FNA and effusion cytology of thoracic SMARCA4-deficient undifferentiated tumor and SMARCA4-deficient NSCLC
The literature has recently described thoracic switch/sucrose nonfermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4)-deficient (SD) malignancies, including SD undifferentiated tumor (SD-UT) and SD non-small cell lung carcinoma (SD-NSCLC). However, the cytologic features of these neoplasms in fine-needle aspiration (FNA) and effusion specimens have rarely been reported. The authors conducted a multicenter study in which they described and compared the spectrum of cytologic, immunohistochemical, and clinical features of these high-grade malignancies. The study documented clinical and imaging characteristics of tumors from 27 patients, which were retrieved from four institutions. Sixteen cytomorphologic features and IHC findings were compared between SD-UT and SD-NSCLC samples. Twenty-three FNAs, two bronchial brushings, and two pleural fluids were evaluated for 17 patients with SD-UT (mean age, 70 years) and 10 with SD-NSCLC (mean age, 62 years). Both types of malignancies presented with large thoracic masses or hilar/mediastinal lymphadenopathy, or both. All SD-UT cytologic samples had a discohesive or mixed cohesive–discohesive architecture, and most (13 of 17) showed predominant rhabdoid or mixed rhabdoid–epithelioid features. Most SD-NSCLC cytologic samples (nine of 10) were either cohesive or mixed cohesive–discohesive and had a predominantly epithelioid morphology (eight of 10). Keratins and claudin-4 were negative or focally positive in SD-UT samples and diffusely positive in SD-NSCLC samples. Both malignancies were negative for TTF-1 and p40/p63 and showed loss of expression of SMARCA4. The authors concluded that although there is considerable clinical and cytopathologic overlap between SD-UT and SD-NSCLC, each has its own distinct key features. SD-UT is mostly discohesive with rhabdoid or mixed rhabdoid–epithelioid features, whereas SD-NSCLC often has cohesive epithelioid morphology. The combination of clinical presentation, cytomorphology, and IHC is essential for a definitive diagnosis.
Zalles N, Mukhopadhyay S, Satturwar S, et al. Fine-needle aspiration and effusion cytology of thoracic SMARCA4–deficient undifferentiated tumor and SMARCA4-deficient non-small cell lung carcinoma: A multi-institutional experience with 27 patients. Cancer Cytopathol. 2024. doi.org/10.1002/cncy.22919
Correspondence: Dr. Tarik M. Elsheikh at [email protected]
Evaluation of assessment criteria for HER2 IHC in colorectal carcinoma
HER2 expression is an important biomarker for managing RAS wild-type metastatic colorectal carcinoma. IHC with reflex in situ hybridization (ISH) is a standard method of assessment, yet the criteria used to interpret results are from the HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) trial and MyPathway study. The HERACLES criteria require ISH confirmation when IHC staining is 3+ in 10 percent to 49 percent of cells, whereas the MyPathway criteria mirror those for gastric HER2 assessment and do not recommend ISH confirmation in the previously referenced scenario. The authors conducted a study to assess the prevalence of HER2 3+ heterogeneity and its association with ERBB2 copy number amplification to evaluate the necessity of ISH testing when IHC staining is 3+ in less than 50 percent of cells. Next-generation sequencing of DNA (592-gene panel or whole exome sequencing) was performed for 13,208 colorectal carcinoma (CRC) tumors submitted to Caris Life Sciences. HER2 (4B5) expression was tested using IHC. A subset of tumors was tested for ERBB2 amplification via chromogenic ISH or next-generation sequencing (copy number amplification), or both. Χ2 tests or Fisher exact tests were applied where appropriate, with probability values adjusted for multiple comparisons (P<.05). Of the 13,208 CRCs with HER2 IHC, 87.4 percent (11,541 of 13,208) were negative for HER2 expression (3+ or less intensity and less than 10 percent tumor cell staining) and 11.2 percent (1,473 of 13,208) demonstrated at least low HER2 expression (1 to 2+ and 10 percent or greater). Only 1.5 percent (194 of 13,208) of all tested tumors were positive or heterogeneously positive for HER2 overexpression (3+ and 10 percent or greater). Of these, 14 percent (28 of 194) had heterogenous HER2 overexpression (3+ staining of 10 percent to 49 percent of cells). Among 22 HER2-positive/heterogenous cases with successful ISH testing, 100 percent (22 of 22) demonstrated amplification via ISH. Because the classification of tumors as HER2 positive/heterogenous using IHC correlated very closely with ISH positivity, the results suggest that use of ISH is likely unnecessary for CRCs with 3+ HER2 overexpression in 10 percent to 49 percent of neoplastic cells.
Evans MG, Krause HB, Xiu J, et al. Evidence for unified assessment criteria of HER2 immunohistochemistry in colorectal carcinoma. Mod Pathol. 2024;38. doi.org/10.1016/j.modpat.2024.100654
Correspondence: Dr. Jaclyn F. Hechtman at [email protected]