Development of Merkel Cell Carcinoma in a Patient Receiving Rituximab.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, and aggressive dermatological neoplasm. It is commonly reported in Caucasian ethnicities, and almost 50% of the patients have a concomitant malignancy and are on immunosuppressive chemotherapy. Here, we present a 79-year-old woman with a history of relapsed Stage II, grade III follicular lymphoma, receiving maintenance rituximab infusions. She presented with a raised erythematous papule on her left cheek. An excisional biopsy of the lesion confirmed a diagnosis of Merkel cell carcinoma. After which, she underwent a wider excision with 1-2 cm margins. PET scan did not reveal any FDG-avid uptake lesions that would be concerning for metastatic disease. However, she underwent a sentinel lymph node biopsy which was also negative. Thus, the diagnosis was finalized as Stage I (T1 N0 M0) MCC. There are only two reported cases in literature about the significant progression of Merkel cell carcinoma in patients who coincidentally were receiving rituximab as a part of treatment for another disease. This raises questions for future investigation and research on whether there is a direct association between rituximab use specifically and the rapid growth of MCC.

Therapeutic landscape of advanced HER2-positive breast cancer in 2022.

HER2-positive breast cancer is an aggressive subtype of breast cancer with five-year survival rates of 30% for the advanced stage. The development of anti-HER2 treatments has led to a paradigm shift in the management and clinical outcomes of advanced HER2-positive breast cancer patients. The standard first-line treatment consists of taxane-based chemotherapy plus dual anti-HER2 therapies with trastuzumab and pertuzumab. The antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) has been a second-line therapeutic standard, but the second-line treatment approach is rapidly evolving. Given a substantial advantage of another ADC, Fam-trastuzumab deruxtecan (T-DXd), compared to T-DM1 in a recent randomized trial in the second-line setting, T-DXd is currently the preferred second-line option. Optimal third-line treatment strategies are still not established, and multiple approaches have been used including combinations based on capecitabine, trastuzumab, or both with oral anti-HER2 tyrosine kinase inhibitors. Tucatinib plus capecitabine and trastuzumab, lapatinib plus trastuzumab, neratinib or lapatinib plus capecitabine are some of the FDA approved combinations. Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents.

Severe Thrombocytopenia Two Weeks Following Immunization with the Janssen Ad26.CoV2.S Vaccine.

Immune thrombocytopenia (ITP) has been associated with immunizations with various proposed mechanisms, including overactivation of the immune system and production of antibodies against circulating platelets. ITP has also been associated with several viral infections, including HCV, HIV, and most recently, active SARS-CoV-2 infection. Here, we present a case of a 52-year-old male with no past medical history who sought evaluation with his primary care physician for upper and lower extremity ecchymosis of one week duration. Outpatient laboratory studies were notable for severe isolated thrombocytopenia with platelet count of 8 × 10^9/L. Interestingly, he received the Johnson and Johnson COVID-19 vaccine 16 days prior to his presentation. Clinical work up and laboratory investigations led to the diagnosis of ITP.

NUT midline lung cancer: a rare case report with literature review.

Nuclear carcinoma of the testis (NUT) midline carcinoma are rare, poorly differentiated tumors resulting from t(15; 19) rearrangement, clinically characterized by aggressive and rapid progression to death. No optimal treatment regimen has been established for this rare malignancy. Surgery, chemotherapy, and radiation have been used for treatment alone or in combination, depending on location and staging of the disease, and may confer short periods of remission; however, re-emergence of the disease inevitably occurs. Targeted therapies such as bromodomain and extra-terminal domain protein (BET) inhibitors are currently in early phases of clinical trials. Here we describe a 49-year-old-male with no comorbidities who presented with acute worsening of chronic cough, new onset hemoptysis and left sided chest pain for 2 weeks. Workup revealed stage IIIB NUT midline carcinoma (NMC) of the lung with next-generation sequencing confirming the presence of a NUTM1-BRD4 fusion. The tumor was unresectable, and he began concurrent chemoradiation with weekly carboplatin and paclitaxel for 5 weeks. The follow-up CT scan showed partial response, so maintenance was continued with durvalumab. Two months later, he presented with metastasis to the posterior muscle compartment of the left arm, which was treated with local radiotherapy. Four months later he developed progression of lung disease with multiple pulmonary nodules. Durvalumab was discontinued and he was prescribed the BET inhibitor molibresib, 120 mg daily. After nearly 3 months of treatment with molibresib, he presented with brain metastasis for which he had a craniotomy with tumor resection and gamma knife radiation to solitary metastatic lesions. He was then prescribed chemo-immunotherapy with carboplatin plus pemetrexed and pembrolizumab. After two cycles of treatment his disease progressed, and he succumbed to it. Total survival was 18 months. In conclusion, NUT midline lung carcinoma is a rare but aggressive malignancy and patients have limited treatment options especially in advanced stages. Few targeted therapies have shown promising results in early clinical trials but more treatment options are awaited.