Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma.

We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity. Flow cytometry (FCM) showed two distinct T-cell populations, CD4+ and CD8+ (+/- PD1), with no CD4/CD8 co-expression and no loss of panT-cell markers in either T-cell subset. FCM, accompanied by cell-sorting (CS), permitted the physical separation of four populations, as follows: CD4+/PD1-, CD4+/PD1+, CD8+/PD1- and CD8+/PD1+. TCR gene rearrangement studies on each of the four populations (by next generation sequencing, NGS) showed that the neoplastic population was of T-cytotoxic cell lineage. IHC showed the CD8+ population to be TIA-1+, but perforin- and granzyme-negative. Moreover, histiocytic markers did not render the peculiar staining pattern, which is characteristic of acral CD8+ T-cell lymphoma (PCACD8). Compared to the entities described in the 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas, we found that the indolent lymphoma described herein differed from all of them. We submit that this case represents a hitherto-undescribed type of CTCL.

Surgical Management and Contralateral Breast Cancer Risk in Women with History of Radiation Therapy for Hodgkin Lymphoma: Results from a Population-Based Cohort.

BACKGROUND: Women with history of chest irradiation for Hodgkin lymphoma are at increased risk of developing bilateral breast cancer, although contralateral breast cancer risk estimates in this population remain undefined. METHODS: We queried the SEER database for women treated with radiation therapy for Hodgkin lymphoma prior to age 30 years and were diagnosed with a subsequent breast cancer between 1990-2016. Trends in surgical management and the 5- and 10-year cumulative incidence of contralateral breast cancer were evaluated. RESULTS: The cohort included 295 women with a median age of 22 years (range 8-30 years) at Hodgkin lymphoma diagnosis, and 42 years (range 22-65 years) at breast cancer diagnosis. Overall, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Breast-conserving surgery was performed in 17.3% of patients, while mastectomy was performed in 82.7%. In 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent breast-conserving surgery and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients demonstrated a 40.5% bilateral mastectomy rate. The 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% [95% confidence interval (CI), 5.6-15.4%], increasing to 20.2% (95% CI, 13.7-29.2%) at 10-year and 29.9% (95% CI, 20.8-41.9%) at 15-year follow-up. CONCLUSIONS: Women with a history of prior chest radiation for Hodgkin lymphoma with a diagnosis of breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making for management of this high-risk patient population.

B-cell cytopenia and time to last B-cell-depleting therapy predict response to SARS-COV-2 vaccines in patients with lymphoproliferative disorders.

Patients with B-non-Hodgkin lymphoma (NHL) are at increased risk of morbidity and mortality from SARS-CoV-2. We investigated the relationship between B cell cytopenia and the SARS-CoV-2 vaccine response in B-NHL patients. We measured anti-RBD antibodies and the lymphocyte immunophenotype in 19 controls, 22 lymphoma patients on observation (cohort 1) and 55 lymphoma patients receiving their vaccines post B-cell depleting therapy (cohort 2). Half of the lymphoma patients in both cohorts achieved seropositivity compared to 100% of controls. In cohort 2, only 5% achieved an antibody response in the first year post B-cell depleting treatment, vs 88% treated >2 years prior. Also, 28% of patients with <50 B cells/µl achieved a serologic response vs 86% of patients with B-cell >50 B cells/µl. B-cell cytopenia is profound within the first year of exposure to B-cell depleting treatment, therefore an additional dose of vaccine within that timeframe is unlikely to raise antibody levels.

Clinicopathologic features of breast cancers diagnosed in women treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.

BACKGROUND: Childhood and young adult survivors of Hodgkin lymphoma (HL) are at elevated risk of developing breast cancer, yet little data exist on the tumor characteristics that develop in this high-risk patient population. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify breast cancers diagnosed between 1990 and 2016 in women who had received prior radiation therapy for HL at age 30 years or younger. Clinicopathologic features of subsequent breast cancers (breast cancer after radiation therapy for HL [BC-HL]) were examined and compared with breast cancers diagnosed in women who had no prior malignancy (breast cancer with no prior malignancy [BC-NPM]). RESULTS: In total, 321 breast cancers were identified in 257 women who had a history of radiation therapy for HL. The median age at HL diagnosis was 22 years (interquartile range, 18-26 years), and nearly all patients in the BC-HL group (97.9%) were diagnosed ≥8 years after radiation therapy. Overall, 56 patients in the BC-HL group (21.8%) developed bilateral breast cancer. Compared with women who had BC-NPM, those who had BC-HL were younger (43 vs 60 years; P < .001) and were less likely to present with ductal carcinoma in situ (8.4% vs 14.9%; P = .001). On multivariable analysis that included adjustment for age, invasive BC-HL was associated with smaller (≤2 cm) tumor size (odds ratio, 1.64; 95% CI, 1.25-2.15) and upper outer quadrant tumors (odds ratio, 1.37; 95% CI, 1.04-1.81) compared with BC-NPM. In a subset analysis of 102 women who had HER2/neu status available, the distribution of biologic subtype was not significantly different between BC-HL and BC-NPM (P = .16). CONCLUSIONS: Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation. LAY SUMMARY: Women who have had radiation therapy for Hodgkin lymphoma at a young age are at increased risk of developing early onset breast cancer; however, most of these breast cancers are sensitive to hormones (estrogen receptor-positive) and are diagnosed at early stages. Because these breast tumors are estrogen receptor-positive, medications that prevent breast cancer by blocking the effect of or lowering hormone levels (also termed endocrine prevention) may be useful in this group of high-risk women.