The role of immunotherapy in treatment of brain metastases is unknown because most trials exclude patients with active brain lesions. As new immunomodulating agents gain approval for many malignancies, it is important to know if they have unique effects in the central nervous system (CNS). Here, we present a case of a patient with progressing brain metastases treated with a single cycle of pembrolizumab, who presented with mental status changes 11 days thereafter. MRI of the brain showed enlargement of CNS lesions with intense central enhancement and diffuse perilesional edema. Histologic evaluation of a resected lesion revealed isolated clusters of tumor cells surrounded by reactive astrocytosis, scattered inflammatory cells, and an abundance of microglial cells. Given the increasing use of immune checkpoint inhibitors in patients with brain metastases from melanoma and other diseases, recognition of pseudoprogression and management with immune suppression are essential.

TFI is a distinct neoplastic entity with a unique staining pattern and variable clinical presentation. One should be aware of the potential clinical presentation of multiple TFI as hypopigmented lesions especially in the head and neck area.

Background:Pancreatic masses may seldom represent a metastasis or secondary involvement by lymphoproliferative disorders. Recognition of this uncommon occurrence may help render an accurate diagnosis and avoid diagnostic pitfalls during endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). In this study, we review our experience in diagnosing secondary tumors involving the pancreas.Materials and Methods:The electronic database of cytopathology archives was searched for cases of secondary tumors involving the pancreas at our institution and a total of 31 cases were identified. The corresponding clinical presentations, imaging study findings, cytological diagnoses, the results of ancillary studies, and surgical follow-up, if available, were reviewed.Results:Nineteen of the patients were male and 12 female, with a mean age of 66 years. Twenty-three patients (74%) had a prior history of malignancy, with the latency ranging from 6 months to 19 years. The secondary tumors involving the pancreas included metastatic carcinoma (24 cases), metastatic sarcoma (3 cases), diffuse large B-cell lymphoma (2 cases), and plasma cell neoplasm (2 cases). The most common metastatic tumors were renal cell carcinoma (8 cases) and lung carcinoma (7 cases). Correct diagnoses were rendered in 29 cases (94%). The remaining two cases were misclassified as primary pancreatic carcinoma. In both cases, the patients had no known history of malignancy, and no ancillary studies were performed.Conclusions:Secondary tumors involving the pancreas can be accurately diagnosed by EUS-FNA. Recognizing uncommon cytomorphologic features, knowing prior history of malignancy, and performing ancillary studies are the keys to improve diagnostic performance and avoid diagnostic pitfalls.

Background PRAME (PReferentially expressed Antigen in Melanoma) immunohistochemistry has demonstrated high specificity for unequivocal melanomas; however, its utility in ambiguous melanocytic neoplasms has yet to be fully elucidated. Methods Cases of challenging melanocytic neoplasms were subclassified into one of three categories: challenging, favor benign (FB), challenging, cannot be subclassified (CCS), or challenging, favor malignant (FM). Using a previously published system, whereby cases with diffuse staining (>75%) were considered positive, scoring of PRAME was performed. Additionally, tumors with hotspot staining were also considered positive. Results Sixteen out of 85 tumors showed positive staining representing 5% of FB tumors, 24% of CCS tumors, and 47% of FM. In FB and CCS tumors, positive staining was mainly encountered in atypical intraepidermal melanocytic proliferations and spitzoid neoplasms. The specificity of positive PRAME staining was 95% and its concordance with the final diagnostic interpretation was 75%. Conclusions PRAME positivity is more common in neoplasms favored to be malignant by histopathologic evaluation. Its clinical utility may include early diagnosis of incipient melanoma in situ. Rarely, benign melanocytic neoplasms could show diffuse expression of PRAME, and additional studies are needed to determine optimal utilization. Lastly, hotspot staining may increase its sensitivity without much compromise in specificity.

Cutaneous syncytial myoepithelioma is a recently described rare tumor of the dermis. It is derived and composed purely of myoepithelial cells and shows a characteristic syncytial growth pattern of neoplastic cells with little intervening stroma and no recognizable ductal structures. It represents a diagnostic challenge to dermatopathologists given its rarity and unusual immunophenotype. Molecular testing for rearrangement of the EWSR1 gene plays a significant role in confirming the diagnosis in most cases. Herein, we present 2 cases with mundane clinical presentations and challenging histopathological findings. In both cases, the lesion was composed of relatively well‐circumscribed proliferation of epithelioid and spindle cells in the superficial dermis growing in a syncytial fashion and showing focal adipocytic metaplasia. The 2 cases had slightly different immunohistochemical profiles, but shared focal positivity for S100, EMA and pan‐keratin or p63. Break‐apart FISH demonstrated the presence of an EWSR1 gene rearrangement confirming the diagnosis in both cases. We discuss the most important differential diagnoses, particularly melanocytic lesions and epithelioid sarcoma and the original diagnostic considerations that the cases were referred to us with. We also review the molecular features and spectrum of immunohistochemical findings in these lesions and their role in excluding entities in the differential diagnosis.