A 57-year-old man with rapidly progressive pulmonary hypertension.

Pulmonary Tumor Thrombotic Microangiopathy (PTTM) is a rare condition associated with neoplastic disorders, predominantly gastric cancer, leading to pre-capillary Pulmonary Hypertension (PH). The pathologic mechanism involved is a fibrocellular intimal proliferation of small pulmonary vessels sustained by nests of carcinomatous cells lodged in pulmonary vasculature. Clinical presentation is nonspecific, including progressive dyspnea and dry cough. Diagnosis of PTTM is extremely challenging ante-mortem and prognosis is poor. Here we describe the case of a middle-aged man, without known previous cancer history. The clinical course was rapidly unfavorable, with progressive dyspnea and PH associated with hemodynamic instability, eventually culminating in patient's death. PTTM diagnosis was made post-mortem. PTTM should be considered in any patient presenting with unexplained PH, especially if it is rapidly progressive, poorly responsive to standard approaches or there is suspected history of malignancy. A prompt diagnosis of PTTM could help in bringing light into this still under-recognized condition.

Streamlining genetic testing for women with ovarian cancer in a Northern California health care system.

OBJECTIVE: Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing. METHODS: A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system. RESULTS: Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process. CONCLUSION: Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.

Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma.

OBJECTIVE: Thalidomide is an anti-angiogenesis agent that has shown activity in some solid tumors. We performed a phase I clinical trial to determine the toxicity and potential efficacy of Thalidomide in recurrent epithelial ovarian carcinoma. METHODS: Patients with recurrent ovarian cancer were evaluated between 1998 and 2000. Data were evaluated using Kaplan-Meier and logistic regression analyses. RESULTS: 17 heavily pretreated patients with recurrent epithelial ovarian cancer received oral Thalidomide starting at 100 mg/day, with dose escalations of 100 mg/day every 2 weeks, up to 1200 mg/day as tolerated. The median number of courses was four (range: 1-18 courses), and median dose was 200 mg/day (range: 100-600 mg/day). Treatment duration ranged from 2 to 48 months. Common grade 1 or 2 side effects included constipation (76%), neuropathy (71%), and fatigue (65%) with few grade 3 or 4 events. Three (18%) patients had partial responses, and six (35%) had stabilization of disease after 6 months. After 1 year of treatment, six of the nine patients with an initial partial response (n=2) or stable disease (n=4) remained in these response categories. Median time to progression was 10 months. Forty-seven percent of patients had a 50-70% decrease in CA125 levels. Using logistic regression and repeated measures analyses, CA125 levels decreased by 62 units/ml per month (p=0.07). CONCLUSION: Our study demonstrates the safety, tolerability, and potential efficacy of Thalidomide in recurrent and refractory epithelial ovarian cancers. Additional clinical trials are warranted.

Microinvasive Paget's disease.

BACKGROUND: Microinvasive squamous cell carcinoma of the vulva is defined as stromal invasion < or =1 mm and is treated by wide local resection. Whether criteria for microinvasive squamous cell carcinoma can be applied to Paget's disease of the vulva is unknown because of the rarity of that disease. CASES: We initially evaluated three cases of microinvasive Paget's disease by using sentinel lymph node (SLN) analysis. The SLNs in two patients were negative; and these patients had no recurrence of invasive or metastatic Paget's disease. The other patient had a positive SLN (the only positive lymph node) and subsequently received complete lymph node dissection of the groin bilaterally. CONCLUSION: Evaluation of SLNs may be valid for evaluating microinvasive Paget's disease.

Gene expression patterns in ovarian carcinomas.

We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers.

Liposomal doxorubicin for treatment of metastatic chemorefractory vulvar adenocarcinoma.

BACKGROUND: Primaryadenocarcinoma of the vulva is a rare entity, and for widely metastatic vulvar adenocarcinoma, no effective treatment has been established. CASE: A 65-year-old woman was diagnosed with regionally advanced vulvar adenocarcinoma, with bulky involvement of bilateral groin lymph nodes, and associated extramammary Paget's disease. Initial therapy consisted of multiagent chemotherapy and vulvar and groin irradiation, followed by radical vulvectomy with groin and pelvic lymph node dissection. She subsequently developed widely metastatic disease including brain, pulmonary, hepatic, osseus, and subcutaneous lesions. Treatment with liposomal doxorubicin (Doxil) resulted in dramatic regression of metastatic lesions and marked improvement in quality-of-life. She remains clinically well, greater than 1 year since initiating Doxil treatment for widely metastatic vulvar adenocarcinoma, and has surpassed 5 years of survival since her initial diagnosis. CONCLUSIONS: We report the first case of Doxil used for the treatment of metastatic chemorefractory vulvar adenocarcinoma. We observed that Doxil was a well-tolerated and effective agent for this gynecologic malignancy, and warrants further investigation.