The lipid-poor hemangioma: an investigation into the behavior of the "atypical" hemangioma.

OBJECTIVE: Most vertebral hemangiomas contain high signal intensity on T1-weighted MRI images. Atypical vertebral hemangiomas, which are defined as showing low-signal intensity on T1-weighted images, have been described as lesions which are prone to aggressive behavior. This study was performed to assess behavior of atypical hemangiomas. MATERIALS AND METHODS: Thoracic and lumbar spine MRI reports for the year 2012 were reviewed for diagnosis of atypical hemangioma. Images were reviewed by two independent observers, and cases which showed atypical vertebral hemangioma, and had imaging or clinical follow-up, were included in our study. RESULTS: Thirty atypical hemangiomas which had follow-up data were identified out of 2784 thoracic and lumbar MR examinations performed during 2012 at a single institution. Imaging follow-up was available for 23 lesions (mean follow-up 32 months), while there was clinical follow-up for the remaining seven lesions (mean 43.6 months). Twenty-two lesions were stable on imaging, while one demonstrated significant growth over approximately 6 years, developing MRI signal characteristics of a typical hemangioma. Eleven lesions had CT scans showing typical features of hemangioma. Two of the index lesions could not be identified on follow-up CT examinations, which showed normal-appearing spines. The remaining seven lesions were followed clinically; none of the patients reported symptoms in the region of the index lesions. CONCLUSIONS: Atypical hemangiomas are uncommon lesions. The cases in our population did not show aggressive behavior. A more appropriate designation for these lesions may be lipid-poor hemangioma, to distinguish them from aggressive hemangiomas.

Impact on clinical follow-up of the Milan System for salivary gland cytology: A comparison with a traditional diagnostic classification.

INTRODUCTION: No universally accepted classification exists for salivary gland FNA. The proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers a uniform classification with management recommendations. We compared FNA diagnoses from a prior study with specific diagnoses with corresponding MSRSGC diagnoses. METHODS: One-hundred and sixty-four cases from a prior cytological study with histological follow-up were re-reviewed by one of the authors and assigned to one of the MSRSGC categories. The original and MSRSCG diagnoses were compared, as were follow-up recommendations. RESULTS: The MSRSGC system classified 29 specimens as non-diagnostic (seven histologically shown to be benign salivary gland, two non-mucinous cysts, 14 sialadenitis, one pleomorphic adenoma, one haemangioma, one lymphoma, one adenoid cystic carcinoma, one squamous carcinoma and one benign lymphoid proliferation). The original study diagnosed these lesions as: seven benign cysts, 15 benign salivary gland tissue, one benign neoplasm and two insufficient for diagnosis. In seven cases, MSRSGC disagreed with original diagnoses and surgical resection showed lesions where optimal follow-up was more consistent with original cytological diagnosis. In 10 cases with disagreement, the MSRSGC was associated with a more appropriate follow-up based on the surgical diagnosis. Malignancy risks for the Milan categories were: non-diagnostic (12%), non-neoplastic (5%), atypia of undetermined significance (19%), neoplasm, benign (5%), neoplasm (40%), suspicious for malignancy (60%) and malignant (93%). CONCLUSION: MSRSGC was comparable with the original reported diagnoses in the majority of cases. Both systems had high accuracy for distinguishing benign from malignant lesions and both were associated with appropriate follow-up in most cases.

Solitary fibrous tumor of the ischioanal fossa-a multidisciplinary approach to management with radiologic-pathologic correlation.

Solitary fibrous tumors are primary mesenchymal tumors, which may occur in any part of the body. Overall, these tumors are considered to have intermediate malignant potential with 5- and 10-year metastasis-free and overall disease-specific survival rates of 74% and 55%, and 89% and 73%, respectively (Demicco et al, 2012). Herein we present an unusual case of solitary fibrous tumors involving the ischioanal fossa in a 19-year-old woman with radiologic-pathologic correlation. This case was complicated by extensive tumor vascularity and was thus managed with preoperative embolization followed by en bloc surgical resection.

The Papanicolaou Society of Cytopathology classification for pulmonary specimens: an overview.

The Papanicolaou Society of Cytopathology has formulated guidelines for respiratory cytology which include a classification scheme. The recommended classification scheme is based on the expertise of the committee members, extensive review of the literature and feedback from presentations at national and international meetings. Each category of the classification system is closely defined and link to a known risk for malignancy. The classification contains six categories designated as: 1) Non-diagnostic; 2) Negative for Malignancy; 3) Atypical; 4) Neoplastic (Benign and low grade cancer); 5) Suspicious for Malignancy; and 6) Malignant.

Thyroid fine needle aspiration cytology: a review of the National Cancer Institute state of the science symposium.

In October 2007, the National Cancer Institute (NCI) of the United States sponsored a conference reviewing the state of the science of thyroid fine needle aspiration (FNA). Multiple issues were reviewed including pre-FNA requirements, training specifications, criteria for the selection of patients to undergo FNA, diagnostic categories and criteria, ancillary testing and post-FNA follow-up and treatment options. A summation of conclusions covering three of these topics, followed by a question and answer session, was subsequently presented at the 35th European Congress of Cytology (ECC) in Lisbon, Portugal in September of 2009. At the ECC, the findings of the NCI committee proposals regarding the indications for FNA of thyroid nodules, diagnostic categories and criteria, and post-FNA options for follow-up and treatment were discussed. Herein we review the presentations given at that conference.

Malignant islet cell tumor with sarcomatous differentiation.

Malignant mesenchymal neoplasms of the pancreas are rare and malignant islet cell tumors with sarcomatous dedifferentiation are rarer still. We present a case of malignant islet cell tumor with sarcomatous differentiation, which to our knowledge is only the second reported case showing such a combination of morphologic features. Clinically, the neoplasm was not hormonally active and immunohistochemical staining was negative for gastrin, glucagon, insulin and somatostatin. The sarcomatous component strongly reacted with an antibody directed against vimentin, and a minority of cells stained strongly with antisera directed against desmin and smooth muscle actin. The spindle cell component was nonreactive with antibodies directed against Factor VIII. The myogenous direction of differentiation in the present tumor is similar to that seen in the prior case report of malignant islet cell tumor with rhabdomyosarcomatous differentiation.

Are myogenin and myoD1 expression specific for rhabdomyosarcoma? A study of 150 cases, with emphasis on spindle cell mimics.

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood, displays a variety of histologic patterns. Immunohistochemistry is used extensively to distinguish RMS from its mimics. Myogenin and MyoD1, myogenic transcriptional regulatory proteins expressed early in skeletal muscle differentiation, are considered sensitive and specific markers for RMS and are more specific than desmin and muscle-specific actin and more sensitive than myoglobin. Previous studies have focused on expression of myogenin and MyoD1 in small round cell tumors. This study assesses myogenin and MyoD1 in rhabdomyosarcoma subtypes and spindle cell tumors considered in the differential diagnosis of RMS. Formalin-fixed, paraffin-embedded archival tissue from 32 RMS, 107 non-RMS, and 11 benign skeletal muscle samples was stained for myogenin and MyoD1 with standard immunohistochemical techniques. Nuclear positivity was scored on a three-tiered scale. All RMSs expressed myogenin. Alveolar RMS (ARMS) showed strong nuclear staining, especially in tumor cells lining fibrous septae and perivascular regions. In cases with a subtle alveolar architecture on routinely stained sections, myogenin highlighted and enhanced visualization of the alveolar morphologic pattern. Embryonal RMSs (ERMSs) were more variable in myogenin staining pattern and intensity. No cases of nodular fasciitis, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, inflammatory myofibroblastic tumor, myofibrosarcoma, leiomyoma, leiomyosarcoma, or alveolar soft part sarcoma stained for myogenin. Focal nuclear reactivity was seen in desmoid (2 of 10), infantile myofibromatosis (2 of 10), synovial sarcoma (1 of 10), and infantile fibrosarcoma (2 of 10). Non-neoplastic skeletal muscle fiber nuclei stained positively for myogenin in both tumor-associated samples (25 of 40) and benign skeletal muscle samples (5 of 11). Although all RMSs were immunoreactive for MyoD1, cytoplasmic and nonspecific background staining and reactivity of nonmyoid tissues hindered its practical utility in paraffin-embedded samples in this study. Although myogenin is a highly sensitive and specific marker for RMS, it is rarely seen in other spindle cell soft tissue tumors. As previously reported, ARMS stained more strongly than ERMS. In contrast to previous studies, rare non-RMS (7 of 107) displayed focal nuclear reactivity, and entrapped atrophic or regenerative skeletal muscle fibers also stained positively. Although these are potential pitfalls in the interpretation of myogenin, careful attention to morphology and other features, to the relative paucity of myogenin-positive nuclei in non-RMS. and to the presence of entrapped muscle fibers should prevent incorrect interpretation. Because the extent of myogenin expression in RMS is much greater than in non-RMS, it is a very useful marker when interpreted in the context of other clinicopathologic data.

Immediate on-site interpretation of fine-needle aspiration smears: a cost and compensation analysis.

BACKGROUND: A significant body of literature exists supporting the cost effectiveness of fine-needle aspiration (FNA) cytology in the work-up of patients with potential neoplastic disease. Several authorities have stated that immediate, on-site smear evaluation by cytopathologists optimizes diagnostic accuracy and minimizes the technique's insufficiency rate. This favorable effect on FNA diagnostic accuracy is most pronounced for deep body sites, where FNA is guided by computed tomography (CT), ultrasound, bronchoscopy, or endoscopy. Little data exist regarding whether compensation from Medicare is adequate to support the pathologist in this endeavor compared with other potentially more remunerative activities, including routine surgical pathology sign-out, nongynecologic cytopathology sign-out, and frozen section consultation. METHODS: The authors studied a series of 142 fine-needle aspirates with immediate, on-site evaluations performed under a variety of clinical settings. These included bronchoscopic, endoscopic, ultrasound-guided, and CT-guided biopsies along with palpation-directed biopsies performed by either cytopathologists or clinicians. For these aspirates, total pathologist attendance time was calculated and correlated with guidance technique, target organ, location where aspirate was performed, and nature of aspirator. Fifty frozen section evaluations were timed similarly. For comparison purposes, cytopathologists' costs were calculated using the 80th percentile pay level of an associate professor with full-time clinical duties. Medicare rate schedules were used to calculate compensation. Including salary and benefits, the pathologist cost was approximately $88.83 per hour. RESULTS: On average, an intraprocedural FNA evaluation for a CT-guided biopsy required 48.7 minutes, an ultrasound-guided biopsy required 44.4 minutes of pathologist time, an endoscopic procedure required 56.2 minutes, a bronchoscopic procedure required 55.3 minutes, a clinic aspirate performed by a pathologist required 42.5 minutes, and a clinic FNA performed by a clinician required 34.7 minutes. The average frozen section required 15.7 minutes of pathologist time for performance and interpretation. With the exception of FNA performed in clinic by the cytopathologist, time costs exceeded compensation by $40-50 per procedure. Clinic aspirates performed by a clinician and immediately evaluated by a pathologist resulted in a deficit of approximately $18 over actual time cost. CONCLUSIONS: From the current data, it appears that intraprocedural consultations by cytopathologists for CT-guided, ultrasound-guided, bronchoscopic, or endoscopic procedures are compensated insufficiently by current Medicare compensation schedules using the CPT code 88172 for on-site evaluation. Only when the cytopathologist personally performs the aspirate and immediately interprets it (CPT codes 88172 and 88170) does the Medicare payment adequately compensate for professional services.

Value of topoisomerase II alpha, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu immunohistochemical expression for the prediction of biologic behavior in adrenocortical neoplasms.

Prediction of biologic behavior in adrenocortical neoplasms is difficult because of the lack of availability of reliable clinical, biochemical, and pathologic prognostic markers. Reliable objective markers predictive of clinical outcome in adrenocortical neoplasms are needed to assign optimal treatment of potentially malignant tumors. In the current article, the authors evaluated a set of molecular markers (topoisomerase II alpha (Topo II alpha), MIB-1, p53, human epithelial cadherin (E-cadherin), retinoblastoma gene protein product, and HER-2/neu) and correlated their expression with histologic diagnosis and clinical outcome. Paraffin-embedded, formalin-fixed tissue blocks from 30 cases of adrenocortical neoplasms (15 benign and 15 malignant) were obtained from the surgical pathology archives at the University of Utah Health Sciences Center (Salt Lake City, UT) and the Medical College of Wisconsin (Milwaukee, WI). Age, gender, recurrence, tumor size and weight, hemorrhage, necrosis, pleomorphism, mitotic count, capsular and lymphovascular invasion, hyaline globules, intranuclear inclusions, and immunohistochemical expression of Topo II alpha, p53, MIB-1, E-cadherin, retinoblastoma gene protein product, and HER-2/neu were studied. Clinical data were obtained from the clinical charts, or communication with the treating physician, or both. Adrenocortical neoplasms with hemorrhage, necrosis, large size (>5 cm), weight more than 100 g, nuclear pleomorphism, lymphovascular invasion, and brisk mitotic rate (more than 5 per 30 high-power fields) were more likely to behave in a malignant fashion (P approximately 0.001-0.009). The difference in proliferation indices in benign and malignant neoplasms was statistically significant (P < 0.001). The difference in p53 staining in benign and malignant neoplasms also was statistically significant (P < 0.001). Higher p53 labeling index (>20%) was present in 73% (11/15) of malignant lesions but was found in only 1 of 15 (6.6%) benign lesions. The difference in retinoblastoma staining between benign and malignant neoplasms was statistically significant (P = 0.004). There was no significant difference in staining pattern of E-cadherin expression between benign and malignant lesions. HER-2/neu overexpression was not observed in any of the benign or malignant adrenocortical neoplasms.

Atypical squamous epithelium in cytologic specimens from the pancreas: cytological differential diagnosis and clinical implications.

Atypical squamous epithelium is an uncommon finding in cytologic specimens obtained from pancreatic lesions. A variety of pathologic conditions can result in the presence of these cells, including primary or metastatic carcinomas, chronic pancreatitis, and squamous metaplasia related to pancreatic or biliary duct stent placement. Primary adenosquamous and squamous-cell carcinomas of the pancreas are rare, representing 3.4% and 1.4 % of pancreatic carcinomas, respectively. Cytologic separation of these malignancies from less ominous metaplasias has immense clinical importance. We reviewed Indiana University Hospital's and Duke University's experiences with atypical squamous epithelium occurring within pancreatic aspirates. Study cases were identified using a computer to search the cytology records of these two institutions. Nine cases with a diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or atypical squamous epithelium were retrieved from the two institutions' Department of Pathology files. One case of pure squamous-cell carcinoma occurred in a patient with a known pulmonary primary; a single case of adenosquamous carcinoma was diagnosed in a patient with a coexistent endometrial primary; a single sample of adenocarcinoma with squamous differentiation was diagnosed in a patient without other known disease; and four primary squamous-cell carcinomas of the pancreas were detected. In addition, a single case of atypical squamous metaplasia associated with a stent was identified, and one case of atypical squamous epithelium associated with chronic pancreatitis was diagnosed. Despite the reactive atypia present in the examples of metaplastic squamous epithelium, separation of these cases from true squamous-cell carcinoma and adenosquamous carcinoma was achievable by cytologic evaluation. No cytologic criteria aided in separating primary pancreatic carcinomas with squamous differentiation from metastatic lesions. In this study, we report our findings in a series of nine cases where cytology disclosed atypical squamous epithelium in the aspirates derived from pancreatic lesions.

A phase II trial testing the thermal dose parameter CEM43 degrees T90 as a predictor of response in soft tissue sarcomas treated with pre-operative thermoradiotherapy.

We prospectively evaluated whether delivering a thermal dose of > 10 cumulative equivalent minutes at 43 degrees C to >90% of the tumour sites monitored (CEM43 degrees T90) would produce a pathologic complete response (pCR) in > 75% of high-grade soft tissue sarcomas treated pre-operatively with thermoradiotherapy. The impact of thermal dose on local failure (LF), distant metastasis (DM), and toxicity was also assessed. Thirty-five patients > or = 18 years old with grade 2 or 3 soft tissue sarcomas accessible for invasive thermometry were enrolled on the protocol. All patients received megavoltage external beam radiotherapy (RT) in daily fractions of 1.8-2.0 Gy, five times a week, to a median total dose of 50 Gy and an initial hyperthermia treatment (HT) of I h duration utilizing the BSD 2000 with Sigma 60 or MAPA applicators at frequencies of 60-140 MHz. Further HT was given for patients with CEM43 degrees T90 > 0.5 after initial HT ('heatable' patients), twice a week to a maximum of 10 HT or CEM43 degrees T90 > 100. Of the 35 patients entered, 30 had heatable tumours, one of which was inevaluable for pCR or LF as the patient died of DM prior to surgery, leaving 29 evaluable patients. Of these 29 patients, 15 (52%) had a pCR (95% CI: 37-73%), significantly less than the projected rate of > or = 75% (p = 0.02). Of the 25 heatable tumours that achieved CEM43 degrees T90 > or = 10, 14 (56%) had a pCR (95% CI: 39-78%) significantly less than the projected rate (p = 0.06). Three of the 29 patients (10%) with heatable tumours had a LF, versus 1/5 unheatable tumours (p = 0.48). Fourteen of the 30 patients (47%) with heatable tumours developed DM, versus 2/5 unheatable tumours (p = 1.00). Ten of the 30 patients (33%) with heatable tumours developed treatment-induced toxicity. Thus, no correlation of thermal dose with histologic response was observed. Prospective control of CEM43 degrees T90 failed to achieve the projected pCR rate following pre-operative thermoradiotherapy for high-grade soft tissue sarcomas, despite excellent local control. Possible explanations for this outcome are discussed.

A comparison of routine and rapid microwave tissue processing in a surgical pathology laboratory. Quality of histologic sections and advantages of microwave processing.

Rapid processing of histopathologic material is becoming increasingly desirable to fulfill the needs of clinicians treating acutely ill patients. Traditional techniques for rapid processing of paraffin-embedded tissues require 4 to 5 hours, delaying treatment for some critically ill patients and requiring additional shifts of technologists in the laboratory. Microwave processing further shortens this time, allowing even more rapid histopathologic diagnosis. Few data exist comparing quality of microwave-processed tissue with that processed by more traditional techniques. We randomly selected 158 paired specimens from 111 patients. One member of the pair was processed routinely overnight, while the other was processed by the rapid microwave technique. The slides then were compared for quality of histologic preparation in a blinded fashion by 2 pathologists. Eight routinely processed specimens were judged as suboptimal, while 6 microwave-processed specimens were judged as suboptimal and 1 was considered unsatisfactory for evaluation. In the remaining cases, the material obtained by the 2 techniques was considered of identical quality. Microwave processing considerably shortens the preparation time for permanent histologic sections without a demonstrable decrease in section quality or "readability."

E-cadherin reactivity of 95 noninvasive ductal and lobular lesions of the breast. Implications for the interpretation of problematic lesions.

Studies suggest that E-cadherin is useful to classify epithelial breast lesions as ductal or lobular, but extensive experience with this antibody is lacking. We studied reactivity of lesions with classic and indeterminate morphologic features. We reviewed 95 lesions and divided them into unanimous and nonunanimous diagnosis groups; the unanimous group served as benchmark lesions to which E-cadherin reactivity could be standardized and compared. All 37 ductal lesions in the unanimous group had strong, diffuse E-cadherin reactivity. Two of 22 classic lobular carcinoma in situ (LCIS) lesions had sparse E-cadherin-reactive lobular cells within a few terminal duct lobular units. Neither displayed transition from nonreactive to reactive cells. Of 36 lesions in the nonunanimous group, 19 had insufficient morphologic features for definitive classification. Only 6 of 19 were E-cadherin reactive, including several minimally proliferative lesions. The other 17 lesions in the nonunanimous group had LCIS and ductal carcinoma in situ (DCIS) features. All had no E-cadherin, or strong membrane reactivity of constituent cells in varying proportions, without a transition between reactive and nonreactive cells. Results suggest that the majority of morphologically nondiagnostic atypical lesions are lobular, including those associated with DCIS. E-cadherin seems to be absent in most lobular lesions.

Significance of lymphoglandular bodies in bone marrow aspiration smears.

The presence of lymphoglandular bodies (LGB) or Söderström bodies is often stated to be a feature of lymphoid processes. In our experience, LGB are typically identified in B-cell processes but not in T-cell lymphomas or myeloid leukemias. We reviewed 136 bone marrow aspirate smears. The number of LGB per five high-power fields was counted, and median counts for B-cell processes, non-B-cell processes, myeloid leukemias, and T-cell malignancies were obtained and compared by the Wilcoxon rank sum test. Bone marrow aspirate smears involved with B-cell malignancies contained a median of 30 (range, 1-250) LGB per five high-power fields. Compared to myeloid leukemias (median, 11; range, 1-253) and T-cell malignancies (median, 7; range, 0-41), the differences were statistically significant (P < 0.001 and P = 0.01, respectively). While lymphoglandular bodies can be seen in a variety of malignant hematopoietic and nonhematopoietic disorders, they are found in significantly greater numbers in B-cell malignancies.

Fine-needle aspiration biopsy of alveolar rhabdomyosarcoma of the parotid: a case report and review of the literature.

The cytologic features of an alveolar rhabdomyosarcoma arising within the parotid gland are described. The occurrence of this neoplasm as a primary malignancy in the parotid gland is very rare, and the tumor is usually not included in the cytologic differential diagnosis of parotid tumors. The diagnosis of the current case was achieved by a combination of fine-needle aspiration biopsy and frozen sections. Realizing the difficulty of recognizing this tumor both histologically and cytologically, we present this case to increase the awareness of this tumor's occurrence within the parotid gland and other salivary glands, and to highlight cytomorphologic features that will aid the pathologist in making the correct diagnosis.

A comparison of touch imprint cytology and Mohs frozen-section histology in the evaluation of Mohs micrographic surgical margins.

BACKGROUND: Touch imprint cytology (TIC) is commonly used in the diagnosis of tumors and has been applied to margin analysis of breast lumpectomy specimens with good success. OBJECTIVE: Our purpose was to determine the diagnostic adequacy of TIC for identifying positive and negative Mohs surgical margins for basal cell carcinoma (BCC) excisions, compared with the "gold" standard, Mohs tangential sectioning. METHODS: Fifty-eight patients undergoing 69 Mohs micrographic surgical procedures for biopsy-proven BCC were included in this study between October 1998 and January 1999. Patients were excluded if the neoplasms were of another histologic type, including BCCs with squamous features. One hundred sixty-six touch imprint slides were prepared from 166 fragments of skin tissue excised during MMS. Touch imprint slides were evaluated blindly and independently by two pathologists, one of whom was also a cytopathologist. The slides were diagnosed as positive for tumor, negative for tumor, or, rarely, atypical but suspect for tumor. Discrepancies between the pathologists' interpretations were re-evaluated with the use of a two-headed microscope and a consensus was reached. After all cytologic interpretation was completed, the results were compared with the histologic diagnosis rendered for each fragment of tissue by the Mohs surgeon. RESULTS: The prevalence of a positive margin by histologic confirmation was 55% overall, 60% for recurrent or sclerosing lesions, and 51% for nonsclerosing or recurrent lesions. The overall accuracy of this technique in identifying true positive and true negative margins was 71%. The sensitivity of TIC for identifying a positive margin was approximately 50% for all BCC types. The specificity was approximately 90% for all BCC types. CONCLUSION: TIC is inadequate for identifying positive margins compared with the "gold" standard, MMS.

Topoisomerase alpha II, retinoblastoma gene product, and p53: potential relationships with aggressive behavior and malignant transformation in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) has a juvenile aggressive form and an adult more indolent form. Most cases of RRP are cytologically benign; however, some undergo malignant transformation. At present, there are no known markers that help identify patients at risk for aggressive disease. We investigated by immunohistochemistry expressions of topoisomerase alpha II, MIB-1, p53, p21, E-cadherin, retinoblastoma (RB) gene protein product, HER-2/neu, and steroid hormone receptors in a case of juvenile respiratory papillomatosis with malignant transformation to determine whether these markers are associated with malignant transformation. Histologic examination of the pulmonary lobectomy specimen revealed well-differentiated squamous carcinoma and invasive papillomatosis. Increased staining was found in areas of invasive papillomatosis for topoisomerase alpha II, p53, and MIB-1, with highest labeling indices in areas of squamous carcinoma. Staining intensity for RB gene protein product showed gradual decline from benign papilloma (3+) and invasive papillomatosis (2+) to squamous carcinoma (0-1+). Expression of p21 was similar in benign papilloma and invasive papillomatosis but showed reduction in squamous carcinoma. Expressions of E-cadherin, HER-2/neu, and steroid hormone receptors did not appear to correlate with biologic behavior. Increased topoisomerase alpha II and p53 expression along with reduced RB gene protein product and p21 expression may serve as markers of transformation to invasive papillomatosis and squamous carcinoma.

Prognostic value of immunohistochemical expression of topoisomerase alpha II, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu in adrenal and extra-adrenal pheochromocytomas.

No reliable pathologic criteria have been identified that predict clinical behavior in adrenal and extra-adrenal pheochromocytomas (PHEOs). Reliable prognostic markers for the prediction of clinical outcome are needed to assign optimal treatment for potentially malignant tumors. In this report, we evaluated several molecular markers (topoisomerase II alpha, E-cadherin, HER-2/neu, and retinoblastoma (RB) gene protein) that have not been previously studied in PHEOs. Paraffin-embedded, formalin-fixed tissue blocks from 50 cases of PHEO (30 benign and 20 malignant, 31 adrenal and 19 extra-adrenal) were obtained from University of Utah Health Sciences Center, Salt Lake City, and the Medical College of Wisconsin, Milwaukee. Gross (tumor size, weight, local extension, cyst formation, hemorrhage, necrosis), microscopic (pleomorphism, hyaline globules, intranuclear inclusion, mitotic count, capsular and vascular invasion, ganglionic/neuronal differentiation), and immunohistochemical features (topoisomerase II alpha, p53, MIB-1, E-cadherin, RB, and HER-2/neu) were studied. With the exception of vascular invasion (P = 0.025), there were no unequivocal gross or microscopic characteristics that distinguished benign from malignant lesions (P approximately = 0.11-0.71). Topoisomerase III and MIB-1 indices in malignant lesions were significantly higher than those observed in benign lesions (P = 0.012 and 0.019). Differences in p53 expression were not statistically significant (P = 0.082). Loss in RB protein product expression was significantly more common in malignant lesions (P = 0.001), E-cadherin loss and HER-2/-neu overexpression were not observed in any of the benign or malignant lesions. We studied the immunohistochemical expression of topoisomerase II alpha, MIB-1, p53, RB gene protein product, E-cadherin, and HER-2/neu in a series of adrenal and extra-adrenal PHEOs. Overexpression of topoisomerase II alpha and MIB-1 and loss of RB protein product were more common in malignant lesions, whereas p53, E-cadherin, and HER-2/neu do not seem to have diagnostic utility in the prediction of biologic behavior in these neoplasms.