Intraoperative evaluation of the nipple/subareolar tissue during nipple sparing mastectomy: Accuracy, pathological correlation and clinical significance [Meeting Abstract]
Background: Intraoperative evaluation of the nipple/subareolar tissue (N/SAT) has been used by surgeons to assess for occult nipple involvement by malignancy and guide the decision-making process for nipple preservation during nipple sparing mastectomies (NSM). The aim of our study is to evaluate significance and accuracy of frozen section (FS) results compared to final pathology/permanent sections.
Design(s): We retrospectively reviewed records of patients that underwent NSM with FS of the N/SAT from 2014 to 2018. Positive FS or final pathology results include atypical hyperplasia, in situ and invasive carcinoma.
Result(s): Over a 5-year period a total of 339 NSM cases utilized FS to evaluate the N/SAT. Of the total 339 cases, 85(25%) were prophylactic and 254(75%) were therapeutic mastectomies. All 85 prophylactic mastectomies were negative (benign) on FS and final diagnosis. Among 254 therapeutic mastectomies, 217(85.4%) showed negative (benign) intraoperative FS with concordant benign final pathology; 22(8.7%) showed positive intraoperative FS with concordant positive final pathology; 15(5.9%) were false negative (benign) on FS and positive on final permanent sections (figure 1). Positive results consisted of atypical ductal or lobular hyperplasia (5, 27.8%), in situ ductal or lobular carcinoma (11, 61.1%) and invasive carcinoma (1, 5.6%). One false positive case showed "atypical intraductal proliferation" at FS and was diagnosed as intraductal papilloma on final pathology; the nipple was not removed at the time of surgery. Of the 37 cases with positive final nipple pathology, 14(37.8%) had intraoperative resection of the nipple/areola complex (NAC), 9(24.3%) required an additional surgery for removal of NAC and 13(35.1%) had no additional procedures performed. Residual pathology was identified in 9(39.1%) of the resected NAC. In our patient cohort frozen section diagnosis has a sensitivity of 58.3%, specificity of 99.5%, positive predictive value (PPV) of 95.5% and negative predictive value (NPV) of 93.5%. (Figure presented)
Conclusion(s): Intraoperative evaluation of the N/SAT is highly accurate (93.7%) and specific (99.5%) test that prevented additional surgical intervention in 8.7% of therapeutic mastectomies. At the same time, surgeons should be aware of the low/moderate sensitivity of intraoperative FS, which may be explained by processing artifacts, sampling or cautious approach not to overcall the FS findings
Microglandular Adenosis is an advanced precursor breast lesion with evidence of molecular progression to matrix-producing metaplastic carcinoma
Microglandular adenosis (MGA) is a rare breast lesion reported to be associated with invasive carcinoma in up to 20-30% of cases, and has been proposed as a non-obligate precursor to basal-like breast cancers. We identified a case of matrix-producing metaplastic carcinoma with morphologic and immunohistochemical evidence of progression from MGA to atypical MGA (AMGA), carcinoma in situ (CIS) and invasive carcinoma. We performed whole exome sequencing of each component (MGA, AMGA, CIS and cancer) to characterize the mutational landscape of these foci. There was significant copy number overlap between all foci, including a segmental amplification of the CCND1 locus (partial chromosome 11 trisomy) and MYC (8q24.12-13). Using a bioinformatics approach, we were able to identify three putative mutational clusters and recurrent, stop-gain non-synonymous mutations in both ZNF862 and TP53 that were shared across all foci. Finally, we identified a novel deleterious splice-acceptor site mutation of chr5:5186164G>T (chromosome 5p15) encoding the gene, ADAMTS16, in the invasive component.
A Note of Caution: Variable Cytokeratin Staining in Sentinel Node Metastases
Sentinel lymph node biopsy is the current standard procedure used to stage patients with breast cancer. The best histological method in evaluating sentinel nodes is highly debated among institutions and is thus not standardized. The optimal histological analysis is a balance between comprehensive evaluation of the sentinel nodes and cost effectiveness. One commonly used approach is serial sectioning and alternately staining with hemotoxylin and eosin and AE1/AE3 cytokeratin immunohistochemistry analysis. We report 2 cases of metastatic carcinoma demonstrating negative staining for AE1/AE3. This observation highlights a rare but potential pitfall to this commonly used strategy in assessing sentinel lymph node biopsies in breast cancer.
Pulmonary metastasis in a patient with simultaneous bladder cancer and relapsing granulomatosis with polyangiitis
Background Granulomatosis with polyangiitis (GPA) relapse can complicate the differential diagnosis of pulmonary lesions. Case Report A 70-year-old male smoker with GPA and emphysema presented with dyspnea, dry cough, and a right upper lobe pulmonary ground-glass opacity that persisted despite antibiotics. A trans-bronchial biopsy did not reveal active vasculitis, malignancy, or infection. He was treated for presumed GPA relapse based on pulmonary manifestations, renal failure, and elevated PR3-ANCA. Later, hematuria led to the cystoscopic discovery of a bladder wall lesion, which was diagnosed as micropapillary urothelial carcinoma not involving the muscularis propria. The patient developed an increasing pulmonary infiltrate with a new solid component, satellite lesions, and regional lymphadenopathy. A right upper lobe wedge resection showed metastatic urothelial carcinoma. Conclusions The simultaneous presentation of a pulmonary lesion and GPA relapse is a diagnostic challenge. The differential diagnosis should include the rare possibility of metastatic urothelial carcinoma, regardless of how the lesion appears radiographically.
Aspiration biopsy of nodular pseudoangiomatous stromal hyperplasia of the breast: Clinicopathologic correlates in 10 cases
Nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast is rare and often indistinguishable from fibroadenoma, clinically and on aspiration biopsy smears. We report our observations in 10 patients with PASH, evaluated by fine-needle aspiration (FNA) biopsy and core biopsy.We retrospectively reviewed the clinical, radiographic, cytologic, and histologic findings in 10 cases of pure nodular PASH.Ten patients with a presumed clinical and radiologic diagnosis of fibroadenoma underwent aspiration biopsy. The aspiration smears were diagnosed as fibroadenoma (4 cases), cellular fibroadenoma (1 case), schwannoma versus neurofibroma (1 case), fibrocystic change (3 cases; 2 with atypia), and 'not specific for a lesion' (1 case). A diagnosis of PASH was not suspected in any case. A discrepant or imprecise cytologic diagnosis and /or the presence of dissociated spindle or epithelial cells, or cellular stromal fragments prompted a surgical excision in 7 of 10 patients (70%). The remaining 3 patients exhibited cytologic features of fibroadenoma and were diagnosed as such; however, surgical excision was recommended. Three patients underwent a subsequent core biopsy, with a diagnosis of PASH being made in 1 patient.FNA biopsy could not discriminate PASH from fibroadenoma in 4 of 10 patients (40%) or suggest a diagnosis of PASH in any case. On retrospective review, the finding of plump, spindle-shaped mesenchymal cells may be a cytologic clue to suggest a diagnosis of PASH. Diagn. Cytopathol. 2005;32:345-350. (c) 2005 Wiley-Liss, Inc