Significance of anatomical gateways for tumor deposits in colon cancer
Tumor deposits are a crucial biomarker for colorectal cancer. They are closely associated with nearby structures, such as blood vessels, lymphatic vessels, and peripheral nerves, which serve as pathways that facilitate the spread of tumor cells throughout the body. The authors investigated how tumor deposits access these anatomical gateways and how invasion pattern impacts patient survival. For the study, they analyzed patients with colon carcinoma and tumor deposits who underwent surgery at Radboud University Medical Centre, Nijmegen, the Netherlands, between 1986 and 2012. Using serial sections and IHC with the antibodies CD34, D2-40, S100, and elastic van Gieson, they examined tumor deposit distribution and access to surrounding anatomical structures, including blood vessels, lymphatic vessels, and peripheral nerves. A total of 280 tumor deposits from 127 patients were examined. Of these, 112 (40 percent) deposits had multiple access points, 109 (39 percent) had a single access point, and 59 (21 percent) had no discernible access point. More than half (57 percent) of the tumor deposits demonstrated hematovascular invasion. Patients with tumor deposits featuring a single access point had a better prognosis compared with those who had multiple access points (five-year overall survival, p = .025; five-year disease-free survival, p = .005). Tumor deposits are a heterogeneous biomarker characterized by various access points, with hematovascular invasion being the most common. The authors concluded that this study highlights a direct correlation between the number of tumor deposit access points and patient outcomes, indicating that an increase in access points is linked to a poorer prognosis.
Oguz Erdogan AS, Brouwer NPM, Angerilli V, et al. The number of potential gateways determines prognostic value of tumour deposits in colon cancer. Pathology. 2025;57(5):564–569.
Correspondence: Dr. Ayse Selcen Oguz Erdogan at [email protected]
Primary cutaneous neoplasm with rhabdomyosarcomatous differentiation and a melanoma-like mutational landscape
Malignant melanoma is known for its wide range of morphologic variability. In rare cases, it may lose all melanocytic markers and adopt the morphologic and immunophenotypic characteristics of transdifferentiated malignant melanoma (TMM) in a process known as transdifferentiation. Distinguishing TMM from primary cutaneous neoplasms can be challenging and is often dependent on the identification of an adjacent conventional melanoma. Molecular analysis may be helpful in particularly difficult cases. The mutational landscapes of TMMs are highly similar to those of conventional melanomas—for example, mutations in NF1 and NRAS and variable BRAF V600E. The authors presented an exceedingly rare case of likely TMM with rhabdomyosarcomatous differentiation in which high tumor mutational burden (TMB) was an important clue to the diagnosis. An 83-year-old woman presented with an 8.2-cm fungating mass on the upper arm. Biopsy revealed a sheet-like proliferation of mitotically active pleomorphic cells that were positive for myogenin and MyoD1 and negative for S100 and SOX10. A diagnosis of epithelioid rhabdomyosarcoma was rendered. Subsequent axillary lymph node metastasis prompted whole exome sequencing, which revealed a molecular signature more indicative of malignant melanoma, including high TMB (19 mutations per megabase); ultraviolet mutational signature—that is, a preponderance of C>T base change; TERT promoter mutation; and ARID2 mutation. After discussion at an interdisciplinary tumor board, TMM was considered the most likely diagnosis, and the patient was started on pembrolizumab. Morphologic features more typical of malignant melanoma than cutaneous sarcomas, such as tumor-infiltrating lymphocytes, junctional epidermal tumor nests, and satellitosis, may be helpful in diagnosing TMM, which has important prognostic and therapeutic implications.
Weigelt MA, Pattali S, Dermawan JK, et al. Primary cutaneous neoplasm with rhabdomyosarcomatous differentiation and a melanoma-like mutational landscape. J Cutan Pathol. 2025;52(6):414–417.
Correspondence: Dr. Steven D. Billings at [email protected]
LGR5 as a diagnostic marker for dysplasia in serrated polyps
Wnt signaling pathway dysregulation is often a critical early component in colorectal neoplasia. Using the Wnt reporters LGR5 and AXIN2, the authors assessed whether these polyps demonstrate predictable expression patterns and if these patterns have diagnostic value. They evaluated 23 tubular adenomas (TA), 23 sessile serrated lesions (SSL), 14 SSL with dysplasia, and 38 traditional serrated adenomas (TSA). Chromogenic in situ hybridization stains (ISH) for LGR5 and AXIN2 were performed. Reactivity was defined as strong, intermediate, or weak. Upper third crypt reactivity was defined as full-thickness staining. Accentuation within ectopic crypts was recorded. The authors found that TA (91 percent) showed strong reactivity and full-thickness staining with LGR5. TSA showed full-thickness and weak to intermediate LGR5 reactivity (79 percent), and ectopic crypts with LGR5 accentuation were found exclusively in TSA. SSL showed weak LGR5 reactivity confined to the basal crypt region (100 percent). SSL with dysplasia also showed weak or intermediate LGR5 reactivity (100 percent), but the reactivity pattern was full thickness (88 percent). AXIN2 expression paralleled LGR5 expression (Pearson coefficient, 0.63) for signal intensity in the polyp groups examined. The authors concluded that qualitative and quantitative differences in AXIN2 and LGR5 expression assist in diagnosing SSL with dysplasia. In cases of SSL with equivocal dysplasia, full-thickness reactivity for LGR5 would be indicative of SSL with dysplasia. These distinctions are clinically relevant since SSL with conventional dysplasia are believed to represent more advanced lesions than sporadic adenomas and require enhanced surveillance.
Yilmaz O, Arora K, Lee SH, et al. LGR5 as a diagnostic marker for dysplasia in serrated polyps. J Clin Pathol. 2025. doi.org/10.1136/jcp-2024-209856
Correspondence: Dr. Vikram Deshpande at [email protected]