiple nodules of uneven shape and size in both lungs. Video-assisted thoracic surgical lung biopsy showed abnormal lymphocyte infiltration, which was positive for CD3, CD56, and perforin. In situ hybridization for EBV-encoded RNA was positive. From these findings, he was diagnosed with ENKL with lung involvement. The patient was successfully treated with intensive combinational chemotherapy followed by allogeneic cord blood transplantation. He has been alive with continuous complete remission for 1 year after diagnosis. CONCLUSIONS: Although ENKL involving the lung has been reported to have dismal outcomes, our patient showed long-term survival after intensive chemotherapy and up-front allogeneic hematopoietic transplantation. The present case highlights the importance of early diagnosis as well as allogeneic transplantation.

Encapsulating peritoneal sclerosis in a patient after allogeneic hematopoietic stem cell transplantation: a case report.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a chronic clinical syndrome of acute or subacute gastrointestinal obstruction seen mainly in patients undergoing peritoneal dialysis. Although there are a few reports on EPS developing in non-peritoneal dialysis patients, it has not been reported in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Here, we report a case of EPS after a second HSCT. CASE PRESENTATION: A 46-year-old man with myelodysplastic syndrome showed relapse after HSCT and received a second HSCT. The patient was diagnosed with chronic graft-versus-host disease (cGVHD)-associated serositis because of persistent ascites. His ascites improved gradually and disappeared without immunosuppressive therapy. He presented with nausea, weight loss, and constipation 1 year after improvement of ascites. Computed tomography revealed no organic obstruction, but did reveal dilated, thickened, and adhered small bowel loops with a mass-like appearance. He was diagnosed with EPS on the basis of clinical symptoms and image findings. He received corticosteroid therapy (20 mg/body) without any improvement in symptoms. He developed recurrence of myelodysplastic syndrome at 1 month after initiation of corticosteroid therapy. This progressed into acute myeloid leukaemia after 3 months. He died 31 months after the second HSCT. At autopsy, the small and large intestines had formed extensive adhesions and showed signs of progressive fibrosis with peritoneal sclerosis, fibroblast swelling, fibrin deposition, and inflammatory cell infiltration, which confirmed the diagnosis of EPS. CONCLUSION: This case suggests that EPS may complicate patients with cGVHD-associated serositis. Although the mechanism of EPS development is not clear, clinicians should be aware of this eventuality.

Case Report: Acute Generalized Exanthematous Pustulosis Caused by Praziquantel.

Praziquantel is widely used for treating parasitic infections globally, especially in countries with endemic schistosomiasis. However, severe hypersensitivity to praziquantel has rarely been reported. We report the case of a 30-year-old Japanese man who developed acute generalized exanthematous pustulosis (AGEP), which is a rare and severe cutaneous reaction usually triggered by drugs, after taking praziquantel. During medical examination, eggs of Diphyllobothrium nihonkaiense were found in his stool. He took praziquantel 600 mg for 1 day and developed skin rashes and fever the next day. Pruritic generalized maculopapular erythematous eruptions were observed over the entire body. He had elevated white blood cell count, liver enzymes, and C-reactive protein level. We prescribed acetaminophen, fexofenadine hydrochloride, loxoprofen sodium, and topical ointments including difluprednate and hydrocortisone. Over the next 3 days, he developed pinhead-sized, non-follicular pustules on his diffusely erythematous skin. Histological findings of the pustular lesion showed spongiform subcorneal pustules with perivascular inflammatory cells. Approximately 8 days after taking praziquantel, the pustules resolved with desquamation. He became afebrile on day 9 and his laboratory parameters returned to normal levels on day 16. He was diagnosed with AGEP caused by praziquantel. Physicians need to be aware that praziquantel could cause AGEP, although it is generally considered a safe drug.

Clinicopathological analysis of clinically occult extrapulmonary lymphangioleiomyomatosis in intra-pelvic and para-aortic lymph nodes associated with pelvic malignant tumors: A study of nine patients.

The clinicopathological and immunohistochemical characteristics of clinically occult extrapulmonary lymphangioleiomyomatosis in lymph nodes (LN-LAM) being dissected during surgical staging of pelvic malignancy have not been well investigated. We assessed samples from nine female patients (median age, 61). None had past or familial history of tuberous sclerosis and had LAM lesions other than LN such as lung. The primary malignancies included four endometrial endometrioid carcinomas, one endometrial carcinosarcoma, three ovarian serous carcinomas and one urothelial carcinoma. Median follow-up was 43 months. The number of affected LNs ranged from 1 to 15 (median, 2) with sizes ranging from 1 to 13 mm (median, 3.0). Six cases had clinically occult LN-LAM only within the pelvic LNs, two only within para-aortic LNs, and one within both pelvic and para-aortic lymph nodes. Immunohistochemically, LAM cells exhibited a strong diffuse positivity for ß-catenin and E-cadherin in all nine cases. Clinically occult LN-LAM mainly affects peri- or post-menopausal women. On rare occasions, occult LN-LAM may manifest as systemic LAM, including in the lung. ß-catenin and E-cadherin carry potential utility as additional diagnostic markers.