Clinicopathological features and programmed death-ligand 1 immunohistochemical expression in a multicenter cohort of uterine and ovarian melanomas: a retrospective study in Japan (KCOG-G1701s).

The objective of this study was to propose prognostic factors and optimal treatment strategies by analyzing the clinicopathological features and programmed death-ligand 1 (PD-L1) expression. We analyzed 31 patients diagnosed with uterine or ovarian melanoma between 1997 and 2017 in the Kansai Clinical Oncology Group/Intergroup. Twenty-four and seven patients with cervical and ovarian melanomas were included, respectively. Immune checkpoint inhibitors were used in seven patients, and the objective response rate was 40%. Notably, two patients with objective responses had a high PD-L1 expression. Ten and four patients with cervical and ovarian melanomas, respectively, had high PD-L1 immunohistochemical expressions. Multivariate analysis revealed that tumor stage was an independent prognostic factor for progression-free survival in patients with cervical melanomas. In patients with ovarian melanomas, the 1-year cumulative progression-free and overall survival rates were 0 and 29%, respectively. Kaplan-Meier analyses revealed that age <60 years was associated with poorer progression-free and overall survivals in patients with ovarian melanomas. In patients with cervical melanomas, the 1-, 3-, and 5-year cumulative overall survival rates were 53, 32, and 16%, respectively. Histological atypia was associated with a poorer progression-free survival, but there was no difference in survival between patients who underwent radical hysterectomy and those who did not. The present study is a large cohort study of uterine and ovarian melanomas, which are aggressive tumors with a significantly poor prognosis, even after standard surgery and adjuvant therapy. The use of immune checkpoint inhibitors is a promising and effective treatment option.

Possible involvement of loss of heterozygosity in malignant transformation of ovarian endometriosis.

OBJECTIVE: Although histological and epidemiological studies have suggested that endometriosis has malignant potential, the molecular mechanism underlying the malignant transformation of endometriosis is poorly understood. Ovarian cancer arising from endometriosis (OCEM) may provide an ideal model for genetic studies. To investigate the genetic alterations during transformation of ovarian endometriosis into cancer, we analysed loss of heterozygosity (LOH) and mutations of tumour-related genes in OCEM cases (n=12) that fulfilled the histological criteria and in solitary ovarian endometriosis (n=12). METHODS: Each paraffin-embedded section was microdissected to isolate the endometriotic epithelium, transitional epithelium, and cancer cells. Extracted DNA was amplified by nested PCR. LOH was identified with fluorescence-labelled microsatellite markers. Mutations of tumour-related genes PTEN, TP53, and K-ras were examined by bidirectional DNA sequencing. RESULTS: With 13 microsatellite markers on six chromosomes, we detected 31 and eight LOH events in OCEMs and in solitary ovarian endometriosis, respectively. In the OCEM group, 18 LOH events were found in cancer cells alone, while 13 LOH events were found in all cancer, transitional, and endometriotic tissues. High frequencies of LOH were detected on chromosomes 9p, 10q, and 13q. However, only two point mutations were detected in cancer cells in one case. CONCLUSION: Our study suggested that accumulated LOH events on some chromosome loci may be involved in malignant transformation of endometriosis, while mutations in certain tumour-related genes are not.

Adenocarcinoma in situ admixed with small cell neuroendocrine carcinoma of the cervix: A case report with cytological features.

Primary cervical small cell neuroendocrine carcinoma (SCNEC) is a rare and aggressive tumor. Herein, we describe the first cytological case of adenocarcinoma in situ (AIS) admixed with SCNEC. A 65-year-old postmenopausal Japanese female presented with abnormal genital bleeding. The Papanicolaou smear of the cervix demonstrated the presence of 2 distinct neoplastic components in an inflammatory background. One component consisted of aggregates of small round cells with a high nuclear/cytoplasmic ratio and round to oval nuclei with powdery chromatin, and inconspicuous nucleoli. Nuclear molding was characteristic. The other component consisted of irregular overlapping clusters of tall columnar cells with large round to oval nuclei containing coarse chromatin, and relatively rich cytoplasm. Accordingly, AIS admixed with SCNEC was suspected. Although the cytological features of cervical SCNEC are characteristic, the cytodiagnosis of this type of tumor may be difficult because of the rarity of the tumor. The presence of non-neuroendocrine tumor components in cervical SCNEC is not unusual, therefore careful observation is needed not to miss SCNEC components in the diagnosis of squamous cell carcinoma and/or adenocarcinoma in cervical cytological specimens.

[Phase II study of combination therapy with paclitaxel and carboplatin against postoperative small residual disease in patients with stage I c-IV ovarian cancer--KCOG 989 trial].

The tolerability and feasibility of combination therapy with paclitaxel (TXL) and carboplatin (CBDCA) against small residual disease following first-line optimal debulking of stage I c-IV ovarian cancer were evaluated in a multicenter dose-finding study. Eligibility criteria included histologically diagnosed stage I c-IV epithelial ovarian cancer with a postoperative residual lesion < or = 10 mm in diameter, no prior chemotherapy, and written informed consent of the patient and his/her family members to the chemotherapy. Twenty-two patients were enrolled and 20 of them were eligible. The patients were to receive 5 courses of TXL (175 mg/m2) and CBDCA (AUC 5) every 3 weeks. Hematological toxicities occurred in the form of grade 3 leukopenia during 25.7% of all courses, grade 3 neutropenia during 32.0% of all courses, and grade 4 neutropenia during 56.0% of all courses. No courses were associated with grade 4 leukopenia. G-CSF support was needed during 48 of 109 courses (44%) and caused normalization of the leukocyte count from a nadir of 1,921 +/- 434/mm3 after a mean time of 6 +/- 3.1 days, compared with 6 +/- 3.6 days needed for recovery from a nadir of 2, 357 +/- 360/mm3 without G-CSF support. This indicates similarly rapid recovery from severe leukopenia with the use of G-CSF. All eligible patients completed at least 5 courses of the chemotherapy. Some courses were given at a reduced dose or delayed due to toxicity but these dosage modifications were thought to be acceptable for both TXL and CBDCA. Five courses of TXL combined with CBDCA were tolerated well in this patient population.