College of American Pathologists
CAP Committees & Leadership CAP Calendar of Events Estore CAP Media Center CAP Foundation
 
About CAP    Career Center    Contact Us      
Search: Search
  [Advanced Search]  
 
CAP Home CAP Advocacy CAP Reference Resources and Publications CAP Education Programs CAP Accreditation and Laboratory Improvement CAP Members
CAP Home > CAP Reference Resources and Publications > CAP TODAY > CAP TODAY 2012 Archive > Anatomic Abstracts
Printable Version

  Anatomic Abstracts

 

 

 

 

August 2012

Editors:
Michael Cibull, MD
Thomas Cibull, MD
Rouzan Karabakhtsian, MD

Molecular markers and clinical behavior of uterine carcinosarcomas Molecular markers and clinical behavior of uterine carcinosarcomas

Carcinosarcomas (malignant mixed Müllerian tumors) of the uterus are rare and aggressive malignancies consisting of an epithelial (carcinoma) and a mesenchymal (sarcoma) tumor component. They are considered to be metaplastic endometrial carcinomas. The authors conducted a study in which they evaluated the molecular characteristics and clinical behavior of uterine carcinosarcomas to improve treatment regimens in the future. The immunohistochemical expression of estrogen receptor-α and -β progesterone receptor-A and -B, MLH1, MSH2, MSH6, PTEN (phosphatase and tensin homolog deleted on chromosome 10), p53, β-catenin, and cyclin D1 was determined in 40 uterine carcinosarcomas. Immunostaining was compared between epithelial and mesenchymal tumor components. To determine the role of the epithelial component in prognosis, clinicopathological data and survival rates were compared between patients with endometrioid and non-endometrioid epithelial tumor components. And to determine the prognosis of carcinosarcomas compared with high-risk endometrial carcinomas, clinicopathological characteristics and survival rates were compared between these patients. The authors found that hormone receptor expression occurred infrequently, with estrogen receptor-α in eight percent and –β in 32 percent, progesterone receptor-A in none and –B in 23 percent, next to β-catenin in four percent and cyclin D1 in seven percent. PTEN, MLH1, MSH2, and MSH6 mutations occurred in 39 percent, 33 percent, 22 percent, and 21 percent, respectively, based on absent immunostaining. Overexpression of p53 was observed in 38 percent. Expression patterns of p53, MSH2, and MSH6 corresponded between epithelial and mesenchymal tumor components. In this study cohort, the epithelial component caused the majority of metastases (72 percent) and vascular invasion (70 percent). Survival tended to be worse for patients with a non-endometrioid epithelial component than for those with an endometrioid epithelial component (five-year survival, 26 percent and 55 percent, respectively). Survival rates were also worse for patients with uterine carcinosarcomas compared with high-risk endometrial carcinomas (grade three endometrioid and non-endometrioid; five-year survival rates, 42 percent, 77 percent, and 57 percent, respectively). The authors concluded that these results support the monoclonal origin of uterine carcinosarcomas. The epithelial component determines prognosis by causing the majority of metastases and vascular invasion. To improve prognosis, treatment should focus on the epithelial tumor component of uterine carcinosarcomas.

De Jong RA, Nijman HW, Wijbrandi TF, et al. Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component. Mod Pathol. 2011;24:1368–1379.

Correspondence: R. A. de Jong at r.a.de.jong@og.umcg.nl
[ Top ]

Differentiation of small cell carcinoma from squamous cell carcinoma and other nonsmall cell carcinomas Differentiation of small cell carcinoma from squamous cell carcinoma and other nonsmall cell carcinomas

Small cell lung cancer comprises 14 percent of all lung cancers, and more than 30,000 new cases are diagnosed each year in the United States. It is one of the most distinctive malignancies in the field of oncology, with characteristic clinical properties, responsiveness to specific chemotherapies, and genetic features, and a highly reliable pathological diagnosis. Small cell lung cancer (SCLC) is defined by light microscopy, and a good quality hematoxylin and eosin-stained section is important. The vast majority of cases can be diagnosed using hematoxylin and eosin alone. However, in problem cases, immunohistochemistry can be very helpful in distinguishing SCLC from other tumors. Cytology is also a powerful tool, often being more definitive than small biopsies with scant tumor cells, crush artifact, or necrosis. Because virtually all SCLCs present in advanced stages, most patients are diagnosed based on small biopsy and cytology specimens. Historically, there has been significant evolution in the histological subclassification of SCLC dating from 1962, when Kreyberg proposed the oat cell and polygonal cell types. The current subclassification recognizes only two subtypes—pure SCLC and combined SCLC. The authors assert that pathologists need to do their best to make a diagnosis of SCLC or other histological types of lung cancer, and this can be achieved in most cases.

Travis WD. Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas. Mod Pathol. 2012;25:S18–S30.

Correspondence: Dr. W. D. Travis at travisw@mskcc.org
[ Top ]

Clinicopathologic spectrum of benign masses of vocal fold due to vocal abuse Clinicopathologic spectrum of benign masses of vocal fold due to vocal abuse

Benign masses of the vocal fold related to phonotrauma are clinically classified into polyps, nodules, Reinke’s edema, and cysts. Despite the distinctiveness of the clinical nomenclature, low inter- and intraobserver diagnostic agreement has been reported. With the exception of cysts, which are epithelial lined, histologic examination of the lesions has shown a variety of overlapping features insufficiently specific for clinical diagnosis. The authors conducted a study in which they reviewed clinicopathologic characteristics among these benign lesions of the vocal fold. Two pathologists analyzed 78 nonneoplastic lesions of the vocal fold for epithelial hyperplasia, basement membrane thickening, edema, vascular proliferation, and extracellular amyloid-like fibrin. In 46 cases with prebiopsy stroboscopic images, two otolaryngologists classified each lesion as polyp, nodule, Reinke’s edema, cyst, or other. They agreed in 43 percent of cases (n=20; 13 polyps, five nodules, one Reinke’s edema, one other) and disagreed in 57 percent (n=26). No histologic feature that reliably distinguished among the lesions was found. In addition, reactive stromal cell atypia was present in 14 cases. Cysts were distinctive because all were epithelial lined. The authors concluded that the clinicopathologic classification of benign laryngeal lesions is neither clinically reproducible nor histologically unique. Treatment will continue to be individualized based on clinical judgment.

Cipriani NA, Martin DE, Corey JP, et al. The clinicopathologic spectrum of benign mass lesions of the vocal fold due to vocal abuse. Int J Surg Pathol. 2011;19(5):583–587.

Correspondence: Dr. Nicole A. Cipriani at nicole.cipriani@uchospitals.edu
[ Top ]

Myxoid leiomyosarcoma of the uterus Myxoid leiomyosarcoma of the uterus

Recent guidelines have suggested that tumor cell necrosis, atypia, and mitotic index play a major role in distinguishing myxoid leiomyosarcomas (MLMSs) from myxoid leiomyomas. The authors conducted a study to focus on invasive growth pattern as a significant feature in this distinction in the absence of tumor cell necrosis. For the study, 12 uterine smooth muscle tumors with myxoid change in 60 percent or more of the lesion were interpreted as MLMS on the basis of focal mild atypia and one or more of the following: infiltrative growth pattern, vascular invasion, mitotic index of five or more mitotic figures/50 high-power fields, or a combination of at least focal severe atypia and at least two to four mitotic figures/50 high-power fields. Unequivocal tumor cell necrosis was not evident in any of the tumors. The various morphological features were correlated with outcome. With followup ranging from 19 to 113 months (mean, 60 months), five of the 12 women developed recurrences and two of them died. Nine of the 12 tumors had an infiltrative growth pattern, and all five recurrent tumors were from this group. The authors concluded that in the absence of tumor cell necrosis, an infiltrative margin is a major factor related to the potential for aggressive behavior of MLMS.

Burch DM, Tavassoli FA. Myxoid leiomyosarcoma of the uterus. Histopathology. 2011;59(6):1144–1155.

Correspondence: F. A. Tavassoli at fattaneh.tavassoli@yale.edu
[ Top ]

Myc amplification in postradiation cutaneous angiosarcoma after treatment of breast carcinoma Myc amplification in postradiation cutaneous angiosarcoma after treatment of breast carcinoma

Postradiation cutaneous vascular lesions after treatment of breast carcinoma comprise a heterogeneous group of benign, atypical, and malignant lesions and are best regarded as points along a morphological spectrum. The authors conducted a study in which they analyzed a series of cutaneous angiosarcomas after treatment of breast cancer in comparison with control cases and cases of atypical vascular lesions, with special emphasis on the expression and amplification of Myc. For the study, 66 cases were divided into control cases (five), cases in which a slight vascular proliferation was seen after radiotherapy of breast cancer (12), cases of atypical vascular lesions after radiotherapy (16), cases of postradiation cutaneous angiosarcomas (25), and cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (eight). Fluorescence in situ hybridization (FISH) did not show amplification of Myc in any of the control cases (two males and three females; 20 to 76 years); cases showing slight vascular proliferation, dermal fibrosis, and inflammation after radiotherapy of breast cancer (12 females; 48 to 79 years); cases of atypical vascular lesions after radiotherapy (16 females; 29 to 81 years); and cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (three males and five females; 25 to 92 years). In striking contrast, in all cases of postradiation cutaneous angiosarcoma (25 females; 46 to 95 years), Myc amplification was found by FISH in a variable number of counted nuclei. Immunohistochemically, strong positive nuclear staining for Myc and prox-1 was seen in cases of postradiation cutaneous angiosarcoma, whereas control cases and cases of atypical vascular proliferation after radiotherapy were negative for Myc and stained only focally positive for prox-1 in a number of cases. The authors concluded that Myc amplification represents an important additional diagnostic tool for distinguishing postradiation cutaneous angiosarcomas from atypical vascular lesions after radiotherapy. Immunohistochemical staining for Myc is useful for mapping these lesions and for careful tumor margin control.

Mentzel T, Schildhaus HU, Palmedo G, et al. Postradiation cutaneous angiosarcomas after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and control cases: clinicopathological, immunohistochemical and molecular analysis of 66 cases. Mod Pathol. 2012;25:75–85.

Correspondence: Dr. T. Mentzel at mentzel@dermpath.de or www.dermpath.de
[ Top ]

Identification of Gleason pattern five on prostatic needle core biopsy Identification of Gleason pattern five on prostatic needle core biopsy

The presence of a Gleason pattern five prostatic adenocarcinoma is associated with a worse outcome. The authors conducted a study in which they assessed the accuracy of grading a tumor as having Gleason pattern five and the potential factors contributing to its undergrading. From the consultation service of one of the authors, they identified 59 consecutive needle biopsy cases comprising 138 parts that, upon review, were graded as having Gleason pattern five. The final diagnosis for all cases was reported by an outside pathologist. The cases were sent for a second opinion at the request of clinicians or patients and not because the pathologist was seeking a second opinion. Considering the highest Gleason score in a given multi-core specimen as the overall Gleason score, Gleason pattern five was missed by the outside pathologist in 34 of 59 (57.6 percent) cases. Compared with the outside pathologist’s diagnosis, the Gleason score rendered at the second opinion was increased in 101 of 138 (73.2 percent) parts, decreased in five of 138 (3.6 percent) parts, and remained unchanged in 32 of 138 (23.2 percent) parts. Gleason pattern five was not identified by the initiating pathologist in 67 of 138 (48.6 percent) of the evaluated parts. The architectural patterns of pattern five were single cells (n=104; 75.3 percent), solid sheets (n=69; 50 percent), cords (n=62; 44.9 percent), and comedonecrosis (n=3; 2.2 percent). Pattern five was missed more frequently when it was not the primary pattern. The most common Gleason pattern five architectural type was single cells and the least common was comedonecrosis. None of the architectural patterns appeared to be more correctly identified than the others. However, the most accurate grading was when the primary pattern was five and was composed mostly of solid sheets. The authors concluded that owing to the important prognostic and therapeutic implications of Gleason pattern five, pathologists must be attuned to its varied patterns and to the fact that it may often represent a secondary or tertiary component of the carcinoma.

Fajardo DA, Miyamato H, Miller JS, et al. Identification of Gleason pattern 5 on prostatic needle core biopsy: frequency of underdiagnosis and relation to morphology. Am J Surg Pathol. 2011;35(11):1706–1711.

Correspondence: Dr. Jonathan I. Epstein at jepstein@jhmi.edu
[ Top ]

Use of classic and novel immunohistochemical markers in diagnosing cutaneous myeloid sarcoma Use of classic and novel immunohistochemical markers in diagnosing cutaneous myeloid sarcoma

Diagnosing cutaneous myeloid sarcoma based solely on histopathological features can be challenging. Although immunohistochemistry can aid in the diagnosis, specific markers have not been clearly identified. The authors evaluated the utility of immunohistochemical markers in 57 cutaneous myeloid sarcoma cases. In addition to the classical markers of CD117, CD163, CD34, myeloperoxidase, and lysozyme, they used CD33 and CD14, which are recently described markers in paraffin-embedded tissue samples, and Kruppel-like factor 4 (KLF-4), a novel monocytic marker. The authors’ results showed that lysozyme was expressed in 91 percent of cases, CD33 in 60 percent, myeloperoxidase in 54 percent, CD34 in 39 percent, and CD117 in 36 percent. An antibody panel that included lysozyme, CD117, and CD33 identified all cases. The monocytic markers CD14, KLF-4, and CD163 were expressed in 60 percent, 58 percent, and 40 percent of all cases, respectively. CD14 and KLF-4 expression was significantly more common in cases with monocytic differentiation. CD14 is the most sensitive and specific marker for monocytic differentiation (79 percent and 80 percent). Although KLF-4 in isolation is relatively insensitive (50 percent and 87 percent), it enhances sensitivity in detecting monocytic cutaneous myeloid sarcoma when combined with CD14. The authors believe their results indicate that in addition to classical immunohistochemical markers, targeted use of newer antibodies, including CD33, CD14, and KLF-4, is useful in diagnosing cutaneous myeloid sarcoma and detecting monocytic differentiation.

Ortiz C, Hurley MY, Ghahramani GK, et al. Use of classic and novel immunohistochemical markers in the diagnosis of cutaneous myeloid sarcoma. J Cutan Pathol. 2011;38:945–953.

Correspondence: Dr. John L. Frater at jfrater@path.wustl.edu
[ Top ]


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, assistant professor of pathology and laboratory medicine, University of Kentucky College of Medicine; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.
 
 
 © 2014 College of American Pathologists. All rights reserved. | Terms and Conditions | CAP ConnectFollow Us on FacebookFollow Us on LinkedInFollow Us on TwitterFollow Us on YouTubeFollow Us on FlickrSubscribe to a CAP RSS Feed