Case 1F -

Columnar cell alteration with atypia

History: This stereotactic core needle biopsy specimen is from a 42 year old with mammographically-detected microcalcifications. What is your recommendation? Case 1F - Figure 1 Case 1F - Figure 2 Diagnosis: Columnar cell alteration with atypia. Recommendation: Open biopsy. Discussion: Columnar cell alteration involving lobular units has been around for years. This entity has been termed as columnar cell hyperplasia, columnar metaplasia, expanded lobular units with columnar alteration, blunt duct adenosis, atypical lobules type A of minimal severity, hypersecretory hyperplasia, and most recently, columnar alteration with prominent apical snouts and secretions (CAPSS). Fraser et al. defined the pathologic spectrum and mammographic features of these lesions and were the first to coin the term "CAPSS." Currently, this lesion appears to be recognized more frequently in core needle biopsy material. The entity represents a spectrum of lesions with the lower end showing columnar alteration of the lobular unit and the upper end showing ductal carcinoma in situ. These lesions often present mammographically as a cluster of indeterminate microcalcifications requiring biopsy. Histologically, the terminal duct lobular units are expanded and lined by columnar epithelial cells with increased amount of cytoplasm, apical snouts (hobnail cells), luminal secretions and often calcifications. Some of these lesions present with cytologic and architectural atypia creating diagnostic difficulties, especially on core needle biopsy specimens. Fraser et al. termed CAPSS with atypia when the lining cells had an increased nuclear to cytoplasmic ratio with enlarged nuclei, vesicular chromatin and prominent nucleoli. Some cases of CAPSS with atypia might be considered by some to represent examples of the lesion known as the "clinging" variety of intraductal carcinoma or intraductal carcinoma involving lobular units described by Goldstein and O'Malley. Fraser et al. used the term atypical ductal hyperplasia or intraductal carcinoma when there were architectural abnormalities (epithelial stratification, tufting, and the formation of bridges or arcades) in addition to cytologic atypia. They concluded from their study: (1) CAPSS was a frequent finding in breast biopsy specimens performed for mammographically-detected microcalcifications, (2) CAPSS without atypia does not appear to be associated with an increased incidence of intraductal carcinoma or invasive carcinoma, and (3) CAPSS with atypia is more frequently associated with diagnostic areas of intraductal carcinoma. Recently, three groups looked at whether an open biopsy should be performed when columnar cell alteration is identified on core needle biopsy. The study by Brogi and Tan from Memorial Sloan-Kettering Cancer Center identified 23 patients where columnar alteration was diagnosed on core needle biopsy and an open biopsy was performed. The core needle biopsy was initially diagnosed benign in 6 cases and atypical in 17 cases. They reclassified these 23 cases based on the architectural features of the lesion as mild in 5 cases (1 cell layer), moderate in 6 cases (2-4 cell layers), and severe in 12 cases (5 cell layers, ± micropapillary tufts, ± cribriform spaces). There was significant pathology (DCIS or invasive carcinoma) in seven (30%) excisional biopsy cases. These 7 cases corresponded to 3 cases designated as moderate and 4 cases designated as severe. Based on their findings, they recommend that excisional biopsy be performed following the identification of columnar cell change of moderate or severe extent on core needle biopsy of mammographically detected calcifications. The second study by Harigopal et al. identified 46 consecutive cases diagnosed as columnar cell alteration on core needle biopsy. Twenty-six patients went to open biopsy (10 without atypia, 6 with cytologic atypia, 10 with architectural atypia). None of the 10 cases without atypia showed atypia or malignancy. The remaining 16 cases performed for diagnosis of columnar alteration with atypia showed atypical ductal hyperplasia and/or lobular carcinoma in situ in 5 (31%) cases and ductal carcinoma in situ and tubular carcinoma in one (6%) case. They concluded that management of columnar cell alteration without atypia remains controversial, but indicated that their data would support that open biopsy may not be necessary when a diagnosis of columnar cell alteration without atypia is made by core needle biopsy. In a more recent study, Guerra-Wallace et al. looked at CAPSS with and without atypia diagnosed on core needle biopsy. Thirty-seven cases with CAPSS on initial core biopsy went to subsequent open biopsy. Only 1 case at excision demonstrated DCIS when no atypia was identified on the core needle biopsy. In contrast, 3 (10%) cases were diagnosed as DCIS and 1 (3%) case was diagnosed as invasive carcinoma at open biopsy when CAPSS with atypical features was present on the core needle biopsy. They concluded that CAPSS with atypical features was significantly more likely to be associated with a cancerous lesion than those without atypical features, suggesting that a patient with a core needle biopsy showing CAPSS with atypia should undergo surgical excision.. In a recent abstract by Nasser et al., 27 cases of atypical columnar cell hyperplasia was identified on core needle biopsy. They grouped these lesions into 3 groups based on the number of cell layers (Group 1 – 1-2 cell layers, Group 2 – 3-6 cell layers, Group 3 - > 6 cell layers), which is different criteria used previously by Brogi et al. The number of foci of columnar cell hyperplasia was also recorded. They concluded that atypical columnar cell hyperplasia diagnosed on core needle biopsy was associated with DCIS and/or invasive carcinoma in nearly a quarter of cases, especially for those lesions categorized in Groups 2 and 3 and in those core needle biopsies that had 4 or more foci of atypical columnar cell hyperplasia. Based on their findings, surgical excision is warranted when atypical columnar cell hyperplasia is diagnosed on core needle biopsy. It is becoming clear how to handle these lesions when identified on core needle biopsy. What remains consistent is when atypia is found on core needle biopsy, open biopsy should be performed. References: Brogi E, Tan LK. Findings at excisional biopsy performed after identification of columnar cell change of ductal epithelium in breast core biopsy. Modern Pathology 2002; 15:29A. Fraser JL, Raza S, Chorny K, Connolly JL, Schnitt SJ. Columnar alteration with prominent apical snouts and secretions. A spectrum of changes frequently present in breast biopsies performed for microcalcifications. AJSP 1998; 22:1521-1527. Goldstein NS , O'Malley BA. Cancerization of small ectatic ducts of the breast by ductal carcinoma in situ cells with apocrine snouts. AJCP 1997; 107:561-566. Guerra-Wallace MM, Christensen WN, White RL. A retrospective study of columnar alteration with prominent apical snouts and secretions and the association with cancer. The American Journal of Surgery 2004, 188:295-398. Harigopal M, Yao DX, Hoda SA, DeLellis RA, Vazquez MF. Columnar cell alteration diagnosed on mammotome core biopsy for indeterminate microcalcification: Results of subsequent mammograms and surgical excision. Modern Pathology 2002; 15:36A. Nasser SM, Fan MJ. Does atypical columnar cell hyperplasia on breast core biopsy warrant follow-up excision? Mod Pathol 2003; 116:42A. Page DL, Kasami M, Jensen R. Hypersecretory hyperplasia with atypia in breast biopsies. What is the proper level of clinical concern? Pathology Case Reviews 1996; 1:36 -40.