Immunotherapy in synchronous MSI-H rectal adenocarcinoma and upper tract urothelial carcinoma: a case report.

Background: A growing body of evidence suggests that conventional chemotherapy may not be effective in mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC). Alternative strategies, such as immunotherapy, are currently being investigated both in the neoadjuvant and adjuvant setting. Furthermore, immunotherapy is an attractive alternative to the use of combination chemotherapy regimens when treating synchronous primary cancers such as in the setting of inherited cancer syndromes. Case Description: Here we present a case of a middle-aged woman diagnosed with dMMR/MSI-H locally advanced rectal cancer with synchronous upper tract urothelial cancer secondary to Lynch syndrome. The patient was first treated using neoadjuvant chemotherapy followed by chemoradiation, resulting in only a partial pathologic response. Following surgery, the patient was treated with adjuvant combination immunotherapy with nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, resulting in a durable disease-free interval of nearly 21 months. Conclusions: This case report illustrates the importance of determining dMMR/MSI-H status in LARC and the consideration of immunotherapy (particularly with synchronous primaries as seen in inherited cancer syndromes), reviews the current literature, and calls for further investigation into the use of neoadjuvant and adjuvant immunotherapy in locally advanced rectal cancer along with upper tract urothelial carcinoma (UTUC).

Bone Mineral Density at the Time of Initiating Aromatase Inhibitor Therapy Is Associated With Decreased Fractures in Women With Breast Cancer.

Women with estrogen receptor-positive breast cancer who receive an aromatase inhibitor (AI) are at risk for fractures. We aim to determine if dual-energy X-ray absorptiometry (DXA) scans made at the time of AI initiation are associated with decreased fractures. We retrospectively identified 25,158 women with local or regional breast cancer diagnosed between 2005 and 2013 who received AI therapy between 2007 and 2013 from the Medicare-linked Surveillance, Epidemiology, and End Results Program and Texas Cancer Registry databases. We defined baseline DXA screening using claims made between 1 year before and 6 months after each patient's first AI claim to examine determinants of baseline screening using a multivariable GENMOD model. We included a propensity score adjustment in Cox proportional hazard models to assess the association between time-varying DXA screening and the risk of fractures. Additionally, we compared the use of antiresorptive therapy drugs between the two groups. Of the study cohort, 14,738 (58.6%) received DXA screening. The screening rates increased annually from 52.1% in 2007 to 61.7% in 2013. Higher screening rates were observed in patients with younger age, married status, non-Hispanic white race, localized disease, fewer comorbidities, more than one type of aromatase inhibitor drug claim, no state buy-in (surrogate for low socioeconomic status), higher education level, and prior osteoporosis diagnosis. Baseline DXA screening was associated with decreased risk of subsequent fractures (hazard ratio = 0.91; 95% confidence interval, 0.86-0.97, p < .001) after multivariable and propensity score adjustment. Bone-modifying drugs were prescribed to 4440 (30.1%) patients with screening compared with 1766 (16.9%) without (p < .001). Of the 4440 patients who received treatment, 95% received bisphosphonates. Our study demonstrated baseline DXA screening was associated with a decreased risk of fractures and a higher likelihood of receiving antiresorptive therapies. Improvement of the baseline DXA screening is still needed in practice. © 2021 American Society for Bone and Mineral Research (ASBMR).

A Case of Chemotherapy-Refractory "THRLBCL like Transformation of NLPHL" Successfully Treated with Lenalidomide.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of nonclassical Hodgkin lymphoma (HL). It resembles non-Hodgkin lymphoma (NHL), by expressing classic B cell markers such as CD20 and CD79a however lacks definitive HL markers (such as CD15 and CD30). T cell histiocyte-rich large B cell lymphoma (THRLBCL), on the other hand, is a distinct entity classified under NHL and considered a variant of diffuse large B cell lymphoma (DLBCL). NLPHL can look morphologically and immunologically similar to THRLBCL and often poses a diagnostic challenge. Neoplastic cells in both NLPHL and THRLBCL express B cell markers and are typically scattered in a background of reactive cells. The two major differences are the background cell type and the morphologic pattern. Despite having a phenotypic resemblance, they have distinct biologic behavior and clinical course. NLPHL typically has an indolent course, and THRLBCL has an aggressive course. Hence, differentiating these two entities is critical not only for prognosis but for treatment purposes. Of note, NLPHL has a small risk of transformation to an aggressive lymphoma such as THRLBCL.

Thymic carcinoma presenting as disseminated intravascular coagulation.

Thymomas and thymic carcinomas are rare tumors, which originate from the epithelial cells of the thymus. We present a case of thymic carcinoma, which presented with DIC as an initial manifestation. DIC improved with corticosteroid treatment and thymic carcinoma was amendable to chemoradiation.