College of American Pathologists
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  Anatomic Abstracts





March 2010

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

Lymph node ratio as a predictor of survival in melanoma patients Lymph node ratio as a predictor of survival in melanoma patients

The authors conducted an analysis in which they compared various measures associated with lymph node dissection and identified threshold values associated with disease-specific survival outcomes in patients with melanoma. Patients with lymph node-positive melanoma who underwent therapeutic lymph node dissection of the neck, axilla, and inguinal region were identified from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) database from 1998 to 2005. The authors performed Cox multivariate analyses to determine the impact on disease-specific survival (DSS) of the total number of lymph nodes removed, number of negative lymph nodes removed, and lymph node ratio. Multivariate cutpoint analyses were conducted for each anatomic region to identify the threshold values associated with the greatest improvement in DSS. The authors found that lymph node ratio was significantly associated with DSS for all node regions. The ratio thresholds resulting in the greatest difference in five-year DSS were 0.07, 0.13, and 0.18 for neck, axillary, and inguinal regions, respectively, corre-sponding to 15, 8, and 6 lymph nodes removed per positive lymph node. After adjusting for other clinicopathologic factors, the hazard ratios were 0.53 (95 percent confidence interval [CI], 0.40–0.71) in the neck, 0.52 (95 percent CI, 0.42–0.65) in the axillary, and 0.47 (95 percent CI, 0.36–0.61) in the inguinal regions for patients who met the lymph node ratio threshold. The authors concluded that of the prognostic factors exam-ined, lymph node ratio was the best indicator of the extent of node dissection, regardless of anatomic nodal region. These data provide evidencebased guidelines for defining adequate lymph node dissections in melanoma patients.

Xing Y, Badgwell BD, Ross MI, et al. Lymph node ratio predicts disease-specific survival in melanoma patients. Cancer. 2009;115(11):2505–2513.

Correspondence: Dr. Janice N. Cormier at
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Tissue floaters and contaminants in the histology laboratory Tissue floaters and contaminants in the histology laboratory

Anatomic pathology diagnoses are often based on morphologic features. Increased attention to patient safety has led to an emphasis on main-taining patient identity. Cross-contamination from one specimen to another is an example of a patient identity issue that can benefit from process improvement. The authors conducted a study to quantify cross-contamination from histology water baths and slide stainers. They tested for the presence of contaminants in water baths at cutting stations and in linear stainer stain baths. They assessed the potential for tissue discohesion and carryover in tissue samples and for carryover onto blank slides sent through the strainer. In the 13 water baths examined, which totaled 195 L of water, only one fragment of tissue was identified. However, the stain baths contained an abundance of tissue contaminants, ranging in size from two or three cells to hundreds of cells. The first sets of xylenes and alcohols were the most heavily contaminated. Cross-contamination to blank slides occurred at a rate of eight percent, with the highest frequency in the late afternoon. The authors concluded that cross-contamination can present a significant challenge in the histology laboratory. Although the histotechnologists’ water baths are not heavily contaminated, the stainer baths contain contaminating tissue fragments. And cross-contamination occurs on blank slides in an experimental setting.

Platt E, Sommer P, McDonald L, et al. Tissue floaters and contaminants in the histology laboratory. Arch Pathol Lab Med. 2009;133(6):973–978.

Correspondence: Dr. Jennifer Hunt at
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Link between tumor budding in invasive front of tumors and prognosis Link between tumor budding in invasive front of tumors and prognosis

Complete tumor regression is difficult to achieve in neoadjuvant chemotherapy for advanced esophageal cancers, and tumor often remains after chemotherapy. Furthermore, the best method for evaluating response to chemotherapy based on histopathologic examination of residual tumors has not been established. The authors conducted a study in which they examined the correlation between various histopathologic factors and clinical response with survival, including the impact of tumor budding in the invasive front of tumors on clinical response and survival. The study involved 74 patients who received neoadjuvant chemotherapy—5-fluorouracil, cisplatin, and doxorubicin—followed by surgery for advanced esophageal squamous cell carcinoma. Among the 74 patients, three achieved a pathologic complete response. Twenty-nine of 71 residual tumors (41 percent) demonstrated high-grade budding in the invasive front. The five-year survival rate for patients with low-grade budding tumors was 49 percent, compared with 17 percent for those with high-grade budding (P<.001). Budding correlated inversely with good response, which was observed in 44 of 74 patients (60 percent). Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding, and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor, followed by number of lymph node metastases. The authors concluded that tumor budding in the invasive front of tumors correlated significantly with the clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasive front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified.

Miyata H, Yoshioka A, Yamasaki M, et al. Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas re-ceiving neoadjuvant chemotherapy. Cancer. 2009;115(14):3324–3334.

Correspondence: Dr. Hiroshi Miyata at
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Criteria for enhancing detection of DNA mismatch repair deficiency Criteria for enhancing detection of DNA mismatch repair deficiency

Women with hereditary nonpolyposis colorectal cancer have a high risk for endometrial cancer and frequently present with a gynecologic cancer as their first or sentinel malignancy. It is important to identify these women given their personal and familial risk for synchronous and metachronous tumors. The revised Bethesda guidelines provide screening criteria for hereditary nonpolyposis colorectal cancer (HNPCC). However, no such screening recommendations exist for women with endometrial carcinoma. The authors applied some of the colorectal cancer screening criteria, including age and tumor morphology, to endometrial endometrioid carcinoma. They conducted a study to describe patient and tumor characteristics and to assess the ability of these criteria to enhance detection of mismatch repair (MMR) deficiency and, therefore, HNPCC in endometrial cancer. The authors performed immunohistochemistry for DNA mismatch repair (IHC-MMR) proteins in a defined subset of patients with endometrial cancer. This included women younger than 50 years of age and women 50 years or older whose tumors showed morphologic features suggestive of MMR deficiency (TM-MMR). The extent of IHC-MMR in the older patient group was compared with that in a comparison group with endometrial cancer who were 50 years or older and who were previously analyzed for microsatellite instability status. Seventy-one patients met the selection criteria for IHC testing; 32 (45 percent) showed abnormal results. The rate of IHC abnor-mality in the younger group was approximately 30 percent, and the group had nearly equal distribution of MLH1/PMS2 and MSH2/MSH6 ab-normalities. In the older age group, TM-MMR triggered IHC analysis in 31 of 34 cases. Of these, 18 cases (58 percent) showed loss of IHC-MMR, and seven had loss of MSH2/MSH6. In contrast, the rate of microsatellite instability in the comparison group was only 21 percent. The group with abnormal IHC showed more frequent tumor-infiltrating lymphocytes, dedifferentiated endometrial cancer, more tumors centered in the lower uterine segment, and more frequent synchronous clear cell carcinomas of the ovary than tumors with a normal immunophenotype. Although many of the patients (13 of 32) with loss of IHC-MMR showed personal or family history of HNPCC-associated tumors, or both, most did not. The authors concluded that tumor morphology along with IHC-MMR enhances the detection of endometrial cancer patients at risk of developing HNPCC.

Garg K, Leitao MM Jr, Kauff ND, et al. Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities. Am J Surg Pathol. 2009;33(6):925–933.

Correspondence: Dr. Robert A. Soslow at
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Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma

Invasive micropapillary carcinoma is generally an aggressive morphologic variant that has been described in the bladder, lung, breast, salivary gland, gastrointestinal tract, and ovary. Given the morphologic similarities between invasive micropapillary carcinomas (IMCs) arising from different organ systems and the high propensity of this histologic subtype for lymphatic metastasis, it may be necessary to use immunohistochemical (IHC) markers to determine the primary site of an IMC. Few studies have compared the IHC profiles of IMCs originating from different sites. The authors tested a panel of 11 IHC markers for their ability to distinguish urothelial, lung, breast, and ovarian IMC using a tissue microarray constructed from primary tumor tissue from 47 patients with IMC (13 bladder, 6 lung, 16 breast, and 12 ovary). For each tumor, classification as IMC was verified by reverse polarity MUC1 expression. The authors found that immunostaining for uroplakin, CK20, TTF-1, estrogen receptor, WT-1 and/or PAX8, and mammaglobin was the best panel for determining the most likely primary site of IMC. The best markers for identifying urothelial IMC were uroplakin and CK20—p63, high molecular weight cytokeratin, and thrombomodulin were less sensitive and specific. Lung IMC was uniformly TTF-1 positive. Breast IMC was estrogen-receptor positive, mammaglobin positive, and PAX8/WT-1 negative, while ovarian IMC was estrogen-receptor positive, mammaglobin negative, and PAX8/WT-1 positive. In the metastatic setting, or when IMC occurs without an associated in situ or conventional carcinoma component, staining for uroplakin, CK20, TTF-1, estrogen receptor, WT-1 and/or PAX8, and mammaglobin is the best panel for classifying the likely primary site of IMC.

Lotan TL, Ye H, Melamed J, et al. Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma. Am J Surg Pathol. 2009;33(7):1037–1041.

Correspondence: Dr. Jonathan I. Epstein at
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Prostate cancer with tertiary Gleason pattern 5 in prostate needle biopsy Prostate cancer with tertiary Gleason pattern 5 in prostate needle biopsy

The significance of tertiary Gleason pattern/grade 5 on prostatectomy has been studied, but its significance on biopsy remains uncertain. The authors conducted a study in which they examined the preoperative clinical and biopsy findings in 53 patients with biopsy tertiary pattern 5 and 119 patients with primary/secondary biopsy pattern 5. They compared prostatectomy findings and prostate-specific antigen (PSA) failure rates in patients treated surgically and cause-specific and all-cause mortality in patients treated nonsurgically. At presentation, age, gland volume, PSA, and biopsy cancer volume were similar in patients with tertiary and primary/secondary grade 5. Twenty patients underwent prostatectomy and 152 were treated nonsurgically. Regardless of pattern, patients treated by prostatectomy were younger (P=.003), had lower PSA levels (P=.001), and had less cancer on biopsy (P=.0001). Prostatectomy findings and PSA failures were not significantly different in patients with tertiary grade 5 versus primary/secondary pattern 5. In patients treated nonsurgically, those with primary pattern 5 compared with those with tertiary pattern 5 had a significantly higher risk of all-cause mortality (adjusted hazard ratio [HR], 2.33; 95 percent confidence inter-val [CI], 1.10–4.90; P=.026) and cause-specific mortality (adjusted HR, 7.52; 95 percent CI, 2.84–19.87; P<.001). In contrast, patients with secondary pattern 5 had a comparable all-cause mortality risk compared with patients with tertiary pattern 5 (adjusted HR, 1.04; 95 percent CI, 0.47–2.32; P=.92) but had a marginally higher risk of cause-specific mortality than patients with tertiary pattern 5 (adjusted HR, 2.13; 95 percent CI, 0.75–6.10; P=.16).

Trpkov K, Zhang J, Chan M, et al. Prostate cancer with tertiary Gleason pattern 5 in prostate needle biopsy: clinicopathologic findings and disease progression. Am J Surg Pathol. 2009;33(2):233–240.

Correspondence: Dr. Kiril Trpkov at
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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.