Makiko Omori

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.

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.

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. Diagn. Cytopathol. 2016;44:430–433.

Dysregulation of CDK inhibitors and p53 in HPV-negative endocervical adenocarcinoma.

Human papillomavirus (HPV)-negative adenocarcinoma (AC) is a minor subset of endocervical cancer, but its pathogenesis has yet to be elucidated. This study investigated the clinicopathologic features of HPV-negative endocervical AC (n=14) in comparison with HPV-positive endocervical AC (n=30), and further studied aberrations of cell-cycle regulators. Expression patterns of cyclin-dependent kinase inhibitors (p16, p14, p27, and p21) and p53 were evaluated immunohistochemically, and nuclear high-risk HPV DNA signals were detected by in situ hybridization and polymerase chain reaction. Immunoexpression of p16, p14, p27, p21, and p53 were observed in 90%, 67%, 77%, 40%, and 20% of HPV-positive ACs, and in 0%, 0%, 29%, 14%, and 57% of HPV-negative ACs, respectively. A higher frequency of lymph node metastasis and worse prognosis were significantly associated with HPV-negative AC. Our findings suggest that alteration of cyclin-dependent kinase inhibitors and p53 status may contribute to carcinogenesis and the clinical behavior of HPV-negative AC of the uterine cervix.

Umbilical endometriosis with giant degenerated uterine leiomyomas: A case report.

Highlights • We present an unusual case of umbilical endometriosis and huge uterine leiomyomas with marked hydropic and cystic degeneration.• Although umbilical tumors are uncommon, the differential diagnosis should include umbilical endometriosis, particularly in reproductive-age women.• Umbilical endometriosis can be suspected from the clinical presentation, but the diagnosis should be confirmed with histological examination.

Successful neoadjuvant chemotherapy for large cell neuroendocrine carcinoma of the cervix: A case report

Highlights • We present a case of cervical large cell neuroendocrine carcinoma (LCNEC) and neoadjuvant chemotherapy with irinotecan plus cisplatin that was extremely effective.• Cervical LCNEC is uncommon and highly aggressive, and optimal therapy has yet to be determined.• This case suggests that neoadjuvant chemotherapy followed by radical hysterectomy could be a useful treatment option for bulky cervical LCNEC.

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. Diagn. Cytopathol. 2015;43:581–584.

Extraovarian Fibroma With Minor Sex Cord Elements: A Case Report and Literature Review

Extraovarian sex cord–stromal tumor is an exceedingly uncommon entity that may cause a diagnostic dilemma clinically. We report a case of extraovarian fibroma with minor sex cord elements arising in the left broad ligament. The patient was a 66-year-old woman presenting with an intra-abdominal solid mass near the left ovary on magnetic resonance imaging. The tumor was located in the left broad ligament in contact with the left ovary and fallopian tube based on laparotomy findings. Histological examination revealed that the tumor was a fibroma that contained cell nests with aggregates resembling the Call-Exner bodies of granulosa cell tumors and irregularly shaped cell nests composed of undifferentiated sex cord–type cells. Cellular atypia or mitotic figures were not identified in any of the components. It was speculated that the possible site of origin of this tumor might be a supernumerary ovary in the broad ligament that was thought to be derived from embryonic remnants.

MR-guided Focused Ultrasound for Uterine Fibroids: A Preliminary Study of Relationship between the Treatment Outcomes and Factors of MR Images Including Elastography

We evaluated the value of magnetic resonance elastography (MRE) for the prediction of response to magnetic resonance-guided focused ultrasound (MRgFUS) for uterine fibroids. Eleven patients were enrolled. A fractional change of >30% in Symptoms Severity Score (SSS) was defined as a ‘substantial symptomatic improvement’ at 12 months after treatment. The fractional stiffness value reduction in the patients with a substantial improvement in SSS was significantly higher than that in those without (P = 0.0446).

A case of endocervical minimal deviation adenocarcinoma with varicolored cytopathologic features on Pap smear

We report a case of minimal deviation adenocarcinoma (MDA) of the uterine cervix showing varicolored cytopathologic features on Papanicolaou (Pap) smear, which may indicate features suggestive of lobular endocervical glandular hyperplasia (LEGH)‐adenocarcinoma sequence. A 57‐year‐old woman presented with a profuse amount of watery vaginal discharge. Gynecological examination revealed a cervical mass with involvement of the right parametrium. Conventional Pap smear showed hypercellularity consisting of approximately 4 types of clusters as follows: (1) clusters showing a monolayered honeycomb sheet of endocervical cells with golden‐yellow mucin and bland nuclei, (2) three‐dimensional clusters showing varicolored mucin and irregular nuclear overlapping, (3) irregularly shaped clusters showing distorted chicken‐wire‐mesh appearance with noticeable protrusions of the nuclei and clear or faint varicolored cytoplasm, and (4) crowded clusters showing scarce mucin and nuclear atypia. The surgically resected uterus revealed LEGH‐mimicking lesion with fused papillae and a cribriform pattern in the endocervix and many glands exhibiting gastric differentiation that invaded deeper areas of the stroma with a subtle stromal reaction. Compared with histologic findings, two types of clusters, the crowded cluster with scarce mucin and the cluster with distorted chicken‐wire‐mesh‐type appearance, were considered as adenocarcinoma, and the latter was interpreted as a gastric‐type adenocarcinoma. Three‐dimensional varicolored type clusters showed atypical features, but insufficient atypical features compared with those of adenocarcinoma. Detection of clusters with varicolored mucin on conventional Pap smear may provide a clue for the early recognition of the malignant potential of LEGH on cytology. The chicken‐wire‐mesh type clusters may be a characteristic cytologic finding of MDA.