Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements.

NTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18-53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2T>C, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged "prostatic stromal sarcoma," while substantiating CDKN2A deletion as a frequent occurrence.

A Comparative Study of Intraoperative Cytology and Frozen Sections of Sclerosing Pneumocytoma.

Sclerosing pneumocytoma (SP) is a rare benign neoplasm of the lung. Conservative surgical excision is curative with an excellent prognosis. Preoperative diagnosis of SP can be difficult. Thus, intraoperative frozen sections play a crucial role in guiding surgical management. However, the interpretation of frozen section can be challenging due to freezing artifact. Intraoperative cytology provides a complementary and better morphological detail. In this study, we review and compare the intraoperative cytology and frozen section of 14 cases of SP. SP is characterized by containing 2 cell types: round stromal cells and cuboidal surface cells. The round stromal cells were small with uniform nuclei and inconspicuous nucleoli. The cuboidal surface cells were more differentiated into type II pneumocytes and showed slightly larger in size with intranuclear inclusions. The immunocytochemical double-labeling staining could display 2 distinct population of vimentin-positive round stromal cells and cytokeratin 7-positive cuboidal surface cells. Recognition of the cytological features of SP circumvents the frozen section artifact and is a useful adjunct to the frozen section in leading to the correct diagnosis of SP.

Cytodiagnostic aspects of lung adenocarcinoma manifesting with micropapillary pattern in sputum: a case report of potential diagnostic pitfall.

The micropapillary pattern of lung adenocarcinoma was discussed in the 2004 World Health Organization classification and is now proposed as a distinct pattern in the new International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines. The micropapillary pattern is histologically characterized by papillary tufts lacking a central fibrovascular core and is associated with an unfavorable prognosis. Herein, we report the cytological features of lung adenocarcinoma with the micropapillary pattern in a sputum specimen. A 75-year-old woman presented with a productive cough, blood-tinged sputum, and some symptoms of upper respiratory tract infection. The initial impressions from her chest radiograph and computed tomography scan indicated pneumonia. However, the initial sputum cytology sample showed a few clusters of cells with abnormal three-dimensional structure, interpreted as adenocarcinoma. These cells were small and had minimal cytologic atypia, demonstrating a potential diagnostic pitfall. The following biopsy confirmed lung adenocarcinoma with the micropapillary pattern. Here, we describe this case and discuss the differential diagnosis of pulmonary entities exhibiting similar morphologies.

Langerhans Cell Sarcoma in a Chronic Myelogenous Leukemia Patient Undergoing Imatinib Mesylate Therapy: A Case Study and Review of the Literature.

Langerhans cell sarcoma (LCS) is a rare malignancy requiring differential diagnosis from other high-grade nonhematologic and hematologic tumors. The pathogenesis of LCS remains unknown. Notably, LCS and its benign counterpart, Langerhans cell histiocytosis (LCH), are frequently associated with other malignancies. To the best of our knowledge, we describe the first case of LCS in a chronic myelogenous leukemia (CML) patient undergoing imatinib mesylate therapy. We performed molecular cytogenetic analyses for investigating the association between LCS and CML. In our case, molecular cytogenetic analysis did not reveal BCR-ABL1 fusion and BRAF V600E mutation, suggesting that LCS may be coincident in this patient. However, recurrent BRAF V600E mutation has been found in LCH. Published reports have revealed the clonal relationship between LCH/LCS and other hematologic malignancies, especially lymphoid neoplasms. However, there are only 2 reports demonstrating the clonal relationship between LCH and myeloid neoplasms. The association of LCH/LCS with myeloid neoplasms and the role of BRAF V600E mutation in LCS are discussed.