Context.— Gestational choriocarcinoma usually presents during the reproductive years, typically within 1 year of pregnancy, although presentation remote from pregnancy also occurs and may cause confusion with other tumors, including choriocarcinoma of germ cell origin and somatic carcinomas with choriocarcinomatous differentiation. It is important to separate these tumors for treatment and prognostic reasons. Objective.— To assess the utility of fluorescence in situ hybridization for the X and Y chromosome centromeres in determining the gestational origin of clinically ambiguous extrauterine choriocarcinomas in women. Design.— A review of female patients with extrauterine choriocarcinomas who had no evidence of prior gestational trophoblastic disease was performed. Samples were analyzed by fluorescence in situ hybridization for the X and Y chromosome centromeres using standard methodologies. Results.— Five cases met the criteria, all of which displayed trophoblastic cells and necrosis. Three cases (60%) had Y chromosomes by fluorescence in situ hybridization, which confirmed gestational origin. Although the 2 cases without a Y chromosome would ordinarily require molecular genotyping for paternal genetic material to establish gestational origin, in one of these cases a subsequent recurrence of yolk sac tumor allowed confirmation of its mediastinal origin. Conclusions.— Fluorescence in situ hybridization for detection of the X and Y chromosome centromeres is an effective screening test for gestational choriocarcinoma. It provided a definitive diagnosis of metastatic gestational choriocarcinoma in 3 of 5 potential cases that lacked a clinical history of gestational trophoblastic disease. An additional benefit is that more laboratories have the capability to perform fluorescence in situ hybridization than can perform molecular genotyping for definitive diagnosis.

Thymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, “testicular cancer”, embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.

TPS1105 Background: Patients (pts) with mTNBC have limited treatment options and poor prognosis. The combination of immune checkpoint inhibitors with chemotherapy shows promise, but only a subset of pts with mTNBC derive benefit, highlighting the need for new combinations. BEGONIA is an ongoing Simon 2-stage, multicenter, multi-arm platform study evaluating the safety and efficacy of D, an anti–PD-L1 monoclonal antibody, with or without P, in combination with novel oncology therapies as first-line treatment for mTNBC (NCT03742102). Dato-DXd is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (TROP2) IgG1 monoclonal antibody, a stable tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. Dato-DXd displayed encouraging clinical activity with a manageable safety profile in heavily pretreated pts with metastatic NSCLC in the phase 1 TROPION-PanTumor01 (NCT03401385) study. TROP2 is highly expressed on breast and other epithelial tumors, and a TROP2 ADC showed activity in heavily pretreated pts with mTNBC (Bardia, NEJM 2019). Methods: Eligible female pts are aged ≥18 years with untreated unresectable, locally advanced or mTNBC, ≥12 months since prior taxane therapy, ECOG PS 0/1, adequate organ function, and ≥1 nonirradiated measurable lesion. For Arm 7, pts are excluded if they have clinically significant corneal disease, history of interstitial lung disease/pneumonitis, underlying pulmonary disorder, or prior treatment with an ADC containing a topoisomerase I inhibitor. Arm 7 will evaluate D (1120 mg) + Dato-DXd (6 mg/kg) given intravenously every 3 weeks until disease progression or unacceptable toxicity. Part 1 of each arm includes a total of 30 pts with a safety run-in (n=6) to observe dose-limiting toxicities, identify the recommended phase 2 dose (RP2D), and detect an efficacy signal for part 1 expansion. The primary endpoint of part 1 is safety and tolerability. Secondary endpoints include investigator-assessed objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Once the RP2D has been established for part 1, a futility analysis will be performed with an option to expand the cohort to an additional 27 pts if expansion criteria are met. The primary endpoint for part 1 is ORR. Tumors will be assessed every 6 weeks per RECIST v1.1. Kaplan-Meier analysis will be used for PFS and OS. PD-L1 and TROP2 expression will be assessed by immunohistochemistry. Enrollment is ongoing. Clinical trial information: NCT03742102 .

A 25-year-old woman with systemic lupus erythematosus complicated by biventricular failure with a history of multiple admissions presented with cardiogenic shock unresponsive to steroids, intravenous immunoglobulin, cyclophosphamide, and required extra-corporeal membrane oxygenation. Left ventricular function eventually recovered after plasmapheresis. ( Level of Difficulty: Advanced. )

The human papillomavirus (HPV) status of squamous cell carcinomas (SCCs) of the head and neck is relevant for therapy planning, staging, and follow-up. Immunohistochemistry (IHC) for p16 is a surrogate marker of HPV status in oropharyngeal SCC, but not at other head and neck sites. We tested if the cobas HPV test was feasible and superior to p16-IHC on fine-needle aspiration (FNA) supernatants and frozen section (FS) scrapings of suspected SCC. A 500 μL aliquots of postcentrifugation supernatant CytoRich Red media of FNA cellblock specimens and scrapings of FS suspended in SurePath media vials were tested with the cobas HPV test and compared with p16-IHC and/or HPV in situ hybridization (ISH) performed on cellblock and/or resections. Twenty-nine (n=29) FNAs were tested for a cobas HPV test, p16, and/or HPV-ISH. The mean collection to testing time was 6.3 days (range: 0 to 24 d). Cobas yielded valid results in all cases; p16-IHC could not be interpreted in 4 (13%) cellblocks; correlation was performed on subsequent resections. Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FNA samples was 0.9, perfect agreement, sensitivity 100%, specificity 92.3%, positive predictive value 94.1%, negative predictive value 100%. Thirty-four (n=34) scrapings from FS were tested for cobas, p16, and/or HPV-ISH. The mean collection to testing time was 10.4 days (range: 1 to 28 d). Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FS scrapings was 1, perfect agreement. Sensitivity, specificity, positive predictive value, and negative predictive value was 100%. Cobas genotype was HPV-16 in 87%, HPV-18 in 3%, and HPV-other in 10%. Cobas HPV test in FNA supernatant and FS scrapings outperformed or was equivalent to p16-IHC and provided genotyping information.