College of American Pathologists
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  Anatomic Abstracts





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March 2007

Michael Cibull, MD
Melissa Kesler, MD

Gastrointestinal involvement in mantle cell lymphoma
Natural history of urothelial inverted papilloma
Assessing breast cancer patients with brain metastases
Fine-needle aspiration cytology of Hodgkin’s lymphoma
Detecting continuous and skip-type intraductal cancer existence for IPMN

bullet Gastrointestinal involvement in mantle cell lymphoma

The frequency of gastrointestinal tract involvement in mantle cell lymphoma at diagnosis is reported to be below 30 percent. To further investigate the frequency of gastrointestinal involvement by mantle cell lymphoma (MCL), the authors prospectively performed upper and lower endoscopy on 13 untreated MCL patients at diagnosis. Multiple biopsies from endoscopically normal and abnormal gastric and colonic mucosa were studied with immunohistochemistry for CD20, CD5, and cyclin D1 and with fluorescence in situ hybridization (FISH) for t(11;14) and polymerase chain reaction (PCR) for immunoglobulin heavy chain gene. The authors identified abnormal mucosa in 38 percent of cases by upper endoscopy (mainly mild, nonspecific gastritis) and in 54 percent of cases by lower endoscopy (mostly micropolyps). Histologically, infiltration by MCL was demonstrated in the stomach in 77 percent of cases and in the colon in 77 percent of cases. Ninety-two percent of patients showed upper or lower gastrointestinal tract infiltration by MCL. Histologic evidence of MCL involvement was present in all cases with endoscopically abnormal mucosa, but it was also observed in two-thirds of cases with endoscopically unremarkable mucosa. Positive cyclin D1 immunohistochemistry was seen in all instances displaying CD20- and CD5-positive lymphoid infiltrates, whereas t(11;14) was demonstrated by FISH in 63.5 percent, and PCR was clonal in 64 percent of those instances. The authors concluded that the majority of MCL patients showed gastrointestinal tract involvement at diagnosis, not uncommonly in the form of minute lymphoid infiltrates. Immunohistochemistry for cyclin D1 was significantly more sensitive than FISH for t(11;14) or PCR for immunoglobulin heavy chain gene to confirm MCL in this setting.

Salar A, Juanpere N, Bellosillo B, et al. Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic, endoscopic, and pathologic study. Am J Surg Pathol. 2006;30(10):1274–1280.

Reprints: Dr. Antonio Salar, Dept. of Clinical Hematology, Hospital del Mar, Passeig Maritim 25-29 08003 Barcelona, Spain;

bullet Natural history of urothelial inverted papilloma

Inverted urothelial papilloma is an uncommon urothelial neoplasm. Although it is traditionally regarded as a benign tumor, conflicting data on multiplicity, recurrence rate, and association with urothelial carcinoma have led to uncertainties concerning its biologic behavior. The authors analyzed the clinicopathological characteristics of 75 cases of inverted papilloma in the urinary tract without prior or concurrent urothelial carcinoma to determine its biologic behavior and prognosis and to correlate these findings with surveillance strategies. The patients ranged in age from 26 to 85 years (mean, 60 years). Of the 46 patients for whom tobacco use history was available, 28 gave a history of smoking. Inverted papillomas were located in the urinary bladder (67 cases), prostatic urethra (four cases), and ureter (four cases). The majority of vesical tumors arose from the trigone or near the bladder neck. Common presenting complaints included hematuria, dysuria, and irritative voiding symptoms. One case of vesical inverted papilloma recurred. All other patients were free of tumor recurrence or progression during a mean followup of 68 months (range, two to 240 months). The authors concluded that the extremely low incidence of tumor recurrence (1%) and strikingly favorable prognosis suggest that inverted urothelial papilloma, when diagnosed according to strictly defined criteria, is a benign urothelial neoplasm not related to urothelial carcinoma. Therefore, complete transurethral resection of inverted papilloma is adequate surgical therapy, and surveillance protocols as rigorous as those employed in the management of urothelial carcinoma may not be necessary.

Sung MT, MacLennan GT, Lopez-Beltran A, et al. Natural history of urothelial inverted papilloma. Cancer. 2006;107:2622–2627.

Reprints: Dr. Liang Cheng, Dept. of Pathology and Laboratory Medicine, Indiana University School of Medicine, Clarian Pathology Laboratory, Room 4010, 350 W. 11th St., Indianapolis, IN 46202;

bullet Assessing breast cancer patients with brain metastases

Brain metastases from breast cancer are associated with significant morbidity and mortality. The authors of this study examined a cohort of breast cancer patients who developed brain metastases for clinical-pathologic features and predictive markers that identify this high-risk subgroup of patients at diagnosis. The authors used the primary tumors from 55 patients who developed brain mestastases to construct a tissue microarray. They recorded the clinical and pathologic features and stained the tissue microarray for estrogen receptor, human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, and epidermal growth factor receptor (EGFR) by immunohistochemistry. They then compared this cohort of patients to a group of 254 patients who remained free of metastases (67 months mean followup) and to a cohort of 40 patients who developed mixed visceral and bone metastatic disease without brain recurrence over a similar period. The authors found that breast cancer patients who developed brain metastases were more likely to be younger than 50 years old (P<0.001) and their primary tumors were more likely to be estrogen receptor negative (P<0.001) and high grade (P=0.002). The primary tumors were also more likely to express cytokeratin 5/6 (P<0.001) and EGFR (P=0.001) and to overexpress HER2. These data suggest a profile for breast cancer patients at increased risk for developing brain metastases. Predictive factors to help identify patients with metastatic breast cancer who are at an increased risk for developing central nervous system recurrence might permit screening this population to detect occult metastases at an earlier stage, when patients might be more amenable to treatment. In addition, this subset of patients may benefit from the development of prophylactic treatment regimens and novel targeted therapeutic strategies to prevent this devastating complication of breast cancer.

Hicks DG, Short SM, Prescott NL, et al. Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol. 2006;30:1097–1104.

Reprints: Dr. Robert J. Weil, Neurological Surgery and Brain Tumor Institute/ND40, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195;

bullet Fine-needle aspiration cytology of Hodgkin’s lymphoma

The authors assessed the diagnostic accuracy of fine-needle aspiration cytology in the diagnosis of Hodgkin’s lymphoma. They selected all cases in which a cytologic diagnosis of Hodgkin’s lymphoma (HL), suggestive of or suspicious for HL or with HL as the prime differential diagnosis, was offered on fine-needle aspiration cytology (FNAC). They correlated these cases with histopathologic followup. The authors excluded from the study cases of primary HL diagnosed on cytology but without histopathology. Histopathologic followup was available in 46 cases. Of these, 42 were correctly diagnosed as HL, and there was discordance in four cases, comprising three cases of non-HL (two T-cell-rich B-cell lymphoma [TCRBCL] and one anaplastic large-cell lymphoma) and one case of metastatic carcinoma. Overall accuracy was 91.3 percent. In 14 cases, the cytologic features were diagnostic of recurrence, so no histopathologic examination was done. No followup was available for the remaining 19 cases, which were excluded from the study. The authors concluded that FNAC is a useful, rapid, and accurate approach to the diagnosis of recurrent HL and most cases of primary HL. Because of morphologic similarities, it is difficult to differentiate HL from anaplastic large-cell lymphoma and TCRBCL on FNAC. It is advisable to request a histopathologic examination in all cases of primary HL.

Jogai S, Al-Jassar A, Dey P, et al. Fine-needle aspiration cytology of Hodgkin’s lymphoma: a cytohistologic correlation study from a cancer center in Kuwait. Acta Cytol. 2006;50(6):656–662.

Reprint information not available.

bullet Detecting continuous and skip-type intraductal cancer existence for IPMN

Intraductal papillary mucinous neoplasm is a recently discovered pancreatic tumor that has continuous or discontinuous (skip) lesions. Reports suggest a higher frequency of cancer recurrence in the remnant pancreas after surgical resection of intraductal papillary mucinous neoplasm (IPMN). It is, therefore, important to precisely detect intraductal cancer extension and skip lesions when resecting IPMN. The authors performed intraoperative histologic examination of the surgical margin and cytologic examination of the pancreatic juice from each pancreatic segment (head, body, or tail) on 43 IPMN patients. In addition to the pre-operatively planned resection, one or two pancreatic segments were resected if the pancreatic juice tested positive in cytology. When a surgical margin was positive but the cytology in the remaining segment was negative, a subsegment (2-cm slice in width) was resected until a negative margin was confirmed. Twenty-five patients (58%) demonstrated negative results in histology and cytology obtained from the segments that were not initially intended to be removed. In contrast to the preoperative estimation, five patients were found to have a positive surgical margin and negative cytology; five patients demonstrated a negative surgical margin and positive cytology; and eight patients demonstrated a positive surgical margin and positive cytology. Investigations of the resected specimens revealed that eight patients (19%) had skip lesions in addition to the main lesion. Logistic regression analysis revealed that patients with a dilated main pancreatic duct, or those with cancerous lesions in the main tumors, were at high risk for positive histology or cytology, or both. The authors concluded that using intraoperative frozen-section histology and pancreatic juice cytology, 18 out of 43 patients in the study (42%) required additional resection of the pancreas. A necessary and sufficient range of resection should be determined by intraoperative examination.

Eguchi H, Ishikawa O, Ohigashi H, et al. Role of intraoperative cytology combined with histology in detecting continuous and skip type intraductal cancer existence for intraductal papillary mucinous carcinoma of the pancreas. Cancer. 2006;107:2567–2575.

Reprints: Dr. Hidetoshi Eguchi, Dept. of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Highashinari-ku, Osaka 537-8511, Japan;

Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.