Diffuse large B-cell lymphoma involving osseous sites: utility of response assessment by PET/CT and good longterm outcomes.

Osseous involvement by diffuse large B-cell lymphoma (DLBCL-bone) is a heterogeneous disease. There is limited data regarding response assessment by positron emission tomography with fluorodeoxyglucose, which may demonstrate residual avidity despite a complete response. We analyzed clinical data of patients with newly diagnosed DLBCL and identified all cases with DLBCL-bone. End of treatment scans were reviewed by two independent experts classifying osseous lesions into Deauville (DV) ≤3; DV ≥4, or reactive uptake in the bone marrow (M), site of fracture (F) or surgery (S). We compared outcomes of DLBCL-bone to other extranodal sites (EN) matched on International Prognotic Index features and regimen. Of 1,860 patients with DLBCL (bone 16%; EN 45%; nodal 39%), 41% had localized disease and 59% advanced. Only 9% (n=27) of patients with initial bone involvement had residual fluorodeoxyglucose avidity at the osseous site. In half of these cases, the uptake was attributed to F/S/M, and of the remaining 13, only two were truly refractory (both with persistent disease at other sites). Overall survival and progression-free survival (PFS) were found to be similar for early- stage nodal DLBCL and DLBCL-bone, but inferior in EN-DLBCL. Advanced-stage disease involving the bone had a similar 5-year PFS to nodal disease and EN-DLBCL. After matching for International Prognotic Index and treatment regiments, PFS between bone and other EN sites was similar. Osseous involvement in DLBCL does not portend a worse prognosis. End of treatment DV ≥4 can be expected in 5-10% of cases, but in the absence of other signs of refractory disease, may be followed expectantly.

A tale of two vulvar angiomyxomas: Two cases and review of literature.

Vulvar angiomyxomas are rare benign mesenchymal neoplasms. Superficial and Aggressive angiomyxomas are two distinct phenotypes that present similarly to other more common vulva-perineal pathologies. Albeit both angiomyxomas carry a risk of recurrence, especially in the setting of incomplete resection, simple excision is insufficient for Aggressive angiomyxoma. It requires wide local excision because of its unique potential for local invasion, infiltration of the paravaginal and pararectal tissue, and more distant metastasis. Here, we present a case of Superficial angiomyxoma and a case of Aggressive angiomyxoma to highlight the diagnostic challenges and management strategies of each tumor. In both cases, angiomyxomas were initially misdiagnosed because of their rarity and nonspecific presentation. Magnetic resonance imaging is the modality of choice for evaluation due to inherent higher spatial resolution of soft tissue anatomical details. Early diagnosis of Aggressive angiomyxoma can prevent incomplete excision and recurrence, spare additional surgery, and offer hormonal therapy options.

Shared decision making for patients with breast and gynecologic malignancies undergoing chemotherapy associated with persistent alopecia.

Objective: To assess patient-perceived involvement in shared decision making among those diagnosed with breast or gynecologic malignancies undergoing chemotherapy associated with persistent chemotherapy-induced alopecia (pCIA). We also sought to identify factors that influence shared decision making. Methods: We recruited patients from the Gynecologic Medical Oncology and Breast Medicine Services at a large academic center for this prospective cohort study. All patients were scheduled to start chemotherapy between June 1, 2017 and December 31, 2017. Following medical consultation, including discussion of the risk of pCIA, patients completed the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Clinical and sociodemographic information was also collected. Univariate analysis was used to evaluate SDM-Q-9 total scores and their constituents for all variables. Results: Sixty-one patients completed the survey. The median total SDM-Q-9 score was 95.6 (95% CI: 90-100). Most patients (n = 57, 93%) reported a high level of involvement (SDM-Q-9 total score > 66). There was no difference in total scores between patients with breast compared with gynecologic cancer (P > .05). By individual item, the scores for item Q1 ("My doctor made clear that a decision needs to be made") were significantly lower for Black patients and those with advanced disease (P < .05). Conclusions: Most patients indicated they were adequately involved in shared decision making regarding chemotherapy treatment options and their risk for pCIA. Patients from underrepresented populations and those with advanced disease may benefit from additional support from their clinicians to better address the anticipated psychosocial impacts of pCIA and facilitate the provision of optimal and equitable care.

Immunotherapy for recurrent or metastatic vulvar carcinoma: A case report and review of current guidelines.

There are limited treatment options for patients with advanced vulvar cancer. However, several immune checkpoint inhibitors (ICIs) are FDA-approved or NCCN-Compendia-listed for qualified patients with advanced disease. In this case report, we present a patient with metastatic vulvar squamous cell carcinoma who was treated with pembrolizumab in the setting of disease progression following prior treatment with radiation and chemotherapy. Best response to immunotherapy was an unconfirmed partial response. We summarize the current role of ICIs in treating advanced vulvar cancer, which is largely extrapolated from the squamous cell skin cancer and cervical cancer guidelines. Additionally, we emphasize the need for more inclusive clinical trials and a better understanding of vulvar cancer molecular biology, as well as the identification of biomarkers to predict response to targeted therapy in patients with advanced vulvar cancer.

Baseline risk of hematologic malignancy at initiation of frontline PARP inhibitor maintenance for BRCA1/2-associated ovarian cancer.

Poly(ADP-ribose) polymerase inhibitors (PARPi) are FDA approved as frontline maintenance for BRCA-associated advanced stage high-grade ovarian cancer (HGOC), having demonstrated an unprecedented improvement in relapse-free survival. Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are rare toxicities of PARPi. We describe three patients with germline BRCA-associated (gBRCA+) HGOC and alterations in AML driver genes. Although none evidenced overt hematologic malignancy, PARPi maintenance was cautiously considered given the potential risk of MDS/AML. A better understanding of the role of clonal hematopoiesis in the subsequent development of PARPi-associated MDS/AML will improve management of this patient population.

Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation.

Transcriptional regulators, including the cohesin complex member STAG2, are recurrently mutated in cancer. The role of STAG2 in gene regulation, hematopoiesis, and tumor suppression remains unresolved. We show that Stag2 deletion in hematopoietic stem and progenitor cells (HSPCs) results in altered hematopoietic function, increased self-renewal, and impaired differentiation. Chromatin immunoprecipitation (ChIP) sequencing revealed that, although Stag2 and Stag1 bind a shared set of genomic loci, a component of Stag2 binding sites is unoccupied by Stag1, even in Stag2-deficient HSPCs. Although concurrent loss of Stag2 and Stag1 abrogated hematopoiesis, Stag2 loss alone decreased chromatin accessibility and transcription of lineage-specification genes, including Ebf1 and Pax5, leading to increased self-renewal and reduced HSPC commitment to the B cell lineage. Our data illustrate a role for Stag2 in transformation and transcriptional dysregulation distinct from its shared role with Stag1 in chromosomal segregation.