Context.—
The current College of American Pathologists reporting guideline for mismatch repair protein (MMRP) immunohistochemistry for Lynch syndrome (LS) screening considers the presence of any positive nuclear staining as intact MMRP expression. This would include tumors with combined areas of subclonal retention and loss of MMRP staining.
Objective.—
To evaluate the clinical significance of reporting subclonal staining patterns of MMRP immunohistochemistry in endometrial carcinoma.
Design.—
We retrospectively reviewed 455 consecutive MMRP immunohistochemistry results of endometrial carcinoma in hysterectomy specimens from 2012 through 2017 and identified cases with subclonal MMRP staining. These results were correlated with the patient's personal and family history of LS-associated carcinoma, MLH1 promoter methylation status, and LS genetic testing.
Results.—
Subclonal staining of MMRP was seen in 48 of 455 cases (10.5%) on review. Thirty cases demonstrated isolated subclonal staining and were reported by pathologists as follows: subclonal (n = 5), complete MMRP loss (n = 4), and intact MMRP (n = 21). Eighteen cases had subclonal staining in combination with complete loss of other MMRP. Cases reported as subclonal or complete MMRP loss had appropriate clinical follow-up. Two of 2 cases with isolated subclonal MSH6 loss tested positive for LS. One of 3 cases with isolated subclonal MLH1/PMS2 loss was negative for MLH1 promoter methylation; LS genetic testing was not performed because of cost.
Conclusions.—
Our study reveals that LS germline mutation can be detected in endometrial carcinoma patients whose tumors display sole subclonal MMRP staining. Our results stress the importance of reporting subclonal staining patterns to ensure appropriate clinical follow-up.
A variety of primary malignant mesenchymal neoplasms can arise from the perinephric soft tissue and hilar vessels and potentially involve the kidney, mimicking primary renal tumors. A search was made at our institution for patients that underwent radical nephrectomy with associated perinephric or hilar sarcomas from 2010 to 2021. Twenty-six patients were identified. Mean patient age was 60 years (range: 34–83 years), with 16 (62%) females and 10 (38%) males. The mean tumor size was 21.6 cm (range: 8.1–36.5 cm). Among the perinephric/retroperitoneal sarcomas, 14/20 (70%) were dedifferentiated liposarcoma, 4/20 (20%) were well-differentiated liposarcoma, and 2/20 (10%) were leiomyosarcoma. There were 4 grade 1 (20%; all well-differentiated liposarcoma), 9 grade 2 (45%), and 7 grade 3 (35%) tumors. All 6 sarcomas arising from the renal vein/inferior vena cava were leiomyosarcoma: grade 2 in 1 (17%), grade 3 in 4 (67%), and ungraded (due to neoadjuvant therapy effect) in 1 (17%) patient. Four of the 26 (15%) tumors involved the ipsilateral kidney. All 4 tumors were grade 3 sarcomas. On follow-up, 8/26 (31%) patients developed local recurrence and/or metastasis. The mean time for recurrence was 22 months (range: 7–48 months). Two patients progressed with metastasis to the lungs, both of which were grade 3 leiomyosarcoma, and appeared 11 months after the initial diagnosis. Our data suggest that while local recurrence is prevalent with most subtypes of perinephric sarcomas, high-grade leiomyosarcoma has a distinct proclivity for distant metastasis, with the lungs being the most common site.
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