Upgrade rates of variant lobular CIS compared with classic lobular CIS diagnosed on core needle biopsy
The authors conducted a study to determine the upgrade rates of variant lobular carcinoma in situ (V-LCIS)—that is, combined florid LCIS (F-LCIS) and pleomorphic LCIS (P-LCIS)—compared with classic LCIS (C-LCIS) when diagnosed on core needle biopsy (CNB). The secondary goal of the study was to determine the rate of progression or development of invasive carcinoma on long-term follow-up after primary excision. After institutional review board approval, the authors’ institutional pathology database was searched for patients with “pure” LCIS diagnosed on CNB who underwent subsequent excision. Radiologic findings were reviewed, radiologic-pathologic (rad-path) correlation performed, and follow-up patient outcome data obtained. A total of 120 cases of LCIS were identified on CNB (C-LCIS=97, F-LCIS=18, and P-LCIS=five). Overall upgrade rates after excision for C-LCIS, F-LCIS, and P-LCIS were 14 percent (14 of 97), 44 percent (eight of 18), and 40 percent (two of five), respectively. Seventy-nine (66 percent) of the total cases were deemed rad-path concordant. Of these, the upgrade rates after excision for C-LCIS, F-LCIS, and P-LCIS were 7.5 percent (five of 66), 40 percent (four of 10), and zero (zero of three), respectively. The overall upgrade rate for V-LCIS was higher than for C-LCIS (P=.004), even for the cases deemed rad-path concordant (P=.036). Twenty-three of 24 upgraded cases showed pT1a or lower disease. With an average follow-up of 83 months, invasive carcinoma in the ipsilateral breast was identified in seven percent (eight of 120) of cases. Six patients had died: two from contralateral breast cancer and four from other causes. Because of a high upgrade rate, V-LCIS diagnosed on CNB should be excised. The upgrade rate for C-LCIS (even when rad-path concordant) in this study is higher than that reported in many other studies. Rad-path concordance read, surgical consultation, and individualized decision-making are recommended for C-LCIS cases. The risk of developing invasive carcinoma after LCIS diagnosis is seven percent with an approximately seven-year follow-up, but active surveillance is required to diagnose early stage disease. The authors concluded that due to the low incidence and lack of outcome data for V-LCIS, a tailored approach with multidisciplinary consultations and risk assessment is warranted. More research is needed to better understand progression of the disease, resolve issues, and standardize diagnosis and treatment.
Harinath L, Villatoro TM, Clark BZ, et al. Upgrade rates of variant lobular carcinoma in situ compared to classic lobular carcinoma in situ diagnosed in core needle biopsies: a 10-year single institution retrospective study. Mod Pathol. 2024;37. doi:10.1016/j.modpat.2024.100462
Correspondence: Dr. Rohit Bhargava at bharrx@upmc.edu
Morphologic and phenotypic overlap of POU2F3-expressing SCLC and LCNEC
Given the differences in protein expression in small cell lung carcinoma (SCLC) by molecular type, it is likely that there are differences in morphology, but, to the authors’ knowledge, the relationship between molecular classification and morphology has not been examined. Studies are also lacking with regard to applying this molecular classification to large-cell neuroendocrine carcinoma (LCNEC). Therefore, the authors investigated the relationship between IHC-based molecular classification and morphology, protein expression, and the clinical features of 146 consecutive pulmonary neuroendocrine carcinoma (NEC) resection specimens, focusing primarily on POU2F3, the master transcription factor involved in tuft cell generation. POU2F3-dominant SCLC (n=24) and LCNEC (n=14) showed overlap in cytomorphology, while non-POU2F3–dominant SCLC (n=71) and LCNEC (n=37) showed distinct differences in cytomorphology. POU2F3-dominant NEC also exhibited significantly more abundant tumor stroma, more prominent nest formation, more frequent bronchial intraepithelial involvement, and less frequent background fibrosis than non-POU2F3–dominant NEC. Immunohistochemically, POU2F3-dominant SCLC and LCNEC were characterized by lower expression of TTF-1, CEA, and neuroendocrine markers and higher expression of bcl-2, c-Myc, and c-kit. Those with POU2F3-dominant NEC had a significantly better prognosis for recurrence-free survival than those with non-POU2F3–dominant NEC. POU2F3-dominant NEC was characterized by a higher smoking index than non-POU2F3–dominant NEC. It also formed a distinct group exhibiting intermediate morphology between SCLC and LCNEC, with distinct protein expression as tuft cell-like carcinoma. Recognizing this unique subtype may provide clues for solving the long-standing issues of neuroendocrine carcinoma and appropriate therapeutic stratification. The authors concluded that it is important to identify POU2F3-expressing carcinomas by IHC and analyze their clinicopathological features.
Jimbo N, Ohbayashi C, Takeda M, et al. POU2F3-expressing small cell lung carcinoma and large cell neuroendocrine carcinoma show morphologic and phenotypic overlap. Am J Surg Pathol. 2024;48:4–15.
Correspondence: Dr. Naoe Jimbo at naoe1123@med.kobe-u.ac.jp