CD8+, CD56+ (natural killer-like) T-cell lymphoma involving the small intestine with no evidence of enteropathy: clinicopathology and molecular study of five Japanese patients.

The present study reports five CD8+, CD56+ (natural killer (NK)-like) T-cell lymphomas involving the small intestine without evidence of enteropathy, from Japan. Three were intestinal T-cell lymphoma. The site of origin of the other two was not definitive. Four of five patients underwent emergency operation because of intestinal perforation. The small intestines of these patients had multiple ulcerative lesions with or without demarcated tumors. Histologically, the lymphoma cells were monomorphic or slightly pleomorphic and displayed epitheliotropism of varying degrees. Lymphoma cells of all patients shared the common phenotype: CD3+, CD4-, CD5-, CD8+, CD56+, CD57-, T-cell intracellular antigen-1+, granzyme B+. In contrast to nasal/nasal type NK-cell lymphomas, they had clonal rearrangement of T-cell receptor(TCR) genes and were negative for EBV-encoded RNA. Immunohistochemistry and genetics suggested that three cases were of alpha beta T-cell origin and two cases were of gamma delta T-cell origin. There was no evidence of enteropathy in any patient. The cases followed a clinically aggressive course with a frequent involvement of lung. According to the classification based on the recent genetic studies of European enteropathy-type intestinal T-cell lymphoma (ETL), the present cases could be classified as type 2 ETL.

Mesonephric adenocarcinoma of the uterine corpus: a case report and review of the literature.

Mesonephric adenocarcinoma (MA) is a rare tumor of the female genital tract, mainly in the cervix and vagina, which is usually associated with mesonephric remnants or mesonephric hyperplasia. In the uterus corpus, MA is as rare as mesonephric structures, and only a few cases have been previously reported. Here, we report a rare case of MA of the uterine corpus. A 73-year-old woman presented with multiple nodules in the bilateral lung. Abdominal computed tomography scan confirmed a uterine tumor measuring 8.6 cm. All tumor markers, including CA125, were within normal limits. A total hysterectomy and bilateral salpingo-oophorectomy were performed. The tumor was confined to the myometrium and showed strong resemblance to cervical MA despite the absence of mesonephric hyperplasia or remnants. The most striking pattern consisted of large sheets of small round tubules, often with densely eosinophilic secretions in the lumen. In addition, the ductal pattern simulating endometrioid adenocarcinoma was also noted. A mixture of tubular and ductal patterns, most predominantly seen, formed more complex tubules and cribriform structures. Other elements consisted of a retiform pattern, serous adenocarcinoma-like papillary budding, and glomeruloid morphology. Immunohistochemically, the tumor cells were positive not only for cytokeratin, epithelial membrane antigen, and vimentin but also for CD10 and calretinin. No staining was identified for estrogen receptor, progesterone receptor, or androgen receptor. Adjuvant chemotherapy was begun for the patient, who is alive with disease 28 months later. We review the previously published cases of MA and discuss the principal differential diagnosis of MA in the uterine corpus.

Aberrant Cdx2 expression in endometrial lesions with squamous differentiation: important role of Cdx2 in squamous morula formation.

Only a few reports have described Cdx2 expression in endometrial lesions of the uterus. Our aim was to determine whether Cdx2 expression is related to squamous differentiation in endometrial lesions. Furthermore, we examined whether there is any correlation between Cdx2 and beta-catenin, a well-known marker of aberrant nuclear accumulation in endometrial squamous foci secondary to mutation. We performed immunohistochemical analysis of 225 cases (29 normal endometrium, 28 nonproliferative conditions, 21 polyps, 46 hyperplasias, and 101 endometrioid carcinomas) that included 72 cases (4 polyps, 16 hyperplasias, and 52 carcinomas) showing morular or keratinizing squamous differentiation (SD(+)). Normal endometrium and nonproliferative conditions showed no staining for Cdx2. Whereas there was a low rate of Cdx2 positivity in SD(-) polyps (5.9%) and hyperplasias (10%), all SD(+) lesions expressed Cdx2 (P < .001). Thirty-eight (73%) of the SD(+) carcinomas were positive for Cdx2, whereas only 6 SD(-) cases (14.0%) were positive (P < .001). Furthermore, the larger the number of squamous foci, the greater the number of Cdx2-positive cells that was found. The labeling indices of Cdx2 were significantly higher in morular components than in keratinizing or glandular ones (P < .001). There was a strong correlation of the labeling indices of Cdx2 and beta-catenin in squamous foci of hyperplasias and carcinomas. Using immunofluorescence, we confirmed the coexpression of the 2 markers. The Cdx2 protein is expressed frequently in endometrial lesions with squamous differentiation, especially morular-type differentiation, and correlates strongly with nuclear beta-catenin expression. These facts suggest that Cdx2 plays an important role in squamous morula formation.

Diagnostic utility of phosphatase and tensin homolog, beta-catenin, and p53 for endometrial carcinoma by thin-layer endometrial preparations.

BACKGROUND: For the current report, the authors examined the characteristic features of morphology and molecular biology of phosphatase and tensin homolog (PTEN), beta-catenin, and p53 immunocytochemistry in endometrial carcinoma by using thin-layer cytologic preparations. METHODS: During a 6-month period, 120 endometrial samples were collected directly by using the Uterobrush, and thin-layer specimens were prepared. Immunocytochemical expression levels of PTEN, beta-catenin, and p53 were investigated by using 40 specimens of endometrial carcinoma (EC), and 30 specimens each of proliferative endometrium, secretory endometrium, and atrophic endometrium. RESULTS: For PTEN immunoreactivity, the a cutoff value of 50% PTEN expression appeared to be useful for the correct diagnosis of EC in endometrial cytology. For beta-catenin immunoreactivity, an increase in cytoplasmic and nuclear beta-catenin expression and a loss of beta-catenin expression appeared to be useful for the correct diagnosis of EC in endometrial cytology and may aid in the stratification of EC into low grade and high grade EC. For p53 immunoreactivity, the application of a cutoff score >or=4 for nuclear p53 expression appeared to be useful for the diagnosis of high-grade EC in endometrial cytology. CONCLUSIONS: Immunocytochemical findings from a combination of PTEN, beta-catenin, and p53, in addition to cytomorphologic features, appeared to be useful for the more accurate diagnosis of EC in endometrial cytology.

Utility of thin-layer preparations in the endometrial cytology: evaluation of benign endometrial lesions.

The purpose of the current study was to examine the use of thin-layer cytologic (TLC) preparation compared to conventional cytologic preparation (CCP) in the normal endometrium (proliferative, secretory, atrophic) and endometrial glandular and stromal breakdown (EGBD). During a 6-month period, we compiled 158 cases by collecting a direct endometrial sample using the Uterobrush. The material comprised 40 cases of proliferative endometrium, 42 cases of secretory endometrium, 46 cases of atrophic endometrium, and 30 cases of EGBD. The following points were investigated: (1) number of endometrial epithelial cell clumps; (2) presence of TLC > CCP cases on number of epithelial cell clumps; (3) number of condensed cluster of stromal cells; (4) presence of TLC > CCP cases on number of condensed cluster of stromal cells; (5) presence of metaplastic clumps with irregular protrusion-containing condensed stromal cluster; (6) presence of a clear background; (7) presence of blood vessel in TLC; (8) presence of blood vessel of length more than diameter of a field in object x20 glasses in TLC. (1) In all phases, the number of epithelial cell clumps per a unit area of a preparation of TLC is greater than in CCP. (2) Cells (condensed cluster of stromal cells and metaplastic clumps with irregular protrusion-containing condensed stromal cluster) of useful and adequate numbers for a diagnosis of EGBD were observed in TLC. (3) In all phases, TLC was significantly higher than CCP on the appearance of a clear background. (4) The proliferative endometrium and secretory endometrium were highly significant in comparison with atrophic endometrium and EGBD, respectively, in terms of the occurrence of a blood vessel of length more than diameter of a field in object x20 glasses. Although the preparation area of TLC is smaller than that of CCP, the preparation has a clean background so that an accurate report on the patient's condition is possible. Therefore, TLC preparation is a useful tool for the accurate and reliable diagnosis of normal endometrial phase and EGBD, because the preparation area is confined and identification of the target cell clumps is easy.

Immunohistochemical expression of PTEN and beta-catenin for endometrial intraepithelial neoplasia in Japanese women.

PTEN and beta-catenin are the most common genes for which genetic abnormalities are found in endometrioid adenocarcinoma (type I) and even in their precursors. Currently, the World Health Organization (WHO) classifies endometrial hyperplasia as a premalignant disease. However, one of the problems in the current WHO endometrial hyperplasia schema is that it is not always a reproducible classification system. Subsequently, the alternative molecular genetics and morphometric-based classification, referred to as the endometrial intraepithelial neoplasia (EIN) classification system, has been proposed. We reclassified endometrial lesions in Japanese women using the EIN category and compared them with the results of PTEN as well as beta-catenin immunohistochemistry. A total of 117 cases that were initially diagnosed as endometrial hyperplasia according to WHO classification were reevaluated histopathologically by the EIN diagnosis category. They were classified into 38 EIN and 32 benign architectural changes of unopposed estrogen (BAC), and 47 cases were excluded. In addition, for comparison, we examined 20 cases of normal proliferative endometrium (NPE). Subsequently, the expressions of PTEN and beta-catenin were analyzed immunohistochemically. Glandular epithelium was positive for PTEN in all the cases of NPE (20/20), whereas 12.5% (4/32) of BAC and 34.2% (13/38) of EIN were PTEN-null (negative). Endometrial intraepithelial neoplasia was significantly less frequently positive for PTEN than NPE (P < .025). The nuclear staining for beta-catenin was seen in 26.3% (10/38) of EIN cases, and the intensity was generally strong. Instead, none of the BAC or NPE showed positive nuclear staining. Thus, the nuclear staining was statistically more frequently seen in EIN than in the other 2 categories (P < .025 for each). In addition, 22 of 38 EIN cases (57.9%) were either PTEN-negative or nuclear beta-catenin-positive. This combination was statistically significantly more frequently seen than BAC (4/32, 12.5%) (P < .001) and NPE (0/20, 0%) (P < .0001). Immunohistochemical loss of PTEN and positive nuclear staining of beta-catenin were frequently seen in EIN but were not seen in NPE cases in Japanese women. The combination of PTEN-negative/beta-catenin-positive results may become the reliable marker for detecting EIN.

Sclerosing hemangioma with florid endobronchial and endobronchiolar growth.

Sclerosing hemangioma (SH) with endobronchial growth (SH-EG) is an extremely unusual form of SH. A case of SH-EG in a 47-year-old female is described. She suffered from a productive cough for 4 months. A chest CT scan revealed a well-circumscribed, parenchymal mass with endobronchial lesions continuously extending to the right main bronchus. Right upper sleeve lobectomy was carried out. The tumor was 4.8 x 3.5 cm in size, tan-brown, and elastically soft. It was located in the pulmonary parenchyma of the right upper lobe and continuously extended to the right upper bronchus. Furthermore, the main tumor also spread into segmental bronchi and peripheral bronchioles. Microscopically, the tumor consisted of round to cuboidal cells with papillary and solid patterns, partly showing sclerosis and hemorrhage. For 2.5 years after surgery, the patient has been well without recurrence or metastasis. Florid intrabronchial extension as seen in this case has never been documented in SH. To form an endobronchial component, it seems to be crucial that the parenchymal SH is located adjacent to the bronchus and involves it, followed by the destruction of the bronchial cartilage.

Endometrial glandular and stromal breakdown, part 2: cytomorphology of papillary metaplastic changes.

Careful cytomorphologic evaluation of abnormal endometrial lesions has made accurate and reproducible microscopic assessment possible. Histopathology of patients with dysfunctional uterine bleeding due to an anovulatory cycle usually contain endometrial glandular and stromal breakdown (EGBD) and papillary metaplasia on the endometrial surface epithelium, if an appropriate sample has been collected. We often recognized abnormal cell clumps in the cytological smears with EGBD cases. They were composed of metaplastic cells, and some irregular small projection figures were observed from the margins of the cell clumps. We describe the quantitation of metaplastic clumps with irregular protrusions (MCIP) in endometrial endocyte samples. The current study presents the cytomorphological characteristics of the metaplastic changes recognized in EGBD cases. During a 7-yr period, 144 cases for which histopathological diagnoses were obtained following endometrial curettage, after collecting a direct endometrial sample using the endocyte. The material comprised 49 cases of normal proliferative endometrium (NPE) (patients aged 28-51, average 39.9), 32 cases of EGBD (patients aged 30-67, average 49.6), and 63 cases of endometrial hyperplasia without atypia (EH) (patients aged 35-65, average 47.7). The following points were investigated: (1) the occurrence of metaplastic cells; (2) the occurrence and the frequency of MCIP; and (3) the occurrence of MCIP that contains condensed stromal clusters. Metaplastic cells were seen in 93.8% of the EGBD cases. Cytomorphologic pattern identified with MCIP was 90.6%, and its frequency showed 16.1%. The occurrence of MCIP that contain condensed stromal clusters (93.1%) showed a strong association in comparison with other lesions, such as NPE and EH. Our data appear to indicate that the appearance of MCIP with condensed stromal clusters originated from the papillary metaplasia, which occurred on the endometrial surface epithelium. The cytologic observation of those cells may be a useful indicator for providing the nature of EGBD endometrium.

Cellular features of endometrial hyperplasia and well differentiated adenocarcinoma using the Endocyte sampler: Diagnostic criteria based on the cytoarchitecture of tissue fragments.

BACKGROUND: Because cellular atypia is often limited in endometrial hyperplasia and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma), diagnostic criteria for endometrial cytology have not been fully established. New diagnostic criteria based on the composition and architecture of tissue fragments (cytoarchitecture) in the smears were used in the present study. Cytologic features are of less importance because the distinction between endometrial hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than cellular changes. Cell clumps of various size are usually collected abundantly with cytologic material using a disposable scraping device and it was noticed that those cell clumps reflected the histologic architecture. The purpose of the current study was to determine the form of the cytoarchitecture that reflects the histologic structure and to examine the cellular features in endometrial hyperplasia and Grade 1 adenocarcinoma. METHODS: The frequency of each type of cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular protrusion, and papillotubular pattern) were obtained from 49 cases of normal proliferative endometrium (NPE) (patient age range, 28-51 yrs; average age, 39.9 yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range, 35-65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with atypia (AEH) (patient age range 47-65 yrs; average age, 53.8 yrs), and 49 cases of Grade 1 adenocarcinoma (patient age range, 42-73 yrs; average age, 58.9 yrs). RESULTS: Certain characteristics of the cytoarchitecture were observed. In the NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of cases. In the EH, cell clumps with a dilated or branched pattern were found in 34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular protrusions were found in 61.8% cases, whereas a papillotubular pattern was present in 29.7% of cases. CONCLUSIONS: The results of the current study revealed that cytoarchitectural criteria appear to be more useful for the cytologic assessment of endometrial lesions, especially for the diagnosis of endometrial hyperplasia and Grade 1 adenocarcinoma.

A distinct pattern of Olig2-positive cellular distribution in papillary glioneuronal tumors: a manifestation of the oligodendroglial phenotype?

Mixed neuronal-glial tumors of the central nervous system display a wide spectrum of differentiation. Among them, the papillary glioneuronal tumor (PGNT) is characterized by pseudopapillary structures composed of astroglial cells covering hyalinized vessels, and by neurocytic, ganglioid and ganglion cells. In addition, a "nonspecific" cell type, not similar to either astrocytes or neurocytes, has been recognized since the initial reports. Recently, minigemistocytic cells and a population immunostained by anti-Olig2 antibody have also been recognized in PGNT. Olig2 is a transcription factor that is specific for the cellular phenotype of oligodendrocytes. The aim of this study was to further investigate the histological diversity of PGNT. We examined six cases of PGNT, each of which showed Olig2 immunopositivity. Minigemistocytes were encountered in three cases at close proximity to the Olig2-positive area. Olig2-positive cells were negative for glial fibrillary acidic protein (GFAP) and neuronal nuclear antigen by double immunostaining, and mainly occupied the interpapillary area laterally adjacent to the GFAP-positive cells. They had relatively small, round and vesicular nuclei, and were formerly regarded as neurocytic cells or nonspecific cellular elements. Fluorescence in situ hybridization targeting chromosome 1p failed to demonstrate any deletion. This study disclosed an additional cellular component of PGNT that is characterized by Olig2 positivity, suggestive of oligodendroglial phenotype, and the results also encourage us to investigate oligodendroglial participation in various glioneuronal tumors.

Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma.

This study concerns the significance of aberrant (nuclear/cytoplasmic) expression of beta-catenin in pancreatoblastoma (PBL). On immunohistochemistry, all seven PBLs examined showed nuclear/cytoplasmic expression of beta-catenin, predominantly in the squamoid corpuscles (SCs). In areas with acinar/ductular differentiation, few tumour cells displayed nuclear/cytoplasmic expression of beta-catenin and more than half of the tumour cells showed membranous expression. Two out of five (40%) tumours examined showed missense mutations in codons 33 and 37 of exon 3 of the beta-catenin gene. No mutation of the adenomatous polyposis coli (APC) gene was detected in two of the remaining three tumours. Amplifiable DNA for APC analysis was not obtained from the one other tumour. Immunoreactivity for cyclin D1, one of the nuclear targets of beta-catenin, was found predominantly in the SCs of the seven tumours. In contrast, the Ki-67 labelling index was 2-4% (median 3%) in the SCs and 8-18% (median 12%) in the other areas, indicating a negative correlation with nuclear cyclin D1 reactivity. These results imply that in PBLs, nuclear/cytoplasmic accumulation of beta-catenin and overexpression of its target gene cyclin D1 are not associated with the induction of tumour cell proliferation. Nuclear/cytoplasmic accumulation of beta-catenin may be related to the morphogenesis of the SCs that are considered most characteristic for PBL.

CD56-positive cells with or without synaptophysin expression are recognized in the pancreatic duct epithelium: a study with adult and fetal tissues and specimens from chronic pancreatitis.

We observed the distribution of CD56+ epithelial cells in the pancreatic duct system using 25 fetal, one infantile, 3 normal adult, 4 diabetic, and 8 chronically inflamed pancreatic tissue samples. In the early stage of gestation (12 to 17 weeks), CD56+ cells were commonly seen in the immature tubular structures. They were often continuous to pancreatic islets, and their distribution was similar to that of synaptophysin (Syn)+ cells, suggesting that they are precursors of islet neogenesis. Their number decreased in proportion to gestational age. Instead, from 24 weeks of gestation, luminal cell clusters that were common in interlobular ducts revealed CD56+. These cell clusters were unrelated to islet neogenesis and Syn expression. Similar CD56+ luminal cell clusters were also observed in cases of chronic pancreatitis, whereas they were scarce in normal adult and diabetic tissues. CD56+ cells were also occasionally seen in intralobular ducts, intercalated ducts, and centroacinar cells in cases of chronic pancreatitis. We conclude that there are two types of CD56+ epithelial cells in the pancreatic duct system: CD56+ endocrine cells are numerous during the early stage of gestation, when islet neogenesis appears, while CD56+ luminal cells may represent developmental and regenerative changes of pancreatic ducts.

A papillary glioneuronal tumor arising in an elderly woman: a case report.

The papillary glioneuronal tumor (PGNT) was first reported by Komori et al. as a type of mixed neuronal-glial tumor. It is characterized by pseudopapillary structures, composed of hyaline vessels and outsheathing glial cells, and by the proliferation of neurocytic cells admixed with ganglioid and ganglion cells. Although it is most common in young adults, it can occur in the elderly. We report a case in a 75-year-old woman, the oldest reported person with PGNT described.

Expression of thyroid transcription factor-1 in strumal carcinoid and struma ovarii: an immunohistochemical study.

Strumal carcinoid is an ovarian teratoma composed of thyroid tissue and carcinoid, intimately admixed in variable proportions. To further elucidate the histogenesis of strumal carcinoid, the expression pattern of thyroid transcription factor-1 (TTF-1) was evaluated in two cases of strumal carcinoid using immunohistochemical techniques. TTF-1 is a nuclear transcription protein that is selectively expressed in the thyroid and respiratory epithelium, and is thought to be expressed specifically in pulmonary and thyroid neoplasms. While the follicular lining cells of the strumal carcinoid showed positive staining for TTF-1, the carcinoid element was, for the most part, negative. These results confirm that TTF-1 is expressed in the thyroidal element of ovarian teratomas and also provide further evidence that the carcinoid component of the strumal carcinoid bears no relation to thyroidal differentiation.