This Week in Pathology — Jul 11, 2026

Welcome to This Week in Pathology. This week we're covering 10 notable papers spanning diagnostic updates in genitourinary and renal neoplasms, emerging classification frameworks in thoracic and breast pathology, and advanced diagnostic strategies in hematopathology and soft tissue tumors. Let's dive in.

We begin with significant updates in genitourinary and renal pathology, where evolving classifications and molecular insights are redefining classic diagnostic categories. In the journal Histopathology, the Testicular Sex Cord-Stromal Tumour group, collaborating with the Genitourinary Pathology Society and the International Society of Urological Pathology, has proposed a revised, hierarchical classification system for testicular sex cord-stromal tumours, termed the TESST classification [1]. Historically, these rare neoplasms were classified almost entirely on morphology, often relying on their resemblance to ovarian counterparts. However, recent evidence has highlighted distinct clinicopathological and molecular differences. The new four-tiered framework organizes these tumors by group, category, entity, and histological pattern, providing a structured approach to improve clinical management and guide future research. In renal pathology, recognizing specific morphologic patterns can be the key to identifying underlying syndromic conditions. Writing in The American Journal of Surgical Pathology, researchers investigated histiocyte-rich renal epithelial neoplasms, which are characterized by acinar spaces lined by oncocytic epithelial cells distended by luminal histiocytes [4]. In their study of 11 previously unreported cases, nearly half of the patients demonstrated mutations in the folliculin gene, with at least three cases showing evidence of occult Birt-Hogg-Dubé syndrome. Interestingly, all folliculin-mutated tumors were diffusely positive for glycoprotein nonmetastatic B, and the syndromic cases showed similar precursor-like cysts in the adjacent kidney. This morphologic pattern serves as an important diagnostic clue, prompting clinicians to evaluate for Birt-Hogg-Dubé syndrome. Meanwhile, another study in Histopathology raises a provocative question regarding the very existence of renal haemangioblastoma [10]. The authors present evidence suggesting that these tumors should instead be classified within the spectrum of MTOR-associated renal cell carcinoma with fibromyomatous stroma. This finding highlights the clinical importance of genetic and pathway-level analysis over morphology alone in renal neoplasia, as it may completely shift how these lesions are managed.

Moving on to thoracic and breast pathology, we address several diagnostic pitfalls and borderline lesions. In Modern Pathology, a study examines a common yet under-recognized phenomenon in pulmonary carcinoids that can easily lead to a misdiagnosis of paraganglioma [3]. Traditionally, the presence of sustentacular cells and the absence of keratin expression have been used to rule out carcinoids in favor of paraganglioma. However, the authors found that 17 percent of 109 lung carcinoids exhibited low labeling for the cytokeratin cocktail AE1/AE3, with three cases being entirely negative. Furthermore, over a third of the carcinoids contained diffuse sustentacular cells, and 14 percent were both AE1/AE3-low and sustentacular cell-positive. This overlapping profile can be resolved by using alternative keratins, such as OSCAR or cytokeratin 18, and tumor-specific transcription factors like OTP, GATA3, and PHOX2B, which remain highly reliable. In The Journal of Pathology, researchers explored the clinical and molecular landscape of bronchiolar adenoma-like lesions with atypical features, such as basal cell hyperplasia, partial loss of the basal layer, and cytological atypia [8]. By analyzing 19 cases, they demonstrated that these atypical lesions represent a morphological continuum ranging from benign bronchiolar adenoma to malignant lesions. Genetic profiling revealed a variety of driver events, including BRAF, EGFR, and MET mutations, with pathogenic TP53 mutations restricted to lesions with marked atypia. While all patients in this cohort remained disease-free after complete surgical resection, the presence of these molecular alterations suggests that these lesions require careful integration of histomorphology and molecular testing. In breast pathology, flat epithelial atypia remains a challenging borderline lesion situated between benign columnar cell change and flat low-to-intermediate-grade ductal carcinoma in situ. A review in Histopathology proposes a pragmatic, context-integrated diagnostic framework for flat epithelial atypia [5]. While these lesions share molecular alterations like chromosome 16q loss and 1q gain with low-grade ductal carcinoma in situ, these markers are not specific. The author emphasizes that the clinical significance of flat epithelial atypia is highly context-dependent, and pure, adequately sampled lesions have low upgrade rates, supporting a shift toward selective conservative management rather than routine aggressive excision.

In the field of hematopathology, modern diagnostics are increasingly reliant on highly sensitive testing and specific immunophenotypic surrogates. A comprehensive review in the American Journal of Clinical Pathology outlines the essential role of measurable residual disease, or MRD, in the clinical management of acute leukemia, multiple myeloma, and chronic lymphocytic leukemia [7]. Pathologists are vital in implementing and interpreting these advanced flow cytometry and molecular assays, which hold immense prognostic value and directly guide therapy in the absence of morphologic disease. Also in the American Journal of Clinical Pathology, a study characterizes the rare subset of plasma cell neoplasms harboring the immunoglobulin heavy chain and cyclin D3 translocation, which represents less than one percent of cases [9]. In their series of 16 patients, the authors observed that these neoplasms frequently exhibit lymphoplasmacytoid morphology and express CD20, CD56, and CD117, closely mimicking the more common translocation 11;14 positive neoplasms. Crucially, the researchers demonstrated that cyclin D3 immunohistochemistry, especially when performed as a dual stain with CD138, is a highly sensitive and specific surrogate for detecting this translocation. This simple immunohistochemical tool can help pathologists rescue these cases from being misclassified as partner-negative, triggering appropriate cytogenetic confirmation.

Finally, we turn to soft tissue and gastrointestinal oncology, where new molecular and diagnostic frameworks are emerging. In Histopathology, researchers characterized 39 cases of MAP3K-rearranged myxoid tumors, which represent a molecularly distinct subset of benign soft tissue neoplasms [6]. These tumors, typically found in superficial locations in middle-aged adults, histologically mimic cellular myxoma but lack the classic GNAS mutations. Instead, they harbor diverse MAP3K gene fusions, most commonly MSI2::MAP3K3 and MAP3K8::MAP3K3. Transcriptomic analysis showed that these tumors cluster closely with GNAS-mutant myxomas and show proximity to myxofibrosarcomas, but clinically they follow an indolent course, highlighting the importance of distinguishing them from low-grade sarcomas to avoid over-treatment. Lastly, a critical appraisal in The Journal of Pathology addresses the persistent knowledge gaps in the newly released sixth edition of the World Health Organization Classification of Tumours of the Digestive System [2]. While the new edition provides updated guidance on gastrointestinal cancers, the authors identify urgent research needs in precursor lesions and rare cancers, such as gastric dysplasia, serrated polyposis, and rare subtypes of colorectal and anal cancers. Pathologists are urged to participate in collective registries and collaborative research to help resolve these gaps for future editions.

If you only have time for one paper this week, make it the study on lung carcinoids with sustentacular cells and low keratin expression from Modern Pathology [3]. This paper provides highly practical, practice-changing guidance for a common diagnostic pitfall, demonstrating how an expanded immunohistochemical panel can prevent the misdiagnosis of a lung carcinoid as a paraganglioma.

Here are the key takeaways from this week in Pathology:

First, when evaluating suspected pulmonary paragangliomas, be aware that up to 17 percent of lung carcinoids can exhibit low or negative AE1/AE3 expression and contain sustentacular cells; expand your panel to include alternative keratins like OSCAR or cytokeratin 18, alongside transcription factors like OTP.

Second, a histiocyte-rich morphologic pattern in renal epithelial neoplasms is strongly associated with folliculin mutations and should prompt clinical evaluation for occult Birt-Hogg-Dubé syndrome.

Third, cyclin D3 immunohistochemistry is a highly sensitive surrogate marker that can identify rare plasma cell neoplasms harboring the IGH::CCND3 translocation, particularly those with lymphoplasmacytoid features that test negative for cyclin D1.

Fourth, flat epithelial atypia of the breast should be managed conservatively when presenting as a pure, adequately sampled lesion, as its clinical significance is highly context-dependent with low upgrade rates.

And fifth, MAP3K-rearranged myxoid tumors represent a distinct, benign soft tissue entity that must be distinguished from low-grade myxofibrosarcoma to prevent unnecessary aggressive treatment.

That's your roundup for This Week in Pathology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.