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  Anatomic Abstracts

 

 

 

 

March 2009

Editors:
Michael Cibull, MD
Melissa Kesler, MD

Percentage of high-grade carcinoma as a prognostic indicator for renal cell carcinoma
Relevance of TNM classification for upper gastroenteropancreatic neuroendocrine tumors
Prevalence of bone marrow involvement in systemic anaplastic large cell lymphoma
Use of Mash1 for differentiating pulmonary small cell carcinoma from Merkel cell carcinoma
Prognostic impact of dedifferentiation in retroperitoneal liposarcoma
Localized and disseminated neoplasms in lymphomas involving the breast

Percentage of high-grade carcinoma as a prognostic indicator for renal cell carcinoma Percentage of high-grade carcinoma as a prognostic indicator for renal cell carcinoma

The prognostic value of Fuhrman nuclear grade for patients with renal cell carcinoma has been well characterized. However, to the authors’ knowledge, the prognostic significance of amount of high-grade renal cell carcinoma has not been analyzed. To this end, the authors studied 898 consecutive renal cell carcinoma cases treated with nephrectomy between 1989 and 2003. Histopathologic features that were captured based on re-review of all slides included histologic type, pathologic stage, conventional Fuhrman grade, and percentage of Fuhrman grade 3 and 4 carcinoma as ascertained by visual inspection of histologic slides. The clinical endpoints were metastasis-free survival, cancer-specific survival, and overall survival. Kaplan-Meier analysis demonstrated that conventional Fuhrman grading and percentage of Fuhrman grade 3 and 4 carcinoma were highly correlated with all three measures of patient survival (P<.0001). Three categories of percentage of Fuhrman grade 3 and 4 carcinoma—zero percent, one percent to 50 percent, and 51 percent to 100 percent—were created and generated distinctly separate survival curves. On Cox proportional hazards multivariate analysis, TNM stage, tumor size, and percentage of Fuhrman grade 3 and 4 carcinoma were found to be significantly associated with all three types of patient survival (all P values <.05). The authors concluded that determination of the percentage of renal cell carcinoma that is zero percent, one percent to 50 percent, or 51 percent to 100 percent high Fuhrman grade 3 and 4 is a simple and powerful measurement of patient outcome after surgery that provides additional prognostic information beyond stage, tumor size, and conventional Fuhrman grade. This prognostic information could be useful for stratifying patients into prognostic groups for the development of more individualized follow-up schedules and enrollment in clinical trials.

Serrano MF, Katz M, Yan Y, et al. Percentage of high-grade carcinoma as a prognostic indicator in patients with renal cell carcinoma. Cancer. 2008;133:477–483.

Correspondence: Dr. Peter A. Humphrey at humphrey@path.wustl.edu
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Relevance of TNM classification for upper gastroenteropancreatic neuroendocrine tumors Relevance of TNM classification for upper gastroenteropancreatic neuroendocrine tumors

Neuroendocrine tumors of the gastroenteropancreatic system are a rare and challenging group of malignant neoplasms that can occur anywhere in the gastroenteropancreatic system. In 2006, a new tumornodemetastasis (TNM) classification system was proposed for staging and grading upper gastroenteropancreatic neuroendocrine tumors (NETs). The prognostic relevance of the TNM classification system was analyzed retrospectively in 202 patients from a referral center using histologically proven foregut NET. Patients were classified according to previous classification systems and the TNM classification. Survival data were acquired and statistical analyses were performed using log-rank and Cox regression analysis testing. Primary tumors were gastric (n=48), duodenal (n=23), and pancreatic (n=131). During the observation period, 21 percent of patients died. The overall five- and 10-year survival rates were 75 percent and 64 percent, respectively. Previous classification systems discriminated between low-grade and high-grade malignant NETs but did not allow further prognostic differentiation. In contrast, the proposed TNM classification was able to differentiate significantly between different tumor stages (stages I to III versus stage IV, P<.01) and cellular proliferation rates according to Ki-67 labeling (grade 1 versus grade 2, P=.04; grade 1 versus grade 3 and grade 2 versus grade 3, P<.01). Cox regression analysis confirmed an increased risk of reduced survival for patients with stage III or IV NET and grade 2 or 3 NET. The authors concluded that this study demonstrates the prognostic relevance of the newly proposed TNM classification system for foregut NETs with statistical significance for the subgroups of the staging classification and grading system. Therefore the new classification system provides a valid and powerful tool for prognostic stratification of gastroenteropancreatic NETs in clinical practice and research.

Pape UF, Jann H, Müller-Nordhorn J, et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer. 2008;113:256–265.

Correspondence: Dr. Ulrich-Frank Pape at ulrich-frank.pape@charite.de
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Prevalence of bone marrow involvement in systemic anaplastic large cell lymphoma Prevalence of bone marrow involvement in systemic anaplastic large cell lymphoma

The medical literature are inconsistent in their reporting of the frequency of bone marrow involvement in anaplastic large cell lymphoma. A prior study found that anaplastic large cell lymphoma involvement of bone marrow often was not evident on routine stains and advocated using immunohistochemical studies. The authors conducted a study in which they evaluated 70 bone marrow biopsies from 41 patients with anaplastic large cell lymphoma. They found 10 morphologically involved cases (14 percent of all biopsies, 22 percent of all patients). In most cases (90 percent), the involvement of bone marrow by anaplastic large cell lymphoma was massive and, therefore, evident on hematoxylin-and-eosin sections. In only one biopsy (one percent of all biopsies, two percent of all patients), the involvement was minimal and more difficult to detect. To determine if hematoxylin-and-eosin evaluation missed bone marrow involvement, the authors used a panel of antibodies, including CD30, ALK-1, epithelial membrane antigen, and granzyme. Only the 10 morphologically involved cases showed anaplastic large cell lymphoma cells with distinct CD30 expression. Other stains highlighted only a subset of the CD30-positive cases. Clinical followup was available for 30 patients and correlated marrow involvement with lower overall survival (P=.033). The authors concluded that, overall, marrow involvement in anaplastic large cell lymphoma is relatively uncommon and, when present, is identified on hematoxylin-and-eosin sections.

Weinberg OK, Seo K, Arber DA. Prevalence of bone marrow involvement in systemic anaplastic large cell lymphoma: Are immunohistochemical studies necessary? Hum Pathol. 2008;39:1331–1340.

Correspondence: Dr. Olga Weinberg, Stanford University, Dept. of Pathology, 300 Pasteur Drive, Stanford, CA 94305
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Use of Mash1 for differentiating pulmonary small cell carcinoma from Merkel cell carcinoma Use of Mash1 for differentiating pulmonary small cell carcinoma from Merkel cell carcinoma

Merkel cell carcinoma is the cutaneous counterpart of small cell carcinoma, and the most important differential diagnosis is cutaneous metastasis of small cell carcinoma of the lung. A handful of studies have reported on the utility of a variety of immunohistochemical markers that distinguish between the two entities. Achaetescute complex-like 1 (Mash1, ASCL1) is important in the development of the brain and diffuse neuroendocrine system, including pulmonary neuroendocrine cells. A recent study, using a cDNA array, identified Mash1 as one of the best classifier genes for differentiating pulmonary small cell carcinoma from Merkel cell carcinoma. The authors immunohistochemically applied this finding to the diagnostic setting. A total of 30 cases of Merkel cell carcinoma and 59 cases of small cell carcinoma of the lung were immunostained with anti-Mash1 and TTF-1 antibodies. Of 59 small cell carcinomas, 49 (83 percent) expressed Mash1 in nuclear staining and 43 (73 percent) expressed TTF-1 in nuclear staining. Mash1 was negative in all 30 Merkel cell carcinomas, whereas TTF-1 expression was seen in one of the 30 Merkel cell carcinomas (three percent). The authors concluded that Mash1 is a useful adjunct marker for differentiating small cell carcinoma of the lung from Merkel cell carcinoma.

Ralston J, Chiriboga L, Nonaka D. MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma. Mod Pathol. 2008;21:1357–1362.

Correspondence: Dr. D. Nonaka at daisuke.nonaka@med.nyu.edu
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Prognostic impact of dedifferentiation in retroperitoneal liposarcoma Prognostic impact of dedifferentiation in retroperitoneal liposarcoma

A series of patients with well-differentiated/dedifferentiated retroperitoneal liposarcoma was studied to evaluate the prognostic value of the presence, extension, and grade of the dedifferentiated component. Among 148 patients with retroperitoneal liposarcoma (RLS) who underwent surgery over 20 years, the authors retrieved data on patients who had localized well-differentiated/ dedifferentiated RLS. For their current analysis, the authors included patients only if they had primary disease or a first recurrence at initial presentation. The dedifferentiated component was graded according to National Federation of Centers for the Fight Against Cancer (FNCLCC) criteria, and the extension of the dedifferentiated component was described as a percentage. Univariate and multivariate analyses were carried out for local recurrence-free survival (LRFS), event-free survival, and disease-specific survival. Of 93 patients identified, 36 (39 percent) had well-differentiated RLS and 57 (61 percent) had dedifferentiated RLS. The median followup was 71 months (range, 28 to 132 months). Seven patients (7.5 percent) developed distant metastases, including five who had dedifferentiated RLS. The five-year disease-specific survival rate was 42 percent for patients with dedifferentiated RLS and 71.6 percent for those with well-differentiated RLS (P=.018). The corresponding rates for local recurrence-free survival were 22 percent and 43.3 percent, respectively (P=.007). The presence of the dedifferentiated component and its FNCLCC grade were independent prognostic factors for disease-specific survival and local recurrence-free survival. The administration of radiation therapy was associated indepen­dently with better local recurrence-free survival. The authors concluded that patients with high-grade dedifferentiated RLS had a worse prognosis in terms of disease-specific survival and local recurrence-free survival. The extension of the dedifferentiated component and its mitotic index were relevant for event-free survival. The results indicate that radiation therapy may improve local recurrence-free survival rates. These data may help stratify the risk of recurrence for patients with RLS. Clinical studies on new multimodality approaches are warranted.

Mussi C, Collini P, Miceli R, et al. The prognostic impact of dedifferentiation in retroperitoneal liposarcoma: a series of surgically treated patients at a single institution. Cancer. 2008;113:1657–1665.

Correspondence: Dr. Alessandro Gronchi at alessandro.gronchi@istitutotumori.mi.it
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Localized and disseminated neoplasms in lymphomas involving the breast Localized and disseminated neoplasms in lymphomas involving the breast

Lymphomas involving the breast account for approximately two percent of extranodal non-Hodgkin lymphomas and less than one percent of all non-Hodgkin lymphomas. The authors conducted a study to classify breast lymphomas using the World Health Organization classification and then compared this classification with clinical, histologic, and radiologic findings as well as survival. The study group included 106 patients with breast lymphoma (105 women and one man). The neoplasms were divided into localized disease (n=50) and disseminated disease (n=56) based on extent of disease at initial diagnosis. The follow-up period ranged from four to 252 months (median, 49 months). Almost all (97 percent) patients presented with a palpable breast mass or masses. In the localized group, diffuse large B-cell lymphoma (DLBCL) was most frequent (n=32; 64 percent). In the disseminated group, follicular lymphoma was most frequent and exclusive to this group (P=.0004). Mucosa-associated lymphoid tissue lymphomas occurred in both groups without a significant difference in frequency. A variety of other types of B-cell and T-cell non-Hodgkin lymphomas and classical Hodgkin lymphoma involved the breast at much lower frequency; most involved the breast as part of disseminated disease. The clinical presentation correlated with radiologic findings: localized lymphomas presented as solitary masses, whereas disseminated lymphomas commonly presented as multifocal masses. The authors noted a significant difference in the disease-free survival rates between patients with localized and disseminated DLBCL (P=.003). In the disseminated group, patients with DLBCL had worse disease-free survival rates than patients with mucosa-associated lymphoid tissue lymphoma or follicular lymphoma (P=.01).

Talwalkar SS, Miranda RN, Valbuena JR, et al. Lymphomas involving the breast: a study of 106 cases comparing localized and disseminated neoplasms. Am J Surg Pathol. 2008;32:1299–1309.

Correspondence: Dr. Jeffrey Medeiros, University of Texas M.D. Anderson Cancer Center, Dept. of Hematopathology, 1515 Holcombe Blvd., Box 72, Houston, TX 77030
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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.