CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.
Flat pattern of nephrogenic adenoma unveiled using PAX2 and PAX8 immunohistochemistry
Nephrogenic adenoma is a benign lesion of the urinary tract, particularly the urinary bladder. It is a gross and microscopic mimicker of urothelial neoplasm or metastatic carcinoma. Several histological patterns—tubular, tubulocystic, polypoid, papillary, and fibromyxoid—have been recognized, but a flat pattern has not been described. Histologically, nephrogenic adenoma consists of tubules, cysts, or papillae lined by flat to polygonal cells with frequent hobnail appearance. The stroma is often edematous or has a granulation tissue-like appearance with acute or chronic inflammation. By immunohistochemistry, nephrogenic adenomas are positive for the renal epithelial markers CK7, CD10, and alpha-methylacyl-coenzyme A racemase and negative for bladder urothelium or prostate markers. Recent studies have shown that nephrogenic adenomas are positive for PAX2 and PAX8. The authors encountered an interesting case of tubular nephrogenic adenoma with adjacent areas suspicious of flat urothelial atypia. Immunohistochemistry for PAX2 and PAX8 were positive in these areas, unveiling a flat pattern of nephrogenic adenoma. This case prompted the authors to study 15 cases of nephrogenic adenoma to determine additional instances of flat pattern and to assess the value of PAX2 and PAX8 immunoreactivity in diagnosing nephrogenic adenoma. PAX2 and PAX8 immuno-staining was positive in 14 of 15 and 15 of 15 cases, respectively. The flat pattern was present at least focally adjacent to tubular, polypoid, and papillary areas in eight of 15 cases of nephrogenic adenoma. The authors concluded that the flat pattern is a common finding in nephrogenic adenomas but easily underrecognized by morphologic examination, and it may be confused with flat urothelial lesions with atypia. Immunostains for PAX2 and PAX8 are useful in detecting nephrogenic adenomas and unveil those nephrogenic adenomas with a flat pattern.
Piña-Oviedo S, Shen SS, Truong LD, et al. Flat pattern of nephrogenic adenoma: previously unrecognized pattern unveiled using PAX2 and PAX8 immunohistochemistry. Mod Pathol. 2013;26:792–798.
Correspondence: Dr. J. Y. Ro at jaero@tmhs.org
Managing borderline atypical ductal hyperplasia/ductal carcinoma in situ on breast needle core biopsy
The differential diagnosis of low-nuclear grade intraductal epithelial proliferations of the breast includes atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). This distinction can be difficult on core needle biopsy but can have significant clinical ramifications. The authors examined the clinical course of patients diagnosed with borderline ADH/DCIS lesions (marked ADH [MADH]) via core needle biopsy at their institution. Seventy-four patients were diagnosed with MADH on core needle biopsy and underwent an excisional biopsy. The majority of the core needle biopsies reviewed at outside hospitals had been classified as DCIS. Twenty patients (27 percent) had benign findings or lobular neoplasia in their excisional biopsy, 18 (24 percent) had ADH, 33 (45 percent) had DCIS, and three (four percent) had DCIS and invasive ductal carcinoma. None of the 38 patients who were not diagnosed with DCIS or invasive ductal carcinoma on excisional biopsy underwent further surgery or radiation postoperatively. Thirty-seven of these 38 patients had no recurrences, and one patient developed a recurrence that on our review was likely residual localized MADH. The mean followup for these patients was 54 months. Of the 36 patients diagnosed with DCIS or invasive ductal carcinoma on excisional biopsy, fewer than 20 percent required mastectomy. On review, MADH involving an intermediate-sized duct on core needle biopsy and the amount of residual lesion on imaging were significantly associated with DCIS or invasive ductal carcinoma on excisional biopsy. Conversely, MADH involving columnar cell lesions and calcification on core needle biopsy were significantly associated with benign pathology on excisional biopsy. The authors concluded that their study provides preliminary data that justify a conservative approach to managing borderline ADH/DCIS lesions on core needle biopsy—that is, diagnose as MADH and treat by conservative excision.
Vandenbussche CJ, Khouri N, Sbaity E, et al. Borderline atypical ductal hyperplasia/low-grade ductal carcinoma in situ on breast needle core biopsy should be managed conservatively. Am J Surg Pathol. 2013;37(6):913–923.
Correspondence: Dr. Pedram Argani at pargani@jhmi.edu
Classic lobular neoplasia on core biopsy: a clinical and radiopathologic study with followup excision biopsy
No consensus guidelines exist for managing lobular neoplasia diagnosed on core biopsy as the highest risk factor for cancer. The authors conducted a study to assess the risk of upgrade (invasive carcinoma or ductal carcinoma in situ) at the site of the lobular neoplasia and any clinical, radiological, or pathologic factors associated with the upgrade. They reviewed all cases with a diagnosis of lobular neoplasia on core biopsy from June 2006 to June 2011. Any cases with radiopathologic discordance, coexistent lesion that required excision (atypical ductal hyperplasia, flat epithelial atypia, duct papilloma or radial scar), or nonclassic variant of lobular carcinoma in situ (pleomorphic, mixed ductal and lobular, lobular carcinoma in situ with necrosis) were excluded from the study. Core biopsy indications included calcification in 35 cases (40 percent), non-mass–like enhancement in 19 (22 percent), mass lesion in 31 (36 percent), and mass as well as calcification in two (two percent). Followup excisions were studied for upgrades. The study cohort included 87 cases and showed an upgrade of 3.4 percent (95 percent confidence interval, 1–10 percent). Three cases showed an upgrade—one ductal carcinoma in situ and two invasive cancers. All upgraded cases were a breast imaging-reporting and data system score of four or greater and associated with atypical ductal hyperplasia or in situ or invasive cancer in prior or concurrent biopsies in either breast. The number of cores and lobules involved, pagetoid duct involvement, presence of microcalcification in lobular neoplasia, needle gauge, and number of cores obtained showed no correlation with upgrade. The results suggest that with radiopathologic concordance and no prior biopsy-proven risk for breast cancer, a core biopsy finding of lobular neoplasia as the highest risk lesion can be managed appropriately and safely with clinical and radiologic followup as an alternative to surgical excision.
Chaudhary S, Lawrence L, McGinty G, et al. Classic lobular neoplasia on core biopsy: a clinical and radio-pathologic correlation study with follow-up excision biopsy. Mod Pathol. 2013;26:762–771.
Correspondence: Dr. T. Bhuiya at tbhuiya@nshs.edu
Intestinal-type endocervical adenocarcinoma in situ: a subset of AIS affecting older women
Conventional endocervical adenocarcinoma in situ (cAIS) is typically strongly and diffusely positive for p16 and has a high Ki67 index consistent with its frequent association with high-risk human papillomavirus (HPV) infection. The intestinal variant (iAIS) is less common, and its relationship to HPV infection has not been thoroughly examined. The authors compared the clinicopathologic features, frequency of HPV infection, and expression of CDX2 and surrogate biomarkers of HPV infection (p16, Ki67) in cAIS with those of iAIS. They identified 86 cases with a diagnosis of AIS (49 iAIS, 37 cAIS) from their multi-institutional files. Of these, 13 iAIS and 20 cAIS cases had slides and tissue available for histopathologic review, immunohistochemical analysis, and molecular tests. All 86 cases were used to evaluate clinical parameters. However, HPV DNA analysis and immunohistochemical analysis for p16, MIB-1, CDX2, and p53 were performed only on those cases for which slides or paraffin blocks were available. The average age at diagnosis was significantly higher in iAIS than in cAIS (44.5 versus 32.6 years; P=0.0001). All 20 cAIS cases showed moderate to strong and diffuse p16 staining, but only nine of 13 iAIS cases showed this degree of p16 staining, and four of 13 iAIS cases showed weak and patchy distribution (P<0.02). Only six of nine iAIS cases were positive for HPV type 18 (five cases) or 33 (one case), in contrast to 11 of 11 conventional cAIS cases (P=0.04). Similarly, 12 of 14 cAIS but only five of 13 iAIS cases showed a high Ki67 proliferative index. CDX2 was positive in all iAIS cases and p53 was negative. The authors concluded that most iAIS cases are positive for high-risk HPV and show moderate to strong and diffuse p16 staining. However, a subset of iAIS shows variable staining with p16 and Ki67, is not associated with HPV, and occurs in a distinctly older age group, suggesting an alternative pathogenesis. Recognizing that iAIS can show variable staining for p16 and Ki67 is important when resolving problematic endocervical lesions, particularly in small biopsies with unusual p16 staining patterns.
Howitt BE, Herfs M, Brister K, et al. Intestinal-type endocervical adenocarcinoma in situ: an immunophenotypically distinct subset of AIS affecting older women. Am J Surg Pathol. 2013;37:625–633.
Correspondence e-mail address not provided.