Search

Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a tumor that has morphologically recognizable both adenocarcinoma and neuroendocrine carcinoma components comprising at least 30% of either components. MANEC occurring in the ampulla of Vater is extremely rare, and only 16 cases have been reported in the English language literature. In the present report, we describe the first case of MANEC of the ampulla of Vater with immunocytochemical analyses. An 82-year-old Japanese male was incidentally found to have a tumorous lesion in the ampulla of Vater. Endoscopic ultrasound-fine needle aspiration (EUS-FNA) of the tumor was performed. The Papanicolaou smear demonstrated the presence of different three components. The most dominant component was cohesive clusters of small round cells with round to oval nuclei with powdery chromatin and scant cytoplasm, which corresponded to small cell carcinoma. The second component was an adenocarcinoma, which was composed of irregularly overlapping clusters of tall columnar cells with large round to oval nuclei containing conspicuous nucleoli. The third component was an adenoma, which was comprised of flat cohesive clusters of columnar cells without atypia. Immunocytochemical analyses demonstrated that synaptophysin was expressed in the small round cells, and cdx-2 was expressed in all three components. Accordingly, a cytodiagnosis of MANEC with adenoma component was made. Preoperative diagnosis of ampullary MANEC is difficult. However, this report clearly demonstrates three different components in the EUS-FNA cytological specimen. Therefore, we suggest that cytological examination is a useful method for diagnosis of MANEC of the ampulla of Vater.

Atypical polypoid adenomyoma (APA) is a rare mixed epithelial and mesenchymal tumor characterized histopathologically by the presence of disorganized hyperplastic glands with cytological atypia embedded in intersecting fascicles of fibromuscular stromal cells. Herein, we report the first documented endometrial cytological case of APA. A 35-year-old Japanese female presented with irregular menstrual cycles and then was found to have polypoid lesions of the endometrium. Cytological examination of the endometrium and endometrial curettage were performed. The Papanicolaou smear revealed the presence of abundant clusters of crowded glandular cells in a clean background. These clusters exhibited irregular branching and dilatation, and these glandular cells had mild to moderately enlarged round to oval nuclei. Within the dilated glands, metaplastic squamous cells (squamous morules) were observed. The most striking feature was the presence of short fascicles of the spindle cells without atypia around the dilated atypical glandular cell clusters with squamous morules. Histopathological and immunohistochemical examinations revealed a diagnosis of APA. Our report demonstrates that the characteristic cytological feature suggestive of APA is the presence of short fascicles of the spindle cells without atypia surrounding dilated atypical glandular cell clusters with squamous morules in a clean background, and their appearance can allow cytologists/cytopathologists to consider APA in differential diagnosis in the endometrial cytological specimens. Diagn. Cytopathol. 2017;45:345-349. © 2016 Wiley Periodicals, Inc.

Aims Most thymic carcinomas express the lymphocyte marker CD5 aberrantly. This study was performed to examine the role of the self-reactive CD5 antigen in thymic carcinoma. Methods and results We examined CD5 expression in thymic carcinoma in relation to the lymphoid stroma. All cases of thymic carcinoma examined expressed CD5. A number of CD5+ lymphocytes were also present in the stroma of thymic carcinoma. The CD5+ tumour areas were predominantly in contact with the lymphoid stroma, and the expression level was significantly lower in tumour cells than lymphocytes. Although p53 and Bcl-2 expression levels were significantly higher in thymic carcinoma than normal thymic epithelial cells (TECs), they did not differ between CD5+ and CD5− areas. E-cadherin expression in thymic carcinoma was comparable with that of normal TECs, and it also did not differ between these areas. In contrast, both Ki-67 index and mitotic activity were significantly higher in thymic carcinoma than normal TECs, and they were significantly higher in CD5+ than CD5− areas. Conclusions CD5 may be induced by interaction with CD5+ lymphoid stroma, and may be related to tumour proliferation. CD5 induction may also be a significant and/or specific effect of the tumour microenvironment of the thymus.

A case of malignant rhabdoid tumor (MRT) occurring as a primary hepatic neoplasm in a 12-month-old Japanese female infant is presented. The patient had a slight fever for 2 weeks and presented with a palpable mass in her left hypochondrial region. After admission, the hepatic artery was embolized due to intra-abdominal hemorrhage arising from the tumor. The patient received chemotherapy with cisplatin, cyclophosphamide and adriacin. Despite treatment, the patient developed dyspnea, pancytopenia and disseminated intravascular coagulation. Rupture of the tumor resulted in death within 3 weeks. A limited abdominal autopsy revealed that the liver weighed 1240 g and was occupied by multiple hemorrhagic and/or necrotic tumor nodules. Histologically, neoplastic cells had an abundant eosinophilic cytoplasm containing paranuclear inclusions, and vesicular nuclei with a centrally located prominent nucleolus. Ultrastructurally, the cytoplasmic inclusions were composed of whorled filaments measuring 10 nm. Immunohistochemically, almost all of the neoplastic cells were positive for vimentin and cytokeratins (CK) 8 and 18, some were positive for CK 7 and 19, while none were positive for CK 1, 10, 13-17 and 20. The tumor cells did not express desmin, myoglobin, and alpha-fetoprotein. We found 18 cases of MRT of the liver published in English language literature and then, adding the present case, we summarized the 19 cases. Hepatic MRT is an uncommon neoplasm. However, it should be considered in the differential diagnosis of an aggressive liver neoplasm in childhood.

A metallothionein (BmtA) and a CPx-ATPase (Bxa1) have been identified and characterized from the cyanobacterium Oscillatoria brevis. Both bmtA and bxa1 expression can be markedly induced in vivo by Zn2+ or Cd2+. Over-expression of bmtA or bxa1 in Escherichia coli enhances Zn2+ and Cd2+ tolerance in the transformant. Dynamic studies on the expression of two genes showed that the maximum expression of bxa1 induced by Zn2+ and Cd2+ was much quicker than that of bmtA, suggesting distinct physiological roles of metallothionein and CPx-ATPase in the handling of surplus metal.

Objective We recently identified 3 fractions of human peripheral blood (PB) dendritic cells (DC), including the monocyte-associated fractions 1 and 2 (CD1a+,CD11c+ and CD1a−,CD11c+, respectively) and the lymphoid-associated fraction 3 (CD1a−,CD11c−). We attempted to determine whether these fractions were altered in Sjogren's syndrome (SS). Methods We examined 23 patients with primary SS and 22 normal control subjects. DC were purified from PB and analyzed by flow cytometry. Immunohistochemical staining of labial salivary glands of SS patients was performed with monoclonal antibodies against fascin, which is known to be specific for DC. Results The total numbers of PB DC and fraction 1 DC were decreased in SS. Immunohistochemical staining demonstrated that fascin+,CD11c+,HLA–DR+ mononuclear cells were present and scattered among numerous fascin-hyperfiltrating cells in SS patients. Interferon-γ (IFNγ)–producing Th1 cells were shown to be increased in both PB and salivary glands of patients, indicating the presence of general IFNγ-producing Th1 polarization in SS. Furthermore, numbers of Th1 cells were increased when naive T cells were cocultured with fraction 1 DC in vitro. Conclusion These findings suggest selective trafficking of fraction 1 DC into focal sites of inflammation and subsequent promotion of Th1 balance, suggesting a novel pathogenesis of SS.

A case of mucinous carcinoma of the breast with neuroendocrine differentiation in an 89-year-old woman is presented. The patient presented with a rapidly growing right breast mass, which she had had for 2-3 years. The tumor, 15 x 8 x 5 cm, was located mainly in the upper outer quadrant. Light microscopy revealed a pure mucinous carcinoma of type B. Neuroendocrine differentiation was demonstrated by Grimelius stain and chromogranin A, as well as the presence of neurosecretory granules. The breast cancer cells were of luminal origin and had dedifferentiated to attain neuroendocrine properties.

An autopsy case of squamous cell carcinoma of the uterine cervix, which developed cardiac intracavitary metastasis in a 28-year-old Filipina, is reported. At autopsy, the right ventricle contained a soft, red-purple, cauliflower-like mass. Histologically, this mass was made up of sheets of malignant squamous cells similar to the primary uterine foci. The metastases were extensive and associated with multiple organ involvement. Although this case was stage Ib at operation, vascular invasion at the primary site was characteristic, and the intracavitary tumor of the right ventricle developed without myocardial involvement. The carcinoma of the primary site extended along the inferior vena cava and settled as an intracardiac obstructive mass. A literature review (including the present case) disclosed only 14 uterine cervical carcinomas with right intracavitary metastasis. The mean age of these patients was 46 years of age (range, 28-77 years). The clinical stage was Ib in two cases, IIa in one case, IIb in six cases, and IIIb in two cases. The prognosis of these cases was poor; 13 of the patients died at an average of 19.1 months after diagnosis.

Two unrelated adult sibling cases (36- and 32-year-old females) of juvenile hyaline fibromatosis are presented. The parents of one of these patients were non-consanguineous but natives of a small island, and one elder sister among four siblings was affected with the same disease. The parents of the other patient were consanguineous, and one other sibling suffered from the identical disease. Both patients presented with multiple subcutaneous nodules, which they had had since infancy, and had undergone numerous surgical excisions. Light microscopy examination of skin lesions from both patients showed identical histology; an abundance of a homogenous, amorphous, eosinophilic extracellular matrix in which spindle-shaped cells were embedded. Electron microscopically, the spindle-shaped cells had hypertrophic Golgi apparatus and dilated, rough endoplasmic reticulum. Fine fibrillar and granular material-filled structures, the contents of which were occasionally released into the extracellular matrix, were also seen. Immunohistochemically, the spindle-shaped cells were vimentin-positive but negative for alpha-smooth muscle actin and S-100 protein, and the hyaline ground substance was positive for type I and type III collagen but negative for type II and type IV collagen and tenascin. Matrix metalloproteinase-1, -2, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2 was positive but TIMP-1 was negative. A review of 39 cases of juvenile hyaline fibromatosis in the literature is also presented. In summary, skin lesions may be the most outstanding symptoms of juvenile hyaline fibromatosis, but joint contracture and gingival hypertrophy precede the skin manifestation.

Background. Carcinoma arising in the gastric remnant many years after partial gastrectomy for benign disease, referred to as gastric remnant cancer (GRC) is well known, and many causal explanations have been proposed. Elsewhere, Epstein-Barr virus (EBV) involvement has been demonstrated in a small but significant fraction of gastric cancers, and evidence has been presented suggesting that, in positive cases, EBV may have played a causal role. The present report is concerned with EBV involvement in GRC in particular. Methods. Paraffin sections from 48 cases of GRC were studied by EBER-1 in situ hybridization. Results. Thirteen cases (27.1%) showed uniform hybridized signals restricted to the carcinoma cells in contrast to no hybridization in the normal mucosa, intestinal metaplasia, or hyperplastic epithelium. The prevalence of EBV involvement in GRC was significantly higher (P < 0.0001) than in gastric carcinomas from 1825 nonremnant cases; the difference remained highly significant even when the comparison was restricted to nonremnant cancers arising in the cardia and middle stomach, for which EBV- positive rates were highest. Conclusion. The EBV may play an important role in the carcinogenesis of GRC.

Epstein-Barr virus (EBV) involvement in gastric carcinoma has been demonstrated by the presence of EBV genomes and EBV-encoded small RNA (EBER) in the carcinoma cells, monoclonal proliferation of EBV-infected carcinoma cells and elevated antibody titers. The present study was conducted to investigate the prevalence of EBV involvement among gastric carcinomas observed in nine Japanese cities with varying gastric cancer rates. In situ hybridization of EBER-1 was applied to paraffin sections from 1848 carcinomas observed in 1795 cases and EBV involvement was detected based on uniform hybridization in carcinoma cells. Epstein-Barr virus was detected in 6.6% of lesions and 6.7% of cases. The rate of EBV involvement did not vary significantly for each city and there was no correlation with underlying gastric cancer mortality rates. Thus, geographic variation of gastric cancer rates within Japan cannot be explained in terms of EBV involvement. Epstein-Barr virus-related gastric carcinoma is one of the most common EBV-related tumors in Japan. The involvement of EBV was significantly more frequent among males than among females, mainly for cancers occurring in the upper and middle part of the stomach, and exhibited more variation by cell type among males. These observations suggest that other factors yet to be discovered may modulate the causal role of EBV in gastric carcinogenesis.