Unforeseen Complications of Pembrolizumab in Breast Reconstruction Post-Mastectomy.

A 53-year-old post-menopausal Indian female presented with invasive ductal carcinoma, treated with neoadjuvant chemotherapy and pembrolizumab due to a PD-L1 combined positive score of 5. Following a right mastectomy and axillary dissection, she received a breast expander and AlloDerm™ graft. After resuming pembrolizumab and paclitaxel postoperatively, she developed severe breast redness and high-grade fever, necessitating expander removal due to suspected pembrolizumab-induced complications. This case underscores the unique and severe adverse effects of pembrolizumab on breast reconstruction, highlighting the need for careful monitoring and management in patients undergoing similar treatments. LEARNING POINTS: Among patients with early triple-negative breast cancer, the combination of pembrolizumab with neoadjuvant chemotherapy enhances outcomes compared to chemotherapy alone.Early recognition is essential for managing pembrolizumab-induced complications, as demonstrated by the need for expander removal and debridement in this case.The unique adverse effects observed in this case underscore the importance of tailoring cancer treatment plans to individual patients, taking into account the potential risks associated with immunotherapy in the context of reconstructive surgery.

Unraveling the Mystery of Gray Zone Lymphoma in Human Immunodeficiency Virus-Seropositive Patients: Two Cases.

Gray zone lymphoma (GZL) is an uncommon neoplasm with intermediate features of both classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). It was identified in the World Health Organization (WHO) classification as its own neoplasm in 2008. Patients infected with human immunodeficiency virus (HIV) have been rarely diagnosed with this type of lymphoma and treatment strategies for this subset of patients is not well described. Here we present two cases of patients with HIV that were diagnosed with GZL in a single community-based institution. A 68-year-old male with HIV/acquired immunodeficiency syndrome (AIDS) on highly active antiretroviral therapy (HAART) presented with 6-month history of dyspnea and weight loss. Computed tomography (CT) of the chest revealed multiple lung and mediastinal lesions, the largest measuring 9.4 × 5.5 cm lesion in the right perihilar region. Lymph node biopsy revealed abnormal lymphocytes with immunohistochemistry (IHC) positive for cluster of differentiation 30 (CD30), CD20 and Epstein-Barr virus (EBV), consistent with a diagnosis of GZL. The patient received dose-adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and rituximab (DA-EPOCH-R) and attained a complete response. He since completed maintenance rituximab therapy and remains disease-free at 33 months. A 40-year-old female with HIV/AIDS on HAART presented with high-grade fever, dyspnea, and weight loss. CT imaging revealed multiple lung lesions, hepatosplenomegaly and diffuse lymphadenopathy in the chest and abdomen. Lymph node and bone marrow biopsy revealed cells positive for CD20, CD30, and EBV within atypical lymphoid cells. With this, a diagnosis of GZL was made and she was treated with DA-EPOCH-R. She attained a complete response and was on maintenance rituximab therapy. At 9 months she relapsed, she has now received a bone marrow transplant. GZL is a rarely described neoplasm within the HIV population. Here we describe two HIV patients diagnosed with GZL that were successfully treated at our institution. DA-EPOCH-R was able to induce durable remission with limited side effects and it represents a viable strategy for treating patients in this population. Further studies need to be performed to better characterize this lymphoma, especially in HIV patients. Treatment strategies for this select group of patients also need to be better defined.

A case of mantle cell lymphoma presenting with ascites.

Ascites with the finding of peritoneal carcinomatosis is considered an unusual presentation for mantle cell lymphoma (MCL) and has been rarely described in literature. This case reflects the importance of cytological analysis of peritoneal fluid in a patient with intractable ascites not contributing from other comorbidities. In the event a bone marrow (BM) analysis cannot be made, this may serve as an alternative method for diagnosing MCL taking into consideration the good concordance between peritoneal fluid and BM cytological markers.

Hemophagocytic lymphohistiocytosis in a patient with Goodpasture's syndrome: a rare clinical association.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome. HLH can occur in the setting of an autoimmune disease, chronic immunosuppression, malignancy, and infection. We discuss a rare case of a young woman who was diagnosed with Goodpasture's syndrome that was most likely complicated by HLH. To the best of our knowledge, this is the first report of HLH in the setting of this rare autoimmune disease. CASE REPORT: A 31-year-old woman who was diagnosed with Goodpasture's syndrome 7 years prior presented with febrile neutropenia. She was initially receiving treatment with azathioprine and prednisone, which was subsequently switched to hydroxychloroquine. Over time, she had developed polyarthritis and was later diagnosed with MPO-ANCA-positive vasculitides. On this admission, her clinical status deteriorated from persistent pancytopenia. This was initially attributed to the immunosuppressive effect of hydroxychloroquine. A bone marrow biopsy was performed and revealed hypercellular bone marrow without any cytogenetic abnormalities. Due to a prolonged pancytopenia thought to be of autoimmune etiology, treatment with high-dose steroids was initiated. With the persistent febrile episodes, hepatosplenomegaly on examination, and laboratory workup that revealed hyperferritinemia and pancytopenia, HLH syndrome was suspected. A repeat bone marrow biopsy confirmed this diagnosis with the presence of hemophagocytosis, demonstrated by the presence of histiocytes engulfing erythroid cells. She also met 5 of 8 diagnostic criteria, which confirmed the diagnosis of HLH. The patient eventually died despite aggressive treatment with high-dose steroid therapy for her autoimmune disorder, as well intravenous antibiotics and supportive care for her underlying infections. CONCLUSIONS: HLH is a syndrome marked by a hyper-inflammatory state aggravated by specific triggers. To make the diagnosis of HLH, at least 5 of the 8 criteria must be met. Treatment involves suppression of the overwhelming inflammatory response by the use of immunomodulators. The mortality rate can range from 50-90% due to delayed recognition and onset of treatment. Here, we present a rare case of Goodpasture's syndrome with overlap and pauci-immune vasculitis, which may have triggered the HLH. This correlation has not been described before in the literature.

Single cell network profiling assay in bladder cancer.

The aim of this study was to assess the feasibility of applying the single cell network profiling (SCNP) assay to the examination of signaling networks in epithelial cancer cells, using bladder washings from 29 bladder cancer (BC) and 15 nonbladder cancer (NC) subjects. This report describes the methods we developed to detect rare epithelial cells (within the cells we collected from bladder washings), distinguish cancer cells from normal epithelial cells, and reproducibly quantify signaling within these low frequency cancer cells. Specifically, antibodies against CD45, cytokeratin, EpCAM, and cleaved-PARP (cPARP) were used to differentiate nonapoptotic epithelial cells from leukocytes, while measurements of DNA content to determine aneuploidy (DAPI stain) allowed for distinction between tumor and normal epithelial cells. Signaling activity in the PI3K and MAPK pathways was assessed by measuring intracellular levels of p-AKT and p-ERK at baseline and in response to pathway modulation; 66% (N = 19) of BC samples and 27% (N = 4) of NC samples met the "evaluable" criteria, i.e., at least 400,000 total cells available upon sample receipt with >2% of cells showing an epithelial phenotype. The majority of epithelial cells detected in BC samples were nonapoptotic and all signaling data were generated from identified cPARP negative cells. In four of 19 BC samples but in none of the NC specimens, SCNP assay identified epithelial cancer cells with a quantifiable increase in epidermal growth factor-induced p-AKT and p-ERK levels. Furthermore, preincubation with the PI3K inhibitor GDC-0941 reduced or completely inhibited basal and epidermal growth factor-induced p-AKT but, as expected, had no effect on p-ERK levels. This study demonstrates the feasibility of applying SCNP assay using multiparametric flow cytometry to the functional characterization of rare, bladder cancer cells collected from bladder washing. Following assay standardization, this method could potentially serve as a tool for disease characterization and drug development in bladder cancer and other solid tumors.