Invasive form of ciliated muconodular papillary tumor of the lung: A case report and review of the literature.

We report a case of a 67-year-old woman with an invasive ciliated muconodular papillary tumor (CMPT) that developed in her right middle lobe. The current tumor was incidentally detected during a follow-up imaging examination for a large cell carcinoma that was resected 10 years previously. Partial removal of the middle lobe showed a 2 cm-sized, solid and myxoid tumor located in the peripheral region. Histologically, this tumor primarily consisted of ciliated columnar cells, mucous cells, and basal cells, all of which had relatively swollen nuclei and were proliferating in a lepidic or papillary/micropapillary manner. These features were consistent with those of previously reported CMPT. In addition, atypical spindle tumor cells with more swollen nuclei, which were partly continuous to less atypical basal tumor cells, were focally found and invaded fibrous stroma in a reticular fashion. Immunohistochemically, both basal cells and atypical spindle tumor cells were positive for pancytokeratin, cytokeratin 5/6, and p40. Increased p53 positivity was found in these invading spindle cells compared with basal tumor cells. Neither BRAF V600E nor V600K mutation was detected. We concluded that this tumor was an extremely rare invasive case of CMPT, possibly representing malignant transformation of basal tumor cell components of CMPT.

Non-exophytic Lambl excrescences of aortic valves: a morphological study.

AIMS: To elucidate the histopathological findings of classical Lambl excrescences (LEs) and non-exophytic LEs (non-ex LEs) without excrescent papillary features. METHODS AND RESULTS: We examined 126 aortic valves (AVs) and revealed LEs (non-ex and/or classical), non-ex LEs and classical LEs in 106, 78 and 88 AVs, respectively. The detection of non-ex LEs was challenging, but elastica van Gieson stain highlighted their presence. Non-ex and classical LEs chiefly involved the ventricular regions, favoured posterior cusps and coexisted in the same areas of 31 AVs. A possible transformation of classical LEs into non-ex LEs was suggested histologically in 39 AVs. Non-ex LEs were associated with age of >70 years (P < 0.001) and marked deformity (P = 0.007). Classical LEs were associated inversely with marked deformity (P < 0.001), but not with age of >70 years. Compared with age- and sex-matched control AVs, non-ex LEs and marked deformity in dysfunctional AVs were more common (P = 0.037 and P < 0.001, respectively), but classical LEs were less common (P = 0.021). CONCLUSIONS: Non-ex LEs have subtle features but are a common form of LEs, and seem to develop from classical LEs. AV dysfunction-related marked deformity can promote non-ex LEs.

Contrast-Enhanced Ultrasonography in Diagnosing Intravascular Large B-Cell Lymphoma Infiltrating Liver Sinusoids.

BACKGROUND Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within vasculature. This presents a diagnostic challenge due to non-specific symptoms and lack of tumor formation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) provides useful information in diagnosing FDG-avid lymphoma, but is not specific to  IVLBCL. Contrast-enhanced ultrasonography (CEUS) is useful in evaluating focal liver lesions; however, its efficacy in diagnosing IVLBCL involving the liver remains unknown. CASE REPORT We report the case of an 83-year-old woman presenting with fever, pancytopenia, liver dysfunction, and elevated LD and soluble interleukin-2 receptor levels. PET-CT showed multiple uptake lesions in the liver. We performed CEUS with Sonazoid® to evaluate the mass-like lesions; however, no nodular lesions were observed in B mode images. Systemic enhancement was seen in the early phase but no defect was observed in the post-vascular phase. The latter finding suggested preserved Kupffer cells function, excluding tumor-forming lymphoma and liver metastases. Suspecting IVLBCL, we performed a bone marrow examination, which showed sinusoidal infiltration of large neoplastic cells positive for CD20. The patient's condition deteriorated rapidly and she died 2 days after the examination. Autopsy revealed diffuse infiltration of lymphoma cells into liver sinusoids with preserved Kupffer cells, leading to the diagnosis of IVLBCL. CONCLUSIONS Our case shows that CEUS can distinguish IVLBCL from mass-forming lymphoma based on the absence of a defect in the post-vascular phase in a patient with clinically and radiographically suspected lymphoma involving the liver. This can assist clinicians to select appropriate lesions for biopsy.

Intra-adrenal bile ductules associated with adreno-hepatic fusion: a possible origin for adrenal epithelial cysts.

AIMS: To elucidate the relationship between the rare phenomenon of adrenal cysts and adreno-hepatic fusion (AHF)-related intra-adrenal bile ductules. METHODS AND RESULTS: We examined 673 right and 662 left postmortem adrenal glands. AHF was defined as an adhesion between the liver and an adrenal with closely intermingled parenchymal cells or partial absence of the capsule dividing the two organs. AHF was found in seven (1.0%) right adrenals. AHF-related intra-adrenal bile ductules were observed in four (0.6%) adrenals, and were accompanied by aberrant hepatocytes (two adrenals), microcystic changes (two adrenals) and, in one case, a 15-mm-sized cyst. The cyst-lining cells, which focally resembled the cells of the neighbouring intra-adrenal bile ductules, were positive for cytokeratin 7 (CK7), CK19 and epithelial membrane antigen, and negative for CK20, vimentin, CD34 and calretinin. Identical findings were made in bile ductules located within fused adrenals and livers. CD10 staining was weaker or absent in the microcystic or cystic bile ductules found within adrenals. CONCLUSIONS: The 15-mm cyst we describe may have been an adrenal epithelial cyst derived from AHF-related intra-adrenal bile ductules, a possible pathogenesis for the rare phenomenon of right adrenal epithelial cysts.

Fat cells and membranous fat necrosis of aortic valves: a clinicopathological study.

We examined 152 aortic valves (AVs), which included 82 postmortem non-dysfunctional AVs (nd-AVs) and 70 surgically removed dysfunctional AVs showing aortic stenosis (AS), aortic regurgitation (AR), or combined AS and AR (AS-R). Fat cells, membranous fat necrosis (MFN), and fat-MFN-related lesions composed of fat cells and/or MFN were found in 127 (83.6%), 110 (72.4%), and 140 (92.1%) of 152 AVs, respectively, and all were associated with older age (P = 0.010, P = 0.022, and P = 0.003, respectively). MFN was associated with fibrous thickening and calcification (both, P = 0.001). Nd-AV fat cells and fat-MFN-related lesions were not correlated with body mass index. Compared with age- and sex-matched control cases, MFN in AS and AS-R cases was more frequent (P = 0.030 and P = 0.045, respectively), but MFN in AR cases showed no significant differences. Fat-MFN-related lesions, possibly representing true preceding fat cells, showed no differences in AVs with and without dysfunction or in dysfunctional types. These data suggest that AV fat cells are age-related, obesity-independent, and AV dysfunction-unrelated common phenomenon. MFN is also age-dependent and could be caused by AS and AS-R, which is probably concerned with AV thickening and calcification.

Polypoid-Type Adenomyomatous Lesion of the Cystic Duct: Report of a Case and Review of Literature.

Adenomyomatous hyperplasia, a common non-neoplastic lesion in the gallbladder, is rarely identified in the extrahepatic bile duct. Typically, these lesions appear as a nodule or mural thickening/elevation. However, in exceptional circumstances, pedunculated/polypoid adenomyomatous lesion occurs in the biliary tract; two cases in the gallbladder and only one case in the common bile duct have been reported. Despite their benign nature, adenomyomatous lesions, especially those with a polypoid appearance, are clinically difficult to exclude a possibility of malignant neoplasms. We describe a case of polypoid-type adenomyomatous lesion of the cystic duct in a 72-year-old man, which was considered as a cystic duct neoplasm preoperatively. Gross examination of the resected specimen revealed that the 9 mm-sized cystic duct polyp. Histologically, the polypoid lesion consisted of glands without atypia, fibrous stroma, smooth muscle bundles, and accompanying stromal inflammation, leading to the diagnosis of benign adenomyomatous lesion. The lesion might be considered as adenomyomatous hyperplasia arising in the valve of Heister, while true nature of the lesion is uncertain. Recognition and accumulating for this rare disease will contribute to better clinical management in the future.

Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study.

AIMS: This study has attempted to elucidate the clinicopathological features of aberrant cytokeratin 7 (CK7) expression by centrilobular hepatocytes. METHODS AND RESULTS: A total of 113 liver biopsy specimens from patients with common non-neoplastic liver diseases, including hepatitis B or C, non-alcoholic steatohepatitis, alcoholic liver disease and other diseases were examined. In 56 specimens (49.6%), CK7-positive centrilobular hepatocytes (CK7 + CHs) were identified and sometimes showed binuclear features. CK7 + CHs were associated with patients' older age (P = 0.004), higher serum levels of aspartate aminotransferase (P = 0.016) and γ-glutamyltransferase (P = 0.006), centrilobular fibrosis (P < 0.001), prominent thickening of hepatocytic plates (P < 0.001) and higher scores of total and periportal CK7-positive hepatocytes (both P < 0.001), but were not correlated with gender, steatosis, serum levels of total bilirubin or alanine aminotransferase. In 55 cases of hepatitis B and hepatitis C only, CK7 + CHs were related to a higher stage of fibrosis (P = 0.006). CONCLUSION: CK7 + CHs occur relatively frequently in non-neoplastic liver disease, associated with centrilobular scarring and the presence of CK7-positive periportal hepatocytes, and appear to be a non-specific phenomenon with respect aetiology of underlying disease. CK7 + CHs may represent age-dependent activation of hepatic progenitor cells or a regenerative phenomenon of hepatocytes themselves, both of which might contribute to liver regeneration.

Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: Case report with a review of Literature.

Reported herein is an extremely rare case of primary pulmonary myxoid sarcoma (PPMS). A 31-year-old man presented with a 2.7 cm-sized pulmonary tumor surrounded by capsule-like fibrosis. The patient has been free of disease for 5.8 years after surgery. This tumor focally showed endobronchial features, and consisted of reticular cords of oval, short spindle, or polygonal cells with swollen vesicular nuclei accompanied by an abundant myxoid stroma, closely resembling extraskeletal myxoid chondrosarcoma. Tumor cells were diffusely positive for vimentin and focally positive for epithelial membrane antigen, but were negative for cytokeratin, TTF-1, Napsin A, S-100 protein, CD34, desmin, smooth-muscle actin, CD10, p63, calponin, h-caldesmon, c-kit, HMB-45, synaptophysin, or glial fibrillary acid protein. Our reverse transcription-polymerase chain reaction using the formalin-fixed, paraffin-embedded tumor tissues detected EWSR1-CREB1 fusion transcript, but could not demonstrate EWSR1-ATF1 fusion or EWSR1/TAF15/TFG-NR4A3 fusion. These findings indicate that the current tumor is an additional case of PPMS with EESR1-CREB1 fusion, recently reported by Thway et al. Some cases of PPMS can behave in an indolent manner.

Small bowel obstruction caused by appendiceal and ileal endometriosis: a case report.

Endometriosis is characterized by the presence of an ectopic endometrial gland. Intestinal endometriosis with small bowel obstruction is uncommon. In this case, a 37-year-old woman with no history of endometriosis presented with a chief complaint of abdominal pain. Computed tomography revealed a distal small bowel obstruction. Surgical intervention was performed because of the emergent abdominal condition and the potential resistance to conservative management. Histopathological examination revealed appendiceal and ileal endometriotic lesions. Preoperative diagnosis was difficult because there were no specific clinical features. Intraoperatively, it is difficult to distinguish intestinal endometriosis and bowel malignancy; thus, oncological resection should be performed.

A rare case of atypical bone marrow sarcoidosis without pulmonary involvement in a Japanese woman.

Sarcoidosis is a systemic granulomatous disease of unknown origin characterised by the presence of non-caseating granulomatous lesions. Extrapulmonary sarcoidosis with bone marrow involvement is rare and even more so without pulmonary involvement. Here, we describe a case of 69-year-old woman diagnosed as having bone marrow and hepatic sarcoidosis without pulmonary involvement based on 18F-fluorodeoxyglucose positron emission tomography findings. She was successfully treated with systemic glucocorticoid therapy.

Duodenal stenosis associated with an ectopic opening of the common bile duct into the duodenal bulb: a case report.

BACKGROUND: Ectopic opening of the common bile duct is a rare congenital biliary anomaly. Herein, we present a case of duodenal stenosis with ectopic opening of the common bile duct into the duodenal bulb. CASE PRESENTATION: A 54-year-old man was referred with fever, nausea, and vomiting. He had experienced epigastric pain several times over the past 30 years. Endoscopy showed a post-bulbar ulcer, a submucosal tumor of the duodenum, and a small opening with bile secretion. Contrast duodenography revealed duodenal stenosis and bile reflux with a common bile duct deformity. Pancreatoduodenectomy was performed because of the clinical suspicion of a biliary neoplasm or groove pancreatitis. The resected specimen showed an ectopic opening of the common bile duct into the duodenal bulb and no tumor. CONCLUSIONS: Ectopic opening of the common bile duct into the duodenal bulb is complicated by a duodenal ulcer, deformity, and stenosis mimicking groove pancreatitis or pancreatic tumors. Although rare, we should be aware of this anomaly for an accurate diagnosis.

Neuro-Sweet disease in a Japanese woman with Sjögren's syndrome.

Sweet disease (SD) is a multisystem inflammatory disorder characterised by fever, cutaneous erythematous plaques and aseptic neutrophilic infiltration of various organs. Neuro-Sweet disease (NSD) is a known rare central nervous system complication of SD. We describe a case of a 39-year-old Japanese woman who was diagnosed as NSD associated with Sjögren's syndrome. She was successfully treated with systemic corticosteroid therapy.

Pleural dedifferentiated liposarcoma: A case report.

The present case report describes a rare case of pleural liposarcoma. A 45-year-old Japanese man was hospitalized for increasing left chest pain. Imaging revealed a 10-cm pleural tumor and a 1.7-cm contralateral right pulmonary nodule. Biopsy specimens of the pleural tumor showed undifferentiated spindle-shaped and/or rounded sarcomatous features with myxoid stroma. The patient underwent embolization of the arteries feeding the left pleural tumor and palliative partial resection of the pleural tumor. The surgically removed specimens exhibited similar undifferentiated sarcomatous features. The left pleural tumor regrew aggressively, and the patient succumbed to mortality ~4.2 months following hospitalization. Autopsy demonstrated a 35-cm left pleural tumor, metastasizing to both adrenal glands and lumbar vertebral bones, and a 2.2-cm primary adenocarcinoma of the right lung. The majority of the left pleural tumor and its metastases consisted of undifferentiated sarcomatous elements, however, scattered or aggregated lipoblasts were identified in localized areas adjacent to the diaphragm. Immunohistochemically, these lipoblasts were diffusely positive for MDM2 and focally positive for S-100 protein. Undifferentiated sarcomatous tumor cells were focally positive for MDM2 but negative for S-100 protein. This case was diagnosed as pleural dedifferentiated liposarcoma. The local aggressiveness of the pleural liposarcoma directly contributed to the patient's mortality. A review of the literature indicated that the dedifferentiated subtype may serve as a factor that is indicative of a poor prognosis for pleural liposarcoma.

Idiopathic Multicentric Castleman Disease with Autoimmune Hemolytic Anemia and Production of Anti-drug Antibody against Tocilizumab.

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder, and only a few cases have been reported to be complicated with autoimmune hemolytic anemia (AIHA). A 43-year-old man who presented with multiple swollen lymph nodes was diagnosed with iMCD. He was also diagnosed with AIHA based on laboratory findings, including the results of a bone marrow aspiration study. The patient was treated with tocilizumab; however, the effect was limited, probably due to anti-drug antibodies. Tocilizumab was therefore switched to rituximab, and his anemia was improved. Complication with AIHA should be carefully considered when iMCD patients present with severe anemia.

Laterally spreading features of gastrointestinal stromal tumors: A clinicopathological study.

To elucidate the histopathological features of laterally spreading gastrointestinal stromal tumors (GISTs), we retrospectively examined 52 GISTs grossly completely resected from 50 patients. Laterally spreading features were identified in 7 GISTs (13%), and were localized within non­thickened regions of the muscularis propria adjacent to the main GISTs, ranging in length from 0.12 to 0.7 cm (mean, 0.3 cm). The laterally spreading features involved the muscular surgical margins in 2 cases. The morphologies of the laterally spreading cells resembled those of tumor cells in 4 cases, but were comprised of more slender spindle cells with smaller nuclei compared with those in the respective main GISTs. Compared with the main GISTs, KIT+ and discovered on GIST 1+ immunostaining features of the spreading lesions were similar in 4 cases, and were weaker or diminished in the other 3 cases. There were no differences in CD34+ staining features between the main GISTs and the laterally spreading lesions. One patient with laterally spreading GIST succumbed to the disease 2.5 years after the surgery, while the other 6 patients were alive without the recurrence of disease 0.4­19.2 years after the surgery. The laterally spreading features were associated with a pedunculated GIST (P=0.006), but not older age (P=0.312), sex (P=0.969), tumor size (P=0.430), mucosal invasion (P=0.666) or higher risk category (P=0.872). Results of the present study indicate that resection of a ≥1­cm muscular safety margin, and not mucosa or submucosa, is required for microscopically negative surgical margins, particularly for pedunculated GISTs.

Focal positivity of immunohistochemical markers for pulmonary squamous cell carcinoma in primary pulmonary choriocarcinoma: A histopathological study.

Cytokeratin 5/6 (CK5/6), p63, and p40 are commonly used as immunohistochemical markers for squamous cell carcinoma (SqCC) of the lung. To elucidate their positivity in primary pulmonary choriocarcinoma (PPC), the present study examined 4 PPCs, including 1 surgically removed PPC and 3 postmortem PPCs. All PPCs consisted of nested cytotrophoblastic tumor cells and occasional syncytiotrophoblastic tumor cells although 1 surgically removed PPC was markedly affected by pre-operative therapy-associated necrosis and 3 postmortem PPCs coexisted with adenocarcinoma. In 1 surgical case, a pre-operative biopsy specimen of PPC contained a few polygonal tumor cells, which mimicked SqCC and exhibited focal p40+ features. Nuclear p63+ and p40+ features of cytotrophoblast-like polygonal tumor cells were focally observed in 3 PPCs (75%) and 2 PPCs (50%), respectively. CK5/6+ trophoblastic tumor cells were focally identified in 1 PPC. Additionally, in 2 other PPCs, CK5/6+ tumor cells were scattered in choriocarcinomatous areas, but possible intermingling of CK5/6+ adenocarcinoma cells could not be ruled out. The results emphasized that PPCs could mimic SqCC morphologically and immunohistochemically, although PPC was an extremely rare neoplasm. Surgical pathologists should be aware of this diagnostic pitfall when encountering a few squamous marker-positive polygonal tumor cells within hemorrhagic necrotic biopsy specimens from lung tumors.

Intimal sarcoma of the pulmonary trunk showing broad intimal extension and focal chondrosarcomatous differentiation: an autopsy case.

We report an autopsy case of intimal sarcoma arising in the pulmonary artery with focal chondrosarcomatous differentiation. A 77-year-old woman presented with a thrombosis-like mass in the pulmonary trunk and underwent endarterectomy. Macroscopically, solid and myxomatous tumor expanded to the pulmonary valve and bilateral main pulmonary arteries. Microscopically, the tumor comprised atypical spindle cells proliferating in a fascicular fashion, as well as occasional bizarre multinucleated cells, within a myxomatous stroma. Less than 5% of the tumor cells showed chondrosarcomatous features. Immunohistochemically, tumor cells were diffusely positive for vimentin and partially positive for cytokeratin AE1/AE3, α-smooth muscle actin, and desmin. Electron microscopic analysis failed to reveal specific somatic differentiation of tumor cells. The patient died 2 days after the surgery because of uncontrollable heart failure. Upon autopsy, residual tumor cells were observed only in the left upper intrapulmonary portion of the pulmonary artery. Although the diagnosis of intimal sarcoma can be challenging, earlier histological confirmation of the tumor would lead to appropriate surgical treatment and improved outcomes.

In hepatic venous outflow obstruction, alcoholic liver disease, and nonalcoholic fatty liver disease, centrilobular scars, CD34+ vessels, and keratin 7+ hepatocytes are in close proximity.

For hepatic venous outflow obstruction, alcoholic liver injury, and nonalcoholic fatty liver disease, the term "centrizonal injury disease" (CID) is used, because injury patterns in all three entities are similar. To elucidate CID-related CD34+ vessels (sinusoids and/or microvessels) and keratin 7+ hepatocytes (K7+ Hs), we examined a series of 41 liver tissue specimens obtained at autopsy and surgery, consisting of 32 CID cases and 9 controls. Centrizonal scars were found in 21 CID cases, and these were associated with centrizonal CD34+ vessels (P = 0.009) and centrizonal K7+ Hs (P < 0.001). Centrizonal coexistence of CD34+ vessels and K7+ Hs was observed in 22 CID cases (P = 0.057). These findings suggest close centrizonal proximity of scar, CD34+ vessels, and K7+ Hs in CID. However, centrizonal K7+ Hs without CD34+ vessels were observed in 21 CID cases. CD34+ vessels were detectable in all control samples and may represent the normal vascular bed. In 29 CID cases, centrizonal CD34+ vessel density was higher than that in controls. However, most appeared to be continuous with periportal and/or interlobular CD34+ vessels, and those CD34+ vessels restricted to centrizonal regions were focal and limited in seven CID cases. Centrizonal CD34+ vessels were associated with venoportal adhesions (P = 0.027). Our findings suggest that CID induces both venoportal adhesion-related structural distortion and expansion of normally present CD34+ vessels, which may result in increased centrizonal CD34+ vessel density.

Lipomatous angiomyofibroblastoma of the vulva: A case report and review of the literature.

Lipomatous angiomyofibroblastoma is extremely rare, with only 16 cases reported to date. We herein describe an additional case arising in the left vulvar region of a 49-year-old woman. The resected 5.3-cm yellowish tumor predominantly consisted of fat cells (85% of the tumor), together with medium- and small-sized vessels, multifocal fibrotic areas and pseudoangiomatous spaces. Spindle, rounded, and/or epithelioid tumor cells proliferated in a nest and/or cord-like pattern, or singly within perivascular fibrous tissues and between fat cells. The tumor cells were positive for vimentin, estrogen receptor, progesterone receptor, B-cell lymphoma 2, and CD10, but were negative for desmin, cytokeratin, epithelial membrane antigen, S-100 protein, human melanoma black 45, C-kit and p40. Ultrastructural examination revealed that these tumor cells exhibited fibroblastic characteristics. Lipomatous angiomyofibroblastoma should be discriminated from other lipomatous tumors, including spindle cell lipoma, angiomyolipoma and cellular angiofibroma containing numerous fat cells.