Sakae Hata

Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions : a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and 'adenoma malignum'

Gastrointestinal phenotype in cervical adenocarcinomas was examined by immunohistochemistry and correlated with morphologic features. Antibody panels included anti-MUC2, MUC6, CD10, chromogranin A (CGA) and HIK1083. In addition, expression of p16INK4, a cyclin-dependent kinase inhibitor which is expressed in a variety of high-risk HPV-related conditions, was studied. A total of 94 invasive adenocarcinomas including 20 minimal deviation adenocarcinomas (MDAs) and 72 adenocarcinomas in situ (AIS) were examined. MDAs were most frequently positive for HIK1083 and/or MUC6, two representative gastric markers, with a rate of 95%, followed by intestinal-type adenocarcinomas (IAs) with a rate of 85% whereas only 27% of 56 usual endocervical-type adenocarcinomas (UEAs) were positive. MUC2, a goblet cell marker, was positive in 85% and 25% of IAs and MDAs, respectively, while in only 14% of UEAs. CD10 was positive in 15% of IAs, indicating incomplete intestinal differentiation without a brush border in most of the cases. CGA-positive cells were frequently seen in MDAs and IAs with rates of 60% and 62%, respectively. Nuclear and cytoplasmic p16INK4 positivity was identified in 93% of UEAs, whereas 30% of MDAs were positive for p16INK4. Results in AISs were comparable to their invasive counterparts, but morphologically usual-type AISs identified in eight cases of MDA were frequently positive for HIK1083 (75%) and MUC6 (63%), and p16INK4. Of note was the existence of lobular endocervical glandular hyperplasia (LEGH) with atypical features including cytologic abnormalities, and/or papillary projection, which were identified in this study in pure form (n=3) or in association with MDAs (n=6), but not in cases of other types of adenocarcinomas. These observations indicate that gastrointestinal phenotype is frequently expressed in MDAs and IAs, and there seems to be a possible link between MDA, and LEGH and morphologically usual-type AIS with gastric immunophenotype in histogenesis. Frequent absence of p16INK4 expression in MDAs suggests a possibility that high-risk HPV does not play a crucial role in development of MDAs, in contrast to the majority of endocervical adenocarcinomas. p16INK4 immunohistochemistry appears to be a promising diagnostic tool, but pathologists should be aware of frequent negative staining in MDAs, which can be a source of erroneous diagnosis.

Lobular endocervical glandular hyperplasia is a metaplastic process with a pyloric gland phenotype

Lobular endocervical glandular hyperplasia is a metaplastic process with a pyloric gland phenotype

Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: An immunohistochemical study

CD10 has been demonstrated to be positive in endometrial stromal sarcoma (ESS) and thus is useful in establishing the diagnosis, but its expression in malignant müllerian mixed tumor (MMMT) and müllerian adenosarcoma remains to be clarified. In this study, 12 cases of MMMT (9 uterine, 2 tubal, and 1 metastatic), 6 cases of müllerian adenosarcoma (three corporeal, two cervical, and one tubal), and 7 cases of primary uterine sarcomas had their tissues examined immunohistochemically for expression of CD10, desmin, myoglobin, α-smooth muscle actin (SMA), and cytokeratin. Of the primary uterine sarcomas, two were primary rhabdomyosarcomas (one cervical and one corporeal), two were ESSs, two were high-grade leiomyosarcomas, and one was a high-grade endometrial sarcoma. Sarcomatous components in all cases of MMMT and müllerian adenosarcoma, as well as all uterine sarcomas, were positive for CD10, showing moderate to marked staining intensity with varying distribution except in one MMMT, which showed weak and very focal staining. In four MMMTs, three adenosarcomas, and one rhabdomyosarcoma, myoglobin- and/or desmin-positive rhabdomyoblastic cells were positive for CD10. The immunoreactivity for CD10 showed the same distribution for α-SMA and myoglobin in three and two MMMTs, respectively. In five cases of MMMT, carcinomatous components were focally positive for CD10, and in two cases small populations of round or short spindle cells in sarcomatous components were positive for CD10, α-SMA, and cytokeratin (CAM5.2). These results indicate that CD10 expression is not restricted to ESS but can be positive in MMMT and müllerian adenosarcoma as well as in a variety of uterine tumors including high-grade leiomyosarcoma and rhabdomyosarcoma. CD10 expression might be one of the characteristics of müllerian system-derived neoplastic mesenchymal cells.

Reappraisal of synchronous and multifocal mucinous lesions of the female genital tract: a close association with gastric metaplasia

Aims:  To describe the gastric phenotype of synchronous mucinous metaplasia and neoplasms of the female genital tract (SMMN–FGT).

Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology

In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well‐established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin‐dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH).

Basement Membrane Material in Ovarian Clear Cell Carcinoma: Correlation with Growth Pattern and Nuclear Grade

Stromal hyalinization in ovarian clear cell carcinomas has been suggested to be caused by deposition of basement membrane (BM) material, but the biological and diagnostic significance of this finding remains unknown. The distribution of BM material in 17 primary ovarian clear cell carcinomas was examined semiquantitatively using hematoxylin and eosin-stained sections and immunohistochemistry with antibodies to laminin and type IV collagen. For comparison, other surface epithelial tumors, including 8 serous tumors of low malignant potential, 10 serous adenocarcinomas, 6 mucinous tumors of low malignant potential, 5 mucinous adenocarcinomas, 6 endometrioid carcinomas, 4 Brenner tumors, 1 transitional cell carcinoma, and 3 undifferentiated carcinomas, were examined. Stromal hyalinization was found in all 17 clear cell carcinomas and was immunoreactive for type IV collagen and laminin. Other types of surface epithelial tumor lacked these findings. In clear cell carcinoma, areas showing a papillary pattern tended to show abundant deposition regardless of nuclear grade, whereas in solid, tubular, or cystic areas, the deposition was more prominent in areas showing high-nuclear-grade features (grade 2 and 3) than in areas with low-nuclear-grade features (grade 1). Dense deposition of BM material recognized as stromal hyalinization on hematoxylin and eosin-stained sections in primary ovarian clear cell carcinoma is a characteristic feature that is not seen in other ovarian surface epithelial tumors. This matrix production correlates with high-nuclear-grade features and papillary growth pattern.

Usefulness of immunohistochemistry for differential diagnosis between benign and malignant breast lesions

Immunohistochemistry (IHC) is routinely performed during pathology practice for various breast lesions. Hormone receptor and HER2 analysis for primary breast carcinoma and cytokeratin staining for sentinel lymph nodes analysis are widely conducted. In addition to those markers, there are several situations in which certain IHC staining is valuable as an ancillary tool. This manuscript will present three useful examples of IHC for making differential diagnosis between benign and malignant lesions. Case 1 is an intraductal papilloma with solid epithelial proliferation, for which diagnosis was resolved by myoepithelial markers and high-molecular-weight cytokeratins (HMWCKs). Case 2 is a noninvasive ductal carcinoma with solid and papillary morphology. Many cases with such morphology mimic benign papillomas, but expression of neuroendocrine markers may lead to the correct diagnosis. Case 3 is a benign complex sclerosing lesion, with recognition of a pseudoinvasive process by myoepithelial markers. Although IHC results were excellent in these cases, they are effective only for limited situations. It is important to use IHC with caution, and re-evaluation of histological findings on hematoxylin and eosin stain and clinicopathological correlation of each case is essential.

Comparative ultrastructural study of cytotoxic granules in nasal natural killer cell lymphoma, intestinal T-cell lymphoma, and anaplastic large cell lymphoma.

Abstract. Comparative immunohistochemical and ultrastructural studies were performed on five nasal natural killer (NK) cell lymphoma cases, two intestinal T-cell lymphoma cases, and eight anaplastic large cell lymphoma (ALCL) cases to clarify morphological differences in cytotoxic granules among these cytotoxic lymphomas. Nasal NK-cell lymphomas and intestinal T-cell lymphomas had fine azurophilic granules and displayed dot-like immunostaining of granzyme B- and T-cell intracellular antigen 1 (TIA-1), predominantly in the central area of the cytoplasm. Ultrastructurally, these NK-cell lymphomas and intestinal T-cell lymphomas had two types of cytotoxic granules, type-I granules (dense core granules) and type-II granules (multivesicular bodies), which have been demonstrated in normal large granular lymphocytes in peripheral blood. However, ALCLs did not have azurophilic granules, and only type-II cytotoxic granules were found ultrastructurally, even though they showed similar dot-like immunostained patterns of granzyme B and TIA-1, as seen in NK-cell lymphomas and intestinal T-cell lymphomas. Immunoelectron microscopy revealed that TIA-1 was primarily located at the periphery of the cytoplasmic granules in the NK-cell lymphoma and ALCL cases. These findings suggest that malignant lymphomas with a cytotoxic phenotype can be divided into two types, (azurophilic granule)+, (type-I granule)+, (type-II granule)+ lymphomas and (azurophilic granule)–, (type-I granule)–, (type-II granule)+ lymphomas.

Bone marrow involvement in NPM-ALK-positive lymphoma: report of two cases.

Two cases of NPM-ALK-positive anaplastic large cell lymphoma (ALCL) with bone marrow involvement are reported. These cases were recognized within a group of NPM-ALK-positive ALCLs (n = 6) by using immunohistochemistry with the ALK1 monoclonal antibody. In case 1, the bone marrow showed diffuse infiltration of round to spindle-shaped lymphoma cells with moderate fibrosis. In case 2, lymphoma cells intermingling with hematopoietic cells could only be identified by immunohistochemical staining. In contrast to the four NPM-ALK-positive ALCL cases, which showed a cohesive growth pattern in the lymph nodes, the two cases reported here displayed lymphoma cells of smaller size, and they were classified as lymphohistiocytic variants histologically. ALK1 stained small-sized components more clearly than did CD30 (HRS-4). These results suggest that bone marrow involvement of NPM-ALK-positive ALCL may be frequently associated with a histological variant showing a small-sized cell component, and that ALK1 immunostaining is a useful tool to investigate lymphomas for bone marrow involvement.

Oligodendroglioma with signet-ring cell morphology: a case report with an immunohistochemical and ultrastructural study.

A case of oligodendroglioma with signet‐ring cell (SRC) morphology arising in the right thalamic region in a 12‐year‐old boy Is described. Histopathologlcally, the tumor was a composite neoplasm consisting of typical oligodendroglioma and anaplastlc components with aggregates of SRC. Immunohlstochemlcally the SRC were negative for glial flbrlllary acidic protein (GFAP) but surrounded by GFAP‐posltlve anaplastlc cells with high‐grade nuclear features. Typical ollgodendrogllomatous components were negative for GFAP. The Ki‐67 labeling index evaluated with MIB‐1 antibody was 1.3% in the SRC component, 9.2% in the GFAP‐posltlve anaplastlc cell component, and 0.8% in the typical ollgodendrogllomatous component. Ultrastructurally, the cytoplasm of the SRC was filled with Irregularly and widely dilated clsternae of rough endoplasmic retlculum containing granular material. Intermediate filaments and a small number of other organelles were distributed in the pertnuctear and peripheral areas. Both the SRC and anaplastlc cells had slender cytoplasmic processes, although those of the SRC were short and few in number. These findings are distinct from those of SRC hitherto described in oligodendrogliomas to date, and suggest that there is a morphological heterogeneity in SRC rarely seen in oligodendrogliomas and that some examples of SRC are related to the anaplastic cells with astrocytic features in their origin.