Extranodal NK/T-cell lymphoma, nasal type of the uterine cervix: A case report.

We report a rare case of extranodal NK/T-cell lymphoma, nasal type of the uterine cervix that showed cytologic features mimicking cervical cancer. A 65-year-old woman presented with vaginal bleeding. Gynecological examination revealed a bulky tumor of the cervix. A conventional Papanicolaou-stained cervical smear showed hypercellularity consisting of numerous variably sized cohesive clusters that mimicked epithelial tumors, with a necrotic and inflammatory background. A small number of individually scattered cells were also identified. These scattered cells showed pleomorphic, often cleaved, or horseshoe-shaped nuclei and pale cytoplasm. Biopsy specimens revealed a diffuse growth of atypical cells with an angiocentric pattern. Extensive necrosis and infiltration of inflammatory cells were present. There were numerous mitotic figures. The tumor cells were positive for CD45RO, CD3ε, CD56, granzyme B, TIA-1, CD7, and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization, and negative for cytokeratin, chromogranin A, synaptophysin, CD4, CD5, CD8, CD20, and CD30. Based on these findings, this tumor was diagnosed as extranodal NK/T-cell lymphoma, nasal type of the uterine cervix.

Cytologic features of ovarian granulosa cell tumors in pleural and ascitic fluids.

Adult granulosa cell tumor (AGCT) is an uncommon neoplasm of the ovary with potential for aggressive behavior and late recurrence. The most important prognostic factor for AGCT is tumor stage. Thus, cytological assessment of pleural or ascitic fluids is crucial for initial staging and subsequent patient management. We report herein two cases of ovarian AGCT presenting with exfoliated tumor cells in pleural and ascitic fluid. The first case involved a 61-year-old woman who presented with stage Ic (a) AGCT. Seven years after initial diagnosis, pleural effusion and pleural dissemination were identified. The second case involved a 50-year-old woman who presented with stage IV AGCT with massive ascites and right pleural effusion. Fluid cytology from both cases showed cohesive or loose clusters of small uniform neoplastic cells with round-to-oval nuclei, coffee-bean-shaped nuclear grooves, small nucleoli, and scant cytoplasm. Call-Exner bodies were also observed in these cytologic specimens. In the differential diagnosis of small monomorphic tumor cells in pleural effusion or ascites, coffee-bean-shaped nuclear grooves and cell clusters forming Call-Exner bodies are diagnostic clues of AGCT.

Endometrial glandular and stromal breakdown, Part 4: Cytomorphology of "condensed cluster of stromal cells including a light green body".

This study was undertaken to clarify the origin of the chromophilic substance that stained in light green [light green body (LGB)] was observed in the condensed cluster of stromal cells and in the background of endometrial glandular and stromal breakdown cases. The material consists of cytologic smears of endometrial glandular and stromal breakdown (EGBD) from 58 samples in which a histopathological diagnosis was subsequently obtained by endometrial curettage. The following parameters were examined. (1) The occurrence and number of a LGB. As for the "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LBG in background," it was observed with all fields on one slide per case. When it was observed more than one in a preparation, the occurrence was determined and the number was also calculated. (2) Immunostaining of paraffin-embedded tissue sections and cytologic preparations. 1 The occurrence of "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LGB in background" was 100%, 44.8% and 91.4%, respectively. The number of "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LGB in background" was 21.2, 2.0 and 4.0, respectively. 2 When histological sections from paraffin-embedded tissue were tested by immunocytochemistry, "LGB" stained weakly or negative for fibrinogen, whereas it stained positively for CD31 and factor VIII. In addition, it stained positively for CD42b. 3 When cytologic preparation was tested by immunocytochemistry, "LGB" stained positively for CD31, factor VIII and CD42b. However, as for the fibrinogen, quantitative and qualitative evaluation of the immunocytochemical stain was not feasible due to extensive nonspecific reaction in the whole preparation. The "LGB" in EGBD cases proved to be a thrombus mostly made up by platelets, and it seemed that the recognition of the LGB showed to be a useful cytomorphological criterion for an always more accurate diagnosis of EGBD cases.

Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation.

Fetus-derived cells are present in the blood and tissues of the maternal body over a long period of time, even after delivery, resulting in fetal cell microchimerism. The exact process by which fetal cells cross the placental barrier to enter the maternal circulation is unclear. The objective of this paper was to determine the time during pregnancy that fetal cells with multilineage potential migrate to the maternal organs. Wild type female mice were crossbred with male transgenic mice, expressing enhanced green fluorescent protein (EGFP). Total hysterectomies were performed at different time points of pregnancy. On day 60 after surgery, mice were injected with either streptozotocin (STZ) to induce insulin-dependent diabetes mellitus, or vehicle. Detection and quantification of fetal cells were then undertaken in a variety of maternal organs via fluorescent microscopy and quantitative PCR amplification of the gfp transgene. In vehicle control mice, fetal cells were detected only in the maternal bone marrow. However on day 30 after STZ injection, fetal cells were detected not only in bone marrow but also in the maternal pancreas, liver and kidney. Histological analysis showed differentiated fetal cells within the pancreatic acinar cells, hepatocytes and tubular epithelial cells. Their morphological appearance was indistinguishable from their maternal counterparts, and their frequency in these organs was constant, regardless of the timing of hysterectomy. These results indicate that most fetal cells with multilineage potential in maternal tissues migrate to the maternal body early after implantation, and thereafter sustain their population over the long term after delivery.

p16(INK4a) expression analysis as an ancillary tool for cytologic diagnosis of urothelial carcinoma.

We immunochemically studied p16(INK4a) expression in 116 urine cytologic samples and compared results with 190 histologic samples. The cytologic samples were classified into 4 groups: 1, mild cellular atypia; 2, moderate cellular atypia; 3, severe cellular atypia; and 4, malignancy. Overexpression of p16(INK4a) was detected in none of 32 cases in group 1, 8 (16%) of 50 cases in group 2, 5 (42%) of 12 cases in group 3, and 11 (50%) of 22 cases in group 4. In addition, by histologic analysis, p16(INK4a) overexpression was not detected in nonneoplastic urothelium, except for a few cases of reactive atypia, but it was detected in about 50% of urothelial carcinomas. In particular, a high incidence (16/20 [80%]) of p16(INK4a) overexpression in high-grade carcinomas was noted in cytologic samples. Immunocytologic analysis of p16(INK4a) expression in cytologic samples is a useful ancillary tool for detection of urothelial carcinoma with infiltrating potential.

Endometrial glandular and stromal breakdown, part 3: cytomorphology of "condensed cluster of stromal cells".

The aim of this study was undertaken to clarify the cytological characteristic of the "condensed clusters of stromal cells," which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases. The material consists of 60 cases of cytologic smears for which histopathological diagnosis was obtained by endometrial curettage; they comprised 30 cases of EGBD and 30 cases of endometrioid adenocarcinoma grade 1 (G1). The following parameters were examined for "condensed clusters of stromal cells" in EGBD and for "clumps of cancer cells" in G1, respectively: (1) the occurrence of "condensed clusters of stromal cells"; (2) the nuclear shape; (3) a longer/shorter axis ratio in cell nuclei; (4) the area of cell nuclei; (5) the presence of overlapping nuclei; (6) nuclear crowding; (7) immunostaining. (1)"Condensed clusters of stromal cells" were only observed in EGBD. (2) A reniform nuclear shape was observed in 100% EGBD (P < 0.0001) in comparison to G1 (3%). (3) The longer/shorter axis ratio in cell nuclei, G1 (1.37 +/- 0.2) was significantly lower in comparison to EGBD (1.53 +/- 0.12, P = 0.0005). (4) Nuclear area in G1 (51.6 +/- 11.9, P < 0.0001) was significantly higher in comparison to EGBD (24.3 +/- 3.9 microm(2)). (5) The score of overlapping nuclei in EGBD (2.5 +/- 0.49) was significantly higher in comparison to G1 (1.8 +/- 0.44, P < 0.0001). (6) The nuclear crowding score was the same both in EGBD (2) and G1 (2) and these findings were not statistically significant. (7) Both CD10 and Wilms' tumor protein 1 were positive in the "condensed clusters of stromal cells" in the EGBD. The anti-cytokeratin staining was positive in "clumps of cancer cells" in the G1. The evaluation of the immunocytochemical findings by combining the Wilms' tumor 1 protein, CD10, and the anti-cytokeratin with the considered cytomorphologic features (reniform nucleus) may be useful for a correct diagnosis of EGBD in endometrial cytology.

Clinical impact of preoperative screening for gastric mucin secretion in cervical discharge by HIK1083-labeled latex agglutination test.

The present study evaluated the clinical impact of preoperative screening for gastric mucin in cervical discharge, using a latex agglutination test with HIK1083, a monoclonal antibody against gastric mucin. HIK1083-labeled latex agglutination tests were performed preoperatively using cervical secretions from 44 patients (group 1) with profuse watery vaginal discharge, multiple cervical cysts on vaginal ultrasonography, or yellowish mucin on a Papanicolaou smear and from 31 patients (group 2) with none of these clinical signs. The results were positive in 26 patients in group 1 and in no patients in group 2. Glandular lesions with a gastric phenotype were identified histologically in all 26 cases positive for the HIK1083 latex test, such as minimal deviation adenocarcinoma, lobular endocervical glandular hyperplasia (LEGH), and pyloric gland metaplasia, but not in negative cases. In 2 cases of LEGH, adenocarcinoma in situ was identified. Screening of gastric mucin in cervical discharge may facilitate preoperative detection of some early cervical adenocarcinoma.

Intranuclear cytoplasmic inclusion is a significant diagnostic feature for the differentiation of lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma of the cervix.

Lobular endocervical glandular hyperplasia (LEGH) is a cervical lesion with pyloric gland metaplasia. Minimal deviation adenocarcinoma (MDA) is an extremely well differentiated form of endocervical adenocarcinoma (AC). To date, it is difficult to differentiate LEGH from MDA because they share similar clinical, radiological, and immunohistochemical features. Furthermore, the cytological features of LEGH and MDA have not been well defined. In the present study, we describe the cytological features of LEGH and MDA. We reviewed 24 cases of LEGH (18 pure and six mixed forms) and four MDA cases of the cervix. A total of 40 cytologic smears from 28 patients were reviewed. Abundant yellow mucin was frequently present in both LEGH and MDA; however, an INCI was found in 22 of the 24 LEGH cases and it was not found in either MDA or adenocarcinoma cells associated with LEGH. Neither cell atypia nor architectural distortion was observed in LEGH. In MDA, slight cellular atypia, three dimensional, irregular cell clustering, and prominent nucleoli were observed. The presence of an INCI is a good parameter for the diagnosis of LEGH. Cytology is an effective aid in the differentiation of LEGH from MDA.

Estimation of prognoses for cervical intraepithelial neoplasia 2 by p16INK4a immunoexpression and high-risk HPV in situ hybridization signal types.

The present study used immunohistochemical staining and in situ hybridization (ISH) to examine whether progression of cervical intraepithelial neoplasia, grade 2 (CIN 2) can be predicted by p16INK4a immunoexpression and high-risk human papilloma virus (HPV) ISH signal types. We studied 52 cases histologically diagnosed with CIN 2: dysplasia regressed in 28 cases; 13 cases progressed to CIN 3; and CIN 2 persisted in 11 cases. Expression of p16INK4a and high-risk HPV signal both related to grade of CIN. Stronger p16INK4a immunoexpression and a higher frequency of expression of a punctate nuclear signal were observed in CIN 2 lesions before progression compared with those before regression. CIN 2 cases in which moderate to strong immunoexpression of p16INK4a and a punctate signal were observed simultaneously progressed to CIN 3 in 10 (91%) of 11 cases. CIN 2 cases with moderate to strong immunoexpression of p16INK4a and a high-risk HPV punctate signal should be treated because of the great risk of progression.

Lobular endocervical glandular hyperplasia as a presumed precursor of cervical adenocarcinoma independent of human papillomavirus infection.

OBJECTIVES: The aim of this study was to investigate differences in the process of carcinogenesis between adenocarcinoma coexistent with LEGH and conventional adenocarcinoma. And we intend to describe appropriate treatment plans for LEGH in this study. METHODS: Using the surgical pathology files of patients who visited the University of Yamanashi Hospital, Yamanashi Central Hospital and Kofu Municipal Hospital between 1996 and 2005, pathological diagnoses were reevaluated based on criteria for the diagnosis of LEGH by Nucci et al. As for the cases including adenocarcinoma with LEGH: (a) we created a map showing position of the LEGH component and adenocarcinoma component and squamo-columnar junction (SCJ) in HE-stained specimens, (b) immunohistochemical staining was performed using antibodies to CEA, HIK1083 and p53, and (c) detection of HPV DNA was performed using PCR and in situ hybridization (ISH). RESULTS: Endocervical adenocarcinoma was observed coexistent with LEGH in 5 cases (19.2%). (a) LEGH was located in a remote place from the SCJ. Sizes of lesions in the 5 cases ranged from 18 to 35 mm in width and 7 to 16 mm in depth. (b) HIK1083 was diffusely immunopositive in the cytoplasm of LEGH component and focal immunopositive in 4 cases with adenocarcinoma component. Immunopositivity for CEA was seen in the cytoplasm of adenocarcinoma component in 4 cases. Immunopositivity for p53 was seen in adenocarcinoma component nuclei in 2 cases. (c) HPV DNA was not detected using PCR and ISH in either LEGH or adenocarcinoma components. CONCLUSIONS: The present study suggests that clear differences exist in the process of carcinogenesis between adenocarcinoma associated with LEGH and conventional adenocarcinoma. LEGH may represent a precursor of cervical adenocarcinoma independent of HPV infection. As LEGH displays characteristics of precancerous mucinous adenocarcinoma, surgical treatment should be considered for LEGH growing beyond a certain size.

p16INK4a overexpression independent of human papillomavirus infection in lobular endocervical glandular hyperplasia.

A high rate of human papillomavirus (HPV) infection has been reported in cervical cancer and precancerous lesions. Many studies also have shown that p16INK4a overexpression is of diagnostic value for high-risk HPV-related cervical cancer and precursors. Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. There is one report about HPV infection and few studies on p16INK4a expression in LEGH. Therefore, we 1) detected HPV infection and examined p16INK4a expression and 2) observed the relationship between HPV and p16INK4a overexpression in LEGH. The immunohistochemical expression of p16INK4a was studied in 24 cases of LEGH. HPV DNA was also evaluated in these cases using a polymerase chain reaction technique. Strong (++) p16INK4a immunoreactivity was observed in 10 (41.7%) of the 24 LEGH cases; a moderate (+) pattern was observed in 9 (37.5%) cases; a weak (+) pattern was observed in 2 (8.3%) cases; and the remaining 3 (12.5%) cases showed negative expression. Overall, p16INK4a overexpression was seen in 87.5% of the cases (21/24). HPV DNA was not detected in any of the 24 LEGH cases. These results suggest that p16INK4a overexpression is independent of HPV infection in LEGH.

Absence of human papillomavirus infection in minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia.

The human papillomavirus (HPV) is basically always detected in squamous cell carcinoma of the cervix and its precursors; a high incidence of HPV also has been reported in adenocarcinoma and adenocarcinoma in situ of the uterine cervix. Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci in 1999. It is difficult to differentiate minimal deviation adenocarcinoma (MDA) from LEGH preoperatively or postoperatively by clinical and pathologic features. The relationships between HPV and MDA or LEGH have not been studied well because of the rare incidence of the two diseases. To our knowledge, the HPV status in LEGH has not been reported. This study was designed to investigate HPV infection in MDA and LEGH, using the polymerase chain reaction (PCR) technique. Tumor tissue lesions were microdissected and the detection of HPV and its typing were analyzed by PCR-based assay. As the control, HPV DNA was detected in all cases of squamous cell carcinoma and three of five cases of adenocarcinoma. However, no HPV DNA was detected in any of the 10 cases of LEGH or in the 3 cases of MDA. These results suggest that MDA and LEGH are probably not related to HPV infection.

Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses.

We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.

Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum.

Wilms tumor gene (WT-1) expression has been reported in many human cancers, including most ovarian and peritoneal serous carcinomas, but has not been studied in carcinomas of the fallopian tube. In this study, the authors evaluated the immunohistochemical expression of WT-1 in serous carcinomas of the fallopian tube and compared their reactivity with that of ovarian, peritoneal, and endometrial serous carcinomas. All primary serous carcinomas of the fallopian tube (13 cases), ovaries (25 cases), and peritoneum (3 cases) were reactive with the WT-1 antibody, whereas all five primary endometrial serous carcinomas were nonreactive. WT-1 reactivity in an unknown primary serous carcinoma is therefore suggestive of an extrauterine site. The marked difference in WT-1 staining raises the possibility of genetic differences between serous carcinomas arising in the endometrium compared with those arising in the ovaries, fallopian tubes, and peritoneum.

Expression of the LIM proteins paxillin and Hic-5 in human tissues.

The LIM domain is a protein-protein interaction motif critically involved in a variety of fundamental biological processes, including cytoskeletal organization, cell lineage specification, and organ development. In this study we examined the expression of the LIM proteins paxillin and Hic-5 in adult human tissues by immunohistochemistry and immunoblotting. Paxillin expression was widespread and observed both in non-muscle and muscle tissues. Of the latter, paxillin was mainly expressed in multinuclear striated muscle. In contrast, Hic-5 showed restricted expression and was expressed in muscle tissues, mainly in mononuclear smooth muscle. Taken together with previous findings, it appears likely that the counterbalance between paxillin and Hic-5 may be deeply involved in muscle differentiation.