Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a recently recognized eosinophilic renal neoplasm characterized by distinctive morphologic, immunophenotypic, and molecular features, including frequent TSC/mTOR pathway alterations. Recently, L1 cell adhesion molecule (L1CAM) has gained increasing recognition as a diagnostically and biologically relevant marker in selected eosinophilic renal neoplasms; however, its expression profile in ESC-RCC has not been systematically investigated. We aimed to evaluate L1CAM expression in a multicenter cohort of ESC-RCCs and correlate the findings with clinicopathologic and immunophenotypic features. A retrospective multicenter cohort of 11 ESC-RCCs was collected. Clinicopathologic and immunophenotypic findings were recorded. Immunohistochemistry for L1CAM was performed on representative whole tissue sections and semi-quantitatively scored based on the percentage of positive tumor cells. The cohort included 9 female and 2 male patients with a median age of 50 years (range, 39-79). L1CAM expression was identified in 7 of 11 tumors (63.6%), including 5 cases with diffuse membranous (3+) staining and 2 cases with intermediate (2+) staining; no tumor showed only focal (1+) expression. All tumors showed the characteristic morphology of ESC-RCC and expressed KRT20, irrespective of L1CAM status. Among tumors evaluated with additional markers, SDHB expression was retained in all 6 tested tumors and GATA3 was negative in all 5 tested tumors. Molecular testing was not performed in this cohort. Follow-up was available for all 11 patients (median, 10 months), with all patients alive without disease at last follow-up. Our findings expand the known immunophenotypic spectrum of ESC-RCC by demonstrating L1CAM expression in a substantial subset of tumors. However, because L1CAM expression is neither sensitive nor specific for ESC-RCC, positive or negative staining does not support or exclude the diagnosis and does not currently justify routine use of L1CAM in the diagnostic evaluation of morphologically suspected ESC-RCC.
Despite recent studies showing that dedifferentiated and undifferentiated melanoma (DM/UM) mimic sarcoma histologically, DM/UM continue to pose a diagnostic challenge owing to their under-recognition and frequent misclassification. To address this pitfall, we studied 22 cases of DM/UM initially classified as sarcoma. The patients were typically male (18/22) and older than 55 years (median 65 years, range 40-89 years), often lacking a history of melanoma (15/22). All but one case (21/22) presented with evidence of metastasis, and sites of disease frequently included lymph node basins, especially axilla (10/22). The tumors variably showed spindled and rhabdoid cytomorphology, collagenous or myxoid stroma, and fascicular architecture, imitating sarcoma; all tumors exhibited an intratumoral inflammatory component ranging from moderate to brisk. Molecular testing demonstrated alterations involving BRAF (7/22), NRAS/HRAS (10/22), NF1 (4/14), and TERT promoter (9/13). High tumor mutational burden was present in 13/13 cases (mean 21.8 mutations/Mb) and a UV-related mutational signature was found in 8/8. By immunohistochemistry, 55% (12/22) were negative for melanocytic markers, in keeping with undifferentiated melanoma. Two cases (2/17) were positive for desmin, while SATB2 was positive in 2/2 cases, including one with osteoid. The cohort showed strong expression of PD-L1 in all 22 cases (CPS 80-100, mean 93). In contrast, a separate cohort of 87 sarcomas of varying histotype had an average CPS of 5.6 (median CPS 0), including only three cases with CPS >50. Ten patients received PD-L1-targeted immunotherapy with partial or complete response in 80%. These findings emphasize pitfalls in distinguishing DM/UM from sarcoma and highlight the utility of PD-L1 immunohistochemistry in accurately diagnosing and effectively treating DM/UM.
The presence of oxyntic (body-type) glands in the duodenum is conventionally termed "gastric heterotopia" and is presumed to represent a congenital developmental anomaly. In contrast, gastric foveolar metaplasia of the duodenum is widely accepted as an acquired, reactive process. If duodenal gastric heterotopia were truly congenital, its prevalence should remain stable across age groups; if it is metaplastic in nature, prevalence should increase with age. A retrospective natural language search was performed for all cases diagnosed as "gastric heterotopia" in duodenal biopsies at a single academic medical center over a 10-year period (6/2013-4/2023). The prevalence of gastric heterotopia was calculated for each decade of life. Of 44,637 patients with duodenal biopsies, 846 (1.90%) had gastric heterotopia. The prevalence rose from 0.22% in patients aged 0-10 years to 4.05% in patients aged 91-100 years, representing an approximately 20-fold increase. The Spearman correlation between age group and prevalence was 0.988. The strong, monotonic relationship between patient age and prevalence of duodenal oxyntic glands is less consistent with a congenital process and instead supports a metaplastic etiology. The term "oxyntic metaplasia" is proposed as a more pathophysiologically accurate descriptor for this finding.
BACKGROUND:Solitary fibrous tumor (SFT) is a mesenchymal neoplasm characterized by NAB2::STAT6 fusion and nuclear STAT6 expression. Primary SFT of the prostate is rare, and its biological behavior remains incompletely defined. We present a multi-institutional cohort and comprehensive literature review to better characterize clinicopathologic features, management, and outcomes. DESIGN:We analyzed 33 patients with prostatic SFTs from multiple institutions, integrating clinical, radiologic, histopathologic, immunohistochemical, and follow-up data. A systematic review of published cases was performed, and findings were contextualized using established risk models. RESULTS:Patients ranged from 30 to 93 years (mean, 59; median, 61). Tumor sizes ranged from 0.6 to 19.5 cm (mean, 6.8; median, 5.75). Presenting symptoms included urinary obstruction, pelvic fullness, elevated PSA, or incidental detection. In two patients, the tumor caused urinary obstruction requiring transurethral resection. Location adjacent to the seminal vesicles was noted in several patients with one growing as a large mass into the pelvis. In several patients, the SFT was an incidental finding on needle biopsy performed for elevated PSA. Histologically, all tumors demonstrated classic SFT morphology with a spindle cell proliferation and patternless architecture. Tumor borders varied, with both well-circumscribed and infiltrative patterns observed. Cellularity ranged from low to high, and nuclear atypia was most often mild to moderate. Mitotic activity was generally low (<5 mitoses/10 HPF in most cases), although two tumors showed elevated indices (12 and 15/10 HPF). Necrosis was identified in 5 tumors and was focal in 3. STAT6 was positive in 27/27 tested cases (100%), and CD34 was positive in all cases with available results (31/31, 100%). Management was primarily surgical. Only three tumors in this cohort developed metastatic disease, limiting the ability to confirm or refute the applicability of the Demicco risk stratification model. Metastatic cases occurred in relatively older patients, two of the three were >5 cm with focal necrosis, and two had increased mitotic activity (>4/10 HPF), while the third was 4.5 cm without necrosis but showed a high mitotic count. No overtly high-grade morphology or consistent morphologic predictors of metastasis were identified in this series. Follow-up was available in 16 patients (10-171 months; mean, 38; median, 29). Aside from the three patients who developed metastatic disease, all others were alive and without recurrence or metastasis at last contact. CONCLUSIONS:This is among the largest reported cohorts of prostatic SFTs. These tumors, though rare in the prostate, appear to display similar morphologic and immunophenotypic features to SFTs in other anatomic sites. While generally indolent, rare cases may metastasize. Accurate diagnosis relies on a combination of morphologic evaluation and STAT6 IHC. This study expands the clinicopathologic spectrum of SFTs and emphasizes the need for long-term follow-up due to the potential for late recurrence or metastasis.
Acute myeloid leukemia (AML) is increasingly defined by recurrent genetic alterations that determine disease classification, prognosis, and therapeutic strategy. Although definitive diagnosis of genetically defined subtypes relies on cytogenetic and molecular techniques, careful evaluation of bone marrow and peripheral blood morphologic findings remains an essential and immediate component of the diagnostic process. Many genetic lesions in AML are associated with reproducible morphologic findings that can guide early diagnostic suspicion, inform triage of ancillary testing, and anticipate biologic behavior. This review summarizes the major genetically defined subtypes of AML and delineates their characteristic morphologic correlates, emphasizing how integration of microscopic findings with cytogenetic and molecular data enhances diagnostic precision. By revisiting morphology through a genomic lens, we underscore its continued central role in contemporary hematopathology.
