Anatomic Abstracts
| Anatomic Abstracts |
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July 2010 Editors:
To gain insight into prognosis, the authors investigated seven cases of post-chemotherapy retroperitoneal lymph-node dissections from patients with testicular germ-cell tumors that contained sizable nodules of differentiated skeletal muscle but that lacked a primitive cellular component and mitotic activity. The patients were 18 to 28 years old at the time of retroperitoneal lymph-node dissection. All had a previous nonseminomatous germ-cell tumor of the testis, five of which had a teratoma component. In one, the testicular tumor had foci of embryonal rhabdomyosarcoma. The retroperitoneal lymph-node dissections were performed 0.2 to 4.7 years after orchiectomy, following cisplatin-based chemotherapy, and contained rhabdomyomatous tumors that ranged from 0.8 to 5 cm. These consisted of nodular to diffuse aggregates of fetal-type rhabdomyocytes with central to peripheral nuclei and abundant eosinophilic, fibrillary cytoplasm with occasional cross striations. Elongated myotubes with multiple nuclei in a common sarcoplasm occurred at least focally in all cases. Mild to moderate nuclear atypia, including nuclear enlargement and nucleolar prominence, was present, but mitotic activity, necrosis, and a primitive cellular component were absent. All but one retroperitoneal lymph-node dissection also contained other teratomatous elements. Followup in six patients showed three were disease-free at 2.2 to 3.4 years; two developed recurrent teratoma at 1.3 to 3.7 years; and a sixth developed recurrent teratoma at 0.5 and two years, followed at 17 years by progressive tumor with elevated α-fetoprotein. No patient with available followup developed progressive sarcoma. The authors concluded that rhabdomyomatous tumors in retroperitoneal lymph-node dissection specimens after chemotherapy for metastatic testicular germ-cell tumors show clinical behavior similar to teratoma rather than rhabdomyosarcoma. The most likely explanation for the finding of pure rhabdomyomatous tumors in this setting, a phenomenon sometimes termed cytodifferentiation, is selective persistence of differentiated tumor cells due to chemotherapy. Clevenger JA, Foster RS, Ulbright TM. Differentiated rhabdomyomatous tumors after chemotherapy for metastatic testicular germ-cell tumors: a clinicopathological study of seven cases mandating separation from rhabdomyosarcoma. Mod Pathol. 2009;22(10):1361–1366. Correspondence: Dr. T. M. Ulbright at tulbrigh@iupui.edu
Adequate nodal staging of colon cancer has been defined as pathologic examination of at least 12 lymph nodes. The authors sought to refine this definition by quantifying the likelihood that a pathologically node-negative patient has no positive nodes. They identified from the Surveillance, Epidemiology and End Results (SEER) database patients with stage I–III adenocarcinoma of the colon between 1994 and 2005 who had at least one lymph node examined pathologically. The authors estimated the sensitivity of the pathologic staging of locoregional spread using a β-binomial model and developed the nodal staging score (NSS), which is the probability that a patient is staged correctly as node negative. NSS is a function of T stage and the number of nodes examined. The authors found that the probability of missing a positive node was 29.7 percent if five nodes were examined, 20 percent for eight nodes, and 13.6 percent for 12 nodes. An NSS of 90 percent could be achieved by examining a single node for T1 tumors and four nodes for T2 tumors. To maintain similar levels of NSS for T3 tumors, 13 nodes would need to be examined. Twenty-one nodes would need to be examined for T4 lesions. The authors concluded that the minimum number of examined nodes for adequate staging depends on the T stage. The score developed by the authors indicates the adequacy of nodal staging for patients with no positive nodes and can assist clinical decisionmaking in patients without nodal metastases. Gönen M, Schrag D, Weiser MR. Nodal staging score: a tool to assess adequate staging of node-negative colon cancer. J Clin Oncol. 2009;27(36):6166–6171. Correspondence: Dr. Mithat Gönen at gonenm@mskcc.org
The CD117 (KIT) protein is overexpressed in many human neoplasms, including adenoid cystic carcinoma of salivary glands. To evaluate the function of c-kit–activating mutations in adenoid cystic carcinoma of the salivary gland, the authors studied 14 cases (13 primary and one cervical lymph node metastasis) from their institution. They evaluated KIT protein expression by immunohistochemistry using formalin-fixed, paraffin-embedded tissue. Mutational analyses of c-kit extracellular (exon 9), juxtamembrane (exon 11), and tyrosine kinase domains (exons 13 and 17) were performed by polymerase chain-reaction, clonal selection, and DNA sequencing. All 14 cases demonstrated strong KIT expression by immunohistochemistry. Molecular analysis was successful in eight of 14 cases, and c-kit missense point mutations were detected in seven of eight cases (88 percent), including seven in exon 11, two in exon 9, two in exon 13, and two in exon 17. Eight silent point mutations were detected in five cases. Two cases contained missense mutations in more than one exon. The authors found different mutations in the primary tumor and the cervical lymph node metastasis of one patient. They detected point mutations in domains similar to those described in gastrointestinal stromal tumors, including Pro551Leu and Lys558Glu (5’ end of exon 11), Leu576Phe (3’ end of exon 11), Val643Ala (exon 13), and Asn822Ser (exon 17). The authors also identified additional novel point mutations in exons 9, 11, 13, and 17. Identification of such potential gain-of-function mutations in exon 11, and less frequently in exons 9, 13, and 17, suggests that KIT may be involved in the pathogenesis of adenoid cystic carcinoma of salivary glands. The authors concluded that their study raises a prospect of correlation of c-kit mutation and a potential treatment of adenoid cystic carcinoma with tyrosine kinase inhibitor (imatinib). Vila L, Liu H, Al-Quran SZ, et al. Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. Mod Pathol. 2009;22(10):1296–1302. Correspondence: Dr. C. Liu at liu@pathology.ufl.edu
Carney triad, as originally described in 1977, was the association of three tumors: gastric epithelioid leiomyosarcoma (later renamed gastrointestinal stromal tumor [GIST]), extra-adrenal paraganglioma, and pulmonary chondroma. The disorder primarily affects young women and is not familial. The authors studied the clinical and pathologic features of the gastric neoplasm in 104 patients with the syndrome. Most (88 percent) were young women (mean age, 22 years), and the usual presentation was gastric bleeding. The tumors, commonly antral based (61 percent), were multifocal and ranged from 0.2 to 18 cm in dimension. Most (86 percent) featured round and polygonal (epithelioid) cells. Metastasis occurred in 49 patients (47 percent) and involved gastric lymph nodes (29 percent), liver (25 percent), and peritoneum (13 percent). Immunopositivity was detected in the tumors tested as follows: KIT, 100 percent; CD34, 75 percent; PKCtheta, 21 percent; PDGFRA, 90 percent; and smooth muscle actin, six percent. Fourteen patients (13 percent) died of metastatic GIST at a mean age of 45 years (range, 30 to 69 years). Estimated 10- and 40-year survival rates were 100 percent and 73 percent, respectively. Median survival time was 26.5 years (range, 16 to 60 years). No correlation was found between National Institutes of Health tumor risk classification and tumor behavior. Compared with sporadic gastric GISTs, the gastric stromal tumor in Carney triad showed distinctive features: female predilection, young patient age, epithelioid cell predominance, multifocality, frequent lymph node metastasis, serial tumor occurrence, and unpredictable behavior. Therefore, the authors concluded that the Carney triad gastric stromal tumor is different from sporadic gastric GIST clinically, pathologically, and behaviorally. Zhang L, Smyrk TC, Young WF Jr., et al. Gastric stromal tumors in Carney triad are different clinically, pathologically, and behaviorally from sporadic gastric gastrointestinal stromal tumors: findings in 104 cases. Am J Surg Pathol. 2010;34(1):53–64. Correspondence: Dr. J. Aidan Carney at carney.aidan@mayo.edu
The margin status of lumpectomy specimens is related to frequency of local recurrence. Optimal surgical technique requires microscopic margins free of carcinoma by at least 2 mm. Recurrence following lumpectomy is associated with residual carcinoma secondary to inadequate resection. The authors reviewed a series of breast excisions to determine the frequency of residual carcinoma for positive, close, and negative margins. They reviewed 123 lumpectomies and excisional biopsies of invasive ductal carcinoma that had re-excisions. The margin status of specimens was recorded as positive, less than 1 mm, 1 to 2 mm, or greater than 2 mm. Residual invasive carcinoma was found in 44 percent (17), 25 percent (6), 28 percent (8), and 16 percent (5) of cases with positive, less than 1 mm, 1 to 2 mm, and greater than 2 mm margins, respectively. Residual invasive carcinomas were found in 57 percent (8), 100 percent (5), 67 percent (2), and 100 percent (2) of mastectomies with positive, less than 1 mm, 1 to 2 mm, and greater than 2 mm margins, respectively, in the initial lumpectomy or excisional biopsy. The authors concluded that the frequency of residual invasive carcinoma was related to the margin status of the original lumpectomy or biopsy. Even when margins were positive, most re-excisions were free of carcinoma. Residual invasive carcinoma was found in more than 25 percent of patients with margins of less than 2 mm, supporting re-excision for patients with margins of less than 2 mm. Sixteen percent of cases with margins greater than 2 mm harbored residual invasive carcinoma. Evaluation of margin status was complicated by tissue distortion and fragmentation. Skripenova S, Layfield LJ. Initial margin status for invasive ductal carcinoma of the breast and subsequent identification of carcinoma in reexcision specimens. Arch Pathol Lab Med. 2010;134(1):109–114. Correspondence: Dr. Lester J. Layfield at layfiel@aruplab.com
Diagnosis of Hirschsprung disease is based on the histopathological analysis of suction rectal biopsies. The authors conducted a study to assess the diagnostic value of calretinin immunohistochemistry as a simple and reliable method for diagnosing Hirsch-sprung disease (HD). They retrieved 131 initial rectal biopsies obtained for suspicion of HD in children. Calretinin immunohistochemistry was carried out on paraffin-embedded biopsies. The authors made a diagnosis of HD when no staining was observed. The results were analyzed statistically in comparison with the authors’ standard method of histology and acetylcholinesterase staining. The authors accurately diagnosed 130 biopsies on the basis of the positivity or negativity of calretinin staining. The senior pathologists diagnosed all cases of HD with no false positives. Furthermore, 12 additional cases initially considered to be doubtful for HD using the standard method were accurately diagnosed using calretinin immunohistochemistry. The false negative was a case of HD with a calretinin-positive biopsy. The authors also demonstrated the ease of calretinin interpretation compared with acetylcholinesterase for the junior pathologist. The authors concluded that calretinin immunohistochemistry overcomes most of the difficulties encountered using the combination of histology and acetylcholinesterase staining and detects almost all cases of HD with confidence, with no false positives. Therefore, the authors concluded that calretinin has advantages as a substitute for acetylcholinesterase. Guinard-Samuel V, Bonnard A, De Lagausie P, et al. Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease. Mod Pathol. 2009;22:1379–1384. Correspondence: Dr. D. Berrebi-Binczak at dominique.berrebi@rdb.ap-hop-paris.fr
CK19 and CD10 are useful markers in the differential diagnosis of pancreatic tumors. The authors evaluated CK19 and CD10 expression in pancreatic neuroendocrine tumors obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). They retrospectively studied 28 patients diagnosed with pancreatic neuroendocrine tumors based on EUS-FNA cytology (2004–2007) for immunohistochemical expression of CK19 and CD10. Immunohistochemistry was performed on cell blocks for each case. The authors noted the pattern of expression for CD10 (cytoplasmic or membranous) and its intensity (0–2). The staining of the stromal elements for CD10 was recorded as negative. Cytoplasmic staining in tumor cells and percentage distribution (1+ to 4+) for CK19 were regarded as positive. The authors found that 23 of 28 neuroendocrine tumors (82.14 percent) showed positive cytoplasmic or membranous staining, or both, for CD10, and 25 of 28 cases (89.29 percent) were positive for CK19. The authors concluded that the findings demonstrate the high expression of CD10 and CK19 in pancreatic neuroendocrine tumors. This indicates that CD10 and CK19 cannot reliably differentiate neuroendocrine tumors from other tumors with similar cytomorphologic features, such as solid pseudopapillary tumors, which frequently stain with CD10, and pancreatic adenocarcinoma, which stains with CK19. Salla C, Konstantinou P, Chatzipantelis P. CK19 and CD10 expression in pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound-guided fine-needle aspiration cytology. Cancer Cytopathol. 2009;117(6):516–521. Correspondence: Dr. Paschalis Chatzipantelis at pchatzipantelis@yahoo.com 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. |
