College of American Pathologists
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  Anatomic Abstracts





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April 2003

Sentinel lymph node biopsy for problematic spitzoid melanocytic lesions
Spindle or epithelioid melanocytic proliferations, or both, that display overlapping histopathologic features of Spitz nevus and Spitz-like melanoma are diagnostically difficult and controversial melanocytic tumors. There are reports of such lesions metastasizing to regional lymph nodes, with a few widely disseminating, resulting in death. The authors reviewed clinical and histopathologic data on patients who were identified at the University of Michigan with atypical or borderline spitzoid melanocytic proliferations and who underwent sentinel lymph node (SLN) biopsy. Six male and 12 female patients, ages five to 32 years (mean, 16 years), had tumors ranging in thickness from 1.2 mm to 7.9 mm (mean, 3.5 mm). Atypical histologic features that were present most frequently included incomplete maturation (100 percent), deep dermal mitoses (89 percent), nuclear pleomorphism (56 percent), and focal sheet-like growth (56 percent). Eight of 18 patients (44 percent) had SLN metastasis and were offered adjuvant treatment. One of eight patients (13 percent) with SLN-positive results who underwent regional lymphadenectomy had one additional involved lymph node. All 18 patients were alive and well with no evidence of recurrent or metastatic disease after a followup of three to 42 months (mean, 12 months). The authors concluded that histologically atypical or borderline spitzoid, melanocytic tumors are diagnostically challenging and controversial melanocytic lesions, some of which represent unrecognized melanomas. SLN biopsy aids in confirming a diagnosis of melanoma and identifies patients who may benefit from early therapeutic lymph node dissection or adjuvant therapy, or both.

Su LD, Fullen DR, Sondak VK, et al. Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions. A report on 18 patients. Cancer. 2003;97: 499–507.

Reprints: Dr. Lyndon D. Su, Dept. of Pathology, Division of Dermatopathology, University of Michigan Medical Center, Medical Sciences I, M5224, 1301 Catherine St., Ann Arbor, MI 48109-0602;

Expression of cytokeratins 17 and 5/6 in aggressive breast carcinomas
Markers that offer prognostic information independent of other variables may help in guiding therapy and are particularly important in early stage carcinomas. In a study of 505 breast carcinomas (median followup, 63 months) analyzed by tissue microarray, expression of cytokeratin 17 or 5/6, or both, was a significant prognostic factor independent of tumor size, tumor grade, Her2/neu status, estrogen-receptor expression, and GATA-3 status in node-negative carcinomas. Further, no significant correlation was identified between the expression of these basal cytokeratins and Her2/neu expression. Ninety of the 564 tumors (16 percent) reacted with cytokeratin 17 or 5/6, or both. (Survival data were available for 505 cases.) In 245 patients with negative lymph nodes, the survival rate was lower for patients with tumors expressing these basal cytokeratins (P=0.006). Identification of this subset of aggressive breast carcinoma may help in making treatment decisions and designing therapies with a specific target.

Van de Rijn M, Perou CM, Tibshirani R, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol. 2002;161:1991–1996.

Reprints: Dr. Matt van de Rijn, L235 Dept. of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305;

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes
Numerous immunohistochemical stains have been used to detect metastatic melanoma in sentinel lymph node biopsies. HMB-45 is considered by some to be a specific tool to detect early metastatic melanoma. One or two isolated HMB-45-positive cells occasionally may cause complications in diagnostic interpretation. The authors conducted a study to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare it with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining were performed on 15 histologically negative SLNs excised from patients with malignant melanoma (group A) and 15 histologically negative SLNs excised from patients with breast carcinoma (group B). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all group B SLNs after blocking endogenous biotins. Electron microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in six of 15 SLNs removed for malignant melanoma; eight of 15 for breast carcinoma; and three of five cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in six of eight positive SLNs from group B. Anti-Melan A antibody was negative in all SLNs from group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for detecting micrometastasis of malignant melanoma and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.

Mahmood MN, Lee MW, Linden MD, et al. Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells. Mod Pathol. 2002; 15(12): 1228–1293.

Reprints: Dr. Muhammad N. Mahmood, Dept. of Pathology, Henry Ford Hospital, K-6, Clinic Building, 2799 W. Grand Blvd., Detroit, MI 48202;

Pathologic prion protein in the olfactory epithelium in sporadic CJD
It has been difficult to establish a definitive diagnosis of Creutzfeldt-Jakob disease without a brain biopsy. The olfactory cortexes and the olfactory tracts, however, are involved in sporadic Creutzfeldt-Jakob disease. The authors examined peripheral regions of the olfactory sensory pathway, including the olfactory mucosa, to assess whether pathologic infectious prion protein (PrPsc) is deposited in the epithelium lining the nasal cavity. They studied nine patients with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease from whom they obtained the brain, cribriform plate with the attached olfactory mucosa, and surrounding respiratory epithelium at autopsy. Control samples of nasal mucosa were obtained post mortem or at biopsy from age-matched control subjects and from control patients with other neurodegenerative diseases. The olfactory and respiratory mucosa and the intracranial olfactory system were analyzed by light microscopy, immunohistochemistry, and Western blotting for pathological changes and for deposition of PrPsc. In all nine patients with sporadic Creutzfeldt-Jakob disease, PrPsc was found in the olfactory cilia and central olfactory pathway but not in the respiratory mucosa. No PrPsc was detected in any of the tissue samples from the 11 controls. The authors’ pathological and biochemical studies showed that PrPsc is deposited in the neuroepithelium of the olfactory mucosa in patients with sporadic Creutzfeldt-Jakob disease, indicating that olfactory biopsy may provide diagnostic information in living patients. The olfactory pathway may represent a route of infection and a means of spreading prions.

Zanusso G, Ferrari S, Cardone F, et al. Detection of pathologic prion protein in the olfactory epithelium in sporadic Creutzfeldt-Jakob disease. N Engl J Med. 2003; 348: 711–719.

Reprints: Dr. S. Monaco, Section of Clinical Neurology, Dept. of Neurologic and Visual Sciences, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; salvatore. monaco@

Whipple resections in patients without malignancy
Whipple resections (pancreaticoduodenectomy) has evolved into a safe procedure to treat pancreatic adenocarcinoma and refractory chronic pancreatitis in major high-volume medical centers. Some Whipple resections performed for a clinical suspicion of malignancy, however, reveal only benign disease on pathologic examination. The authors evaluated the frequency of such Whipple resections without tumor in a large series of pancreaticoduodenectomies and classified the diverse pancreatic and biliary tract diseases present in these specimens. Of 442 Whipple resections performed from 1999 through 2001, 47 (10.6 percent) were negative for neoplastic disease and, in 40 cases, had been performed for a clinical suspicion of malignancy. Most Whipple resections revealed benign pancreatic disease, including eight (17 percent) cases of alcohol-associated chronic pancreatitis, four (8.5 percent) of gallstone-associated pancreatitis, one (2.1 percent) of pancreas divisum, six (12.8 percent) of “ordinary” chronic pancreatitis of unknown etiology, and 11 (23.4 percent) of lymphoplasmacytic sclerosing pancreatitis. Patients with lymphoplasmacytic sclerosing pancreatitis, in particular, were thought to harbor malignancy, whereas only 13 of 19 (68.4 percent) Whipple resections showing histologically ordinary forms of chronic pancreatitis were performed for a clinical suspicion of malignancy. Benign biliary tract disease, including three cases of primary sclerosing cholangitis, two cases of choledocholithiasis-associated chronic biliary tract disease, and four fibroinflammatory strictures isolated to the intrapancreatic common bile duct, was a common etiology for clinically suspicious Whipple resections (22.5 percent of cases). Pancreatic intraepithelial neoplasia (PanIN) was a common finding among all pancreata, whether involved by pancreatitis or histologically normal. Overall, PanIN 1A/1B was present in 68.1 percent, PanIN 2 in 40.4 percent, and PanIN 3 in 2.1 percent. These findings indicate that benign but clinically suspicious Whipple resections are relatively common in high-volume medical centers (9.2 percent) and reveal a diverse group of clinicopathologically distinctive pancreatic and biliary tract diseases.

Abraham SC, Wilentz RE, Yeo CJ, et al. Pancreaticoduodenectomy (Whipple resections) in patients without malignancy. Are they all ‘chronic pancreatitis’? Am J Surg Pathol. 2003;27(1):110–120.

Reprints: Dr. Susan C. Abraham, Dept. of Pathology, Hilton 11, Mayo Clinic, 220 First St., SW, Rochester, MN 55905; abraham. susan@ mayo.edun