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  Anatomic Abstracts

 

 

 

 

February 2011

Editors:
Michael Cibull, MD
Melissa Kesler, MD
Rouzan Karabakhtsian, MD
Megan Zhang, MD

Intensity-modulated radiotherapy outcomes for OPSCC patients stratified by p16 status Intensity-modulated radiotherapy outcomes for OPSCC patients stratified by p16 status

The authors conducted a study in which patients with oropharyngeal squamous cell carcinoma treated with intensity-modulated radiotherapy were stratified by p16 status, neck dissection, and chemotherapy to correlate these factors with outcomes. They retrospectively analyzed 112 patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with intensity-modulated radiotherapy (IMRT) from 2002 to 2008. All patients received RT to 66–70 Gray. Forty-five of the tumors were p16 positive (p16+), 27 were p16 negative (p16–), and 41 had unknown p16 status. Sixty-two patients had postradiation neck dissections. Nine patients with p16– tumors and 28 patients with p16+ tumors received chemotherapy. The distribution of T, N, and stage grouping among the p16+ and p16– patients was not significantly different, and 87.5 percent of patients had stage III/IV disease. The median followup was 26.3 months. The authors found that for patients with p16+ tumors, p16– tumors, and the overall cohort, the actuarial three-year locoregional progression-free survival rates were 97.8 percent, 73.5 percent, and 90.5 percent, respectively (P=0.006). The disease-free survival rates were 88.2 percent, 61.4 percent, and 81.7 percent, respectively (P=0.004). Patients with p16+ tumors had an 89.5 percent and 87.5 percent pathologic complete response on neck dissection with and without chemotherapy, respectively. In contrast, patients with p16– tumors had a 66.7 percent and 25 percent pathologic complete response on neck dissection with and without chemotherapy, respectively. The authors concluded that in this series, p16 status was found to be a significant predictive biomarker, and patients with p16+ tumors had much better outcomes than patients with p16– tumors. Further investigation is warranted to determine if less intense therapy is appropriate for select patients with p16+ OPSCC and if more aggressive strategies are needed to improve outcomes in patients with p16– disease.

Shoushtari A, Meeneghan M, Sheng K, et al. Intensity-modulated radiotherapy outcomes for oropharyngeal squamous cell carcinoma patients stratified by p16 status. Cancer. 2010;116(11):2645–2654.

Correspondence: Dr. Paul W. Read at pwr3u@hscmail.mcc.virginia.edu
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Longitudinal outcome study of sessile serrated adenomas of the colorectum Longitudinal outcome study of sessile serrated adenomas of the colorectum

Sessile serrated adenomas are associated with colorectal carcinomas that demonstrate high microsatellite instability. They are managed clinically in a similar fashion to adenomatous polyps. The authors studied the natural history of sessile serrated adenoma (SSA) by analyzing the outcome of previously undiagnosed SSAs and comparing their findings with those for hyperplastic polyps and adenomatous polyps. Colorectal polyps diagnosed between 1980 and 2001 as hyperplastic polyps were selected for study. Polyps identified as possible SSAs were reviewed by three pathologists and the diagnosis confirmed. Clinical followup was obtained for each SSA patient and matched with control hyperplastic polyp and adenomatous polyp patients. In total, 1,402 colorectal polyps diagnosed as hyperplastic polyps were examined, and 81 polyps in 55 patients (5.8 percent) were rediagnosed as SSA. Of these, 40 SSA patients had no previous history of colorectal carcinomas or adenomatous polyps with high-grade dysplasia (HGD). Of these 40 patients, five developed subsequent colorectal carcinomas and one developed adenomatous polyps with HGD. The incidence of subsequent colorectal carcinomas was significantly higher in SSA patients than in control patients with hyperplastic polyps (12.5 versus 1.8 percent) and adenomatous polyps (12.5 versus 1.8 percent). All of the subsequent colorectal carcinomas or adenomatous polyps with HGD developed in the proximal colon. Four of the five colorectal carcinomas demonstrated a high microsatellite instability phenotype. The authors concluded that SSAs are high-risk lesions, with 15 percent of the SSA patients developing subsequent colorectal carcinomas or adenomatous polyps with HGD. This incidence is higher than that for the control hyperplastic polyp and adenomatous polyp patients and supports close endoscopic followup in patients harboring SSAs.

Lu FI, van Niekerk de W, Owen D, et al. Longitudinal outcome study of sessile serrated adenomas of the colorectum: an increased risk for subsequent right-sided colorectal carcinoma. Am J Surg Pathol. 2010;34(7):927–934.

Correspondence: Fang-I Lu at fangilu@interchange.ubc.ca
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Expression of androgen receptor in breast cancer Expression of androgen receptor in breast cancer

Androgens exert growth inhibitory effects on estrogen receptor and progesterone receptor-negative breast cancer cell lines that show andro-gen receptor expression. These laboratory findings may be translated into inexpensive alternative therapies for hormone receptor-negative invasive breast cancers. The authors conducted a study to systematically evaluate androgen receptor expression by immunohistochemistry in invasive breast cancers. They analyzed androgen receptor (clone AR441, Dako) expression in 189 well-characterized consecutive invasive breast carcinomas represented with threefold redundancy on tissue microarrays. They semi-quantitated androgen receptor expression using a histochemical score-like method—a score of more than 10 was considered positive. Of the 189 consecutive invasive breast cancers, 151 (80 percent) were positive and 38 (20 percent) were negative for androgen receptor. The majority (95 percent) of estrogen receptor-positive tumors were also androgen receptor positive. Of the estrogen receptor-negative tumors, androgen receptor reactivity was seen in three of 30 (10 percent) triple-negative cases and five of eight (63 percent) estrogen receptor-negative/progesterone receptor-negative/HER2+ cases. Six of eight (75 percent) estrogen receptor-negative/androgen receptor-positive cases showed apocrine differentiation. Androgen receptor expression in estrogen receptor-positive cases was associated with smaller tumor size (P=0.0001), lower Nottingham grade (P=0.002), and less frequent tumor cell necrosis (P=0.0001). Androgen receptor expression in estrogen receptor-negative tumors was associated with lower Nottingham grade (P=0.005) and apocrine differentiation (P=0.039). The authors concluded that most estrogen receptor-positive breast tumors also express androgen receptor. Androgen receptor expression in estrogen receptor-negative/progesterone receptor-negative/HER2+ tumors, which commonly show apocrine differentiation, and in a subset of triple-negative apocrine tumors suggests that these tumors, together, comprise the molecular apocrine group described previously. However, these findings should be further confirmed on larger series of triple-negative and estrogen-negative/progesterone-negative/HER2+ tumors. Androgen receptor-targeted therapy in estrogen/progesterone re-ceptor-negative tumors may provide an inexpensive alternative to the usual high-dose chemotherapy with or without trastuzumab.

Niemeier LA, Dabbs DJ, Beriwal S, et al. Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol. 2010;23:205–212.

Correspondence: Dr. R. Bhargava at rbhargava@mail.magee.edu
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Analysis of lobular carcinoma in situ variants in breast cores Analysis of lobular carcinoma in situ variants in breast cores

Differentiating ductal carcinoma in situ from lobular carcinoma in situ on core biopsy has important clinical implications. Lobular carcinoma in situ variants, including lobular carcinoma in situ (LCIS) with necrosis and pleomorphic LCIS, share morphologic features with solid differentiating ductal carcinoma in situ (DCIS) that may lead to misclassification. The authors conducted a study to review all LCIS variants diagnosed in core biopsies at Northwestern University, Feinberg School of Medicine, Evanston, Ill., and determine the frequency of misinterpretation of variant LCIS as solid DCIS in archival core biopsies. They also sought to determine the frequency of upgrade to invasive carcinoma or DCIS in the surgical excision. Consecutive core biopsies with original diagnoses of predominantly solid DCIS without invasion that were performed between January 2001 and December 2005 at Northwestern University, Feinberg School of Medicine, were selected for E-cadherin staining. The revised diagnosis of LCIS was based on E-cadherin negativity and morphology. The frequency of LCIS variants being upgraded was then estimated from all core biopsies with original or revised diagnoses of pleomorphic LCIS or LCIS with necrosis. The authors found that among 75 cases of solid DCIS, 10 (13.3 percent) were reclassified as LCIS, including nine variants (five pleomorphic LCIS, four LCIS with necrosis) and one classic LCIS. Twenty-eight patients comprised the entire group of LCIS variant cases (both reclassified and originally diagnosed cases). Seven patients with LCIS variants (25 percent) were upgraded to invasive lobular carcinoma in surgical excision (four of 11 cases of LCIS with necrosis [36 percent] versus three of 17 cases of pleomorphic LCIS [18 percent]). The authors concluded that about one-tenth of solid DCIS diagnosed in core biopsies in the past may represent LCIS variants. These show a 25 percent upgrade to invasive lobular carcinoma in surgical excision. Distinguishing an LCIS variant from DCIS is important because of its implications for radiation therapy, although it may not affect surgical management.

Sullivan ME, Khan SA, Sullu Y, et al. Lobular carcinoma in situ variants in breast cores: potential for misdiagnosis, upgrade rates at surgical excision, and practical implications. Arch Pathol Lab Med. 2010;134(7):1024–1028.

Correspondence: Dr. Megan E. Sullivan at megan-sullivan@northwestern.edu
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Genomic and immunohistochemical analysis of adenosquamous carcinoma of the breast Genomic and immunohistochemical analysis of adenosquamous carcinoma of the breast

Breast adenosquamous carcinomas are rare tumors characterized by well-developed gland formation intimately admixed with solid nests of squamous cells immersed in a highly cellular spindle cell stroma. The medical literature has described a low-grade variant that is associated with a better prognosis. The authors studied five cases of adenosquamous carcinomas to determine their genetic profiles and to investigate whether the spindle cell component of these cancers could, at least in part, stem from the glandular/epithelial components. Five adenosquam-ous carcinomas of the breast were subjected to immunohistochemical analysis, microdissection and genetic analysis with a high-resolution microarray comparative genomic hybridization platform, and chromogenic in situ hybridization. All cases displayed a triple-negative immunophenotype, consistently expressed basal keratins, and showed variable levels of epidermal growth factor receptor expression. Microarray comparative genomic hybridization analysis of two of the cases revealed multiple low-level gains and losses affecting several chromosomal arms. Case one displayed gains of the whole of chromosome 7, and case two harbored a focal, high-level amplification of 7p12, encompassing the epidermal growth factor receptor gene, which was associated with strong and intense membranous epidermal growth factor receptor expression. Chromogenic in situ hybridization revealed that the genetic features found in the epithelial cells were also present in a minority of the spindle cells of the stromal component, in particular those near the epithelial clusters. This indicated that some of the spindle cells were clonal and derived from the epithelial component of the tumor. The authors concluded that breast adenosquamous carcinomas are triple-negative cancers that express basal keratins. These tumors harbor complex genetic profiles. Some of the spindle cells in adenosquamous carcinomas are derived from the epithelial component. This suggests that adenosquamous carcinomas may also be part of the group of metaplastic breast carcinomas with spindle cell metaplastic elements.

Geyer FC, Lambros MB, Natrajan R, et al. Genomic and immunohistochemical analysis of adenosquamous carcinoma of the breast. Mod Pathol. 2010;23:951–960.

Correspondence: Dr. J. S. Reis-Filho at jorge.reis-filho@icr.ac.uk and Dr. S. Badve at sbadve@iupui.edu
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Diagnostic utility of P504S/p63 cocktail, prostate-specific antigen, and prostatic acid phosphatase Diagnostic utility of P504S/p63 cocktail, prostate-specific antigen, and prostatic acid phosphatase

Seminal vesicle invasion by prostatic carcinoma is directly associated with tumor staging. Verification is challenging when the tumor demonstrates cribriform or papillary growth patterns or there are back-to-back small-gland proliferations. P504S is overexpressed in prostatic carcinoma and high-grade prostatic intraepithelial neoplasia with cytoplasmic immunoreactivity. P63 has positive immunoreactivity in basal cell nuclei of benign prostatic glands. Many researchers use a combination of these antibodies and their differing colors. The authors conducted a study to evaluate the usefulness of a single-color P504SS/p63 cocktail immunostain in verifying prostatic carcinoma within the seminal vesicle. Sections from 57 radical prostatectomy specimens of pathologic stage pT3b that contain seminal vesicle with prostatic carcinoma involvement were immunostained with primary antibodies against prostate-specific antigen (PSA) and prostatic acid phospha-tase (PAP) and a cocktail of antibodies against P504S and p63. The authors found that prostatic carcinoma cells from all 57 cases were diffusely positive for P504S, PSA, and PAP with cytoplasmic staining and no p63 nuclear staining. Seminal vesicle epithelium from all 57 cases was negative for all three markers with distinct p63 nuclear staining of the basal cells. Benign prostatic tissue was positive for PSA and PAP, as well as for p63, but negative for P504S. The authors concluded that the P504S/p63 one-color cocktail is a practical and cost-effective stain to differentiate prostatic carcinoma that involves the seminal vesicle from seminal vesicle epithelium. It is superior to PSA and PAP when sections contain seminal vesicle and benign glands because PSA and PAP cannot distinguish benign from malignant glands.

Harvey AM, Grice B, Hamilton C, et al. Diagnostic utility of P504S/p63 cocktail, prostate-specific antigen, and prostatic acid phosphatase in verifying prostatic carcinoma in-volvement in seminal vesicles: a study of 57 cases of radical prostatectomy specimens of pathologic stage pT3b. Arch Pathol Lab Med. 2010;134(7):983–988.

Correspondence: Dr. Qihui “Jim” Zhai at qihui.zhai@uc.edu
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.