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Cytokeratin 7/20 and mucin core protein expression in ulcerative colitis-associated colorectal neoplasms.

Different histogenetic pathways have been suggested between ulcerative colitis (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To clarify the characteristics of UC-associated colorectal carcinogenesis, we examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6 in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7 was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and 89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and 12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC associated neoplasia 67% in AC and 20% in TA. There were obvious differences in the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also higher than sporadic tumors. These results suggest that gastric-type mucins play an important role in the initial step of CC-tumorigenesis, and CK7 and gastric-type mucins may be useful in the differential diagnosis between UC-associated neoplasms and sporadic ones.

Adenocarcinoma↗

Facial nerve function after parotidectomy for neoplasms with deep localization.

PURPOSE: To determine whether the deep location of a parotid gland neoplasm is specific risk factor for facial nerve paralysis after parotidectomy. METHODS: We retrospectively reviewed 88 patients, including 59 with a benign superficial neoplasm of the parotid treated by superficial parotidectomy (group 1); 5 with a benign deep neoplasm treated by total parotidectomy (group 2); 20 with a malignant superficial neoplasm treated by total parotidectomy (group 3); and 4 with a malignant deep neoplasm treated by total parotidectomy (group 4). RESULTS: Temporary facial nerve paralysis developed in 10.3%, 20%, 10%, and 50% of groups, 1, 2, 3, and 4, respectively. Permanent facial nerve paralysis developed in 0%, 0%, 10% and 50% of groups 1, 2, 3, and 4, respectively. CONCLUSION: The risk factor associated with nerve damage resulting from surgery for parotid neoplasms were malignancy and deep localization. However, the deep location of a benign tumor was not a major risk factor for permanent paralysis.

Adult↗

Cystic pancreatic neoplasms: enucleate or resect?

Asymptomatic cystic pancreatic neoplasms are being detected by abdominal imaging with increasing frequency. Enucleation of small cystic neoplasms can be performed without recurrence but has been associated with a higher incidence of pancreatic fistula. Thus the procedure has been modified to include intraoperative ultrasound imaging and closure of the pancreatic defect. This analysis was performed to determine whether these modifications have improved operative outcome. Thirty patients with mucinous cystic neoplasms (n=16), serous cystadenomas (n=10), and cystic islet cell tumors (n=4) were studied. Enucleation was performed in 11 patients (7 with mucinous cystic neoplasms, 2 with serous cystadenomas and 2 with islet cell tumors), whereas 19 underwent resection of cystic tumors (pancreatoduodenectomy in 8 and distal pancreatectomy in 11). The mean groups did not differ with regard to age (57 years), gender (73% female), presentation (63% incidental), or site (43% head, neck, or uncinate). Patients undergoing enucleation had smaller tumors (2.2 vs. 4.7 cm, P<0.01) that were less likely to be in the tail (9% vs. 42%). Operative time was significantly shorter in the enucleation group (199 vs. 298 minutes, P<0.01). Blood loss also was significantly reduced in the enucleation group (114 vs. 450 ml, P<0.001). Pancreatic fistula rates (27% vs. 26%) and length of hospital stay (12.6 vs. 15.7 days) were similar in the two groups. Enucleation of benign cystic pancreatic neoplasms reduces operative time and blood loss without increasing postoperative complications or length of stay. Therefore enucleation should be the standard operation for small benign cystic neoplasms in the uncinate, head, neck, and body of the pancreas.

Adenoma, Islet Cell↗

A comparative immunohistochemical study of uterine smooth muscle neoplasms with emphasis on the epithelioid variant.

We evaluated the immunophenotypes of 22 spindled and 36 epithelioid uterine smooth muscle neoplasms (SMNs) and 16 extrauterine nongastrointestinal spindled smooth-muscle neoplasms for various markers. The epithelioid neoplasms were subdivided into two histological groups designated true and intermediate, the former showing typical epithelioid features and the latter showing epithelioid features that could be explained by cross-sectioning of blunt spindled cells. Desmin, muscle-specific actin, and smooth muscle actin were equally sensitive in detecting muscle differentiation in all these neoplasms. The true epithelioid variants were more frequently keratin positive but less frequently positive for vimentin, CD34 or the muscle markers, compared with their spindled counterparts. The intermediate epithelioid variants more closely resembled the spindled neoplasms in their immunostaining for muscle markers, vimentin, and CD34 but like the true epithelioid variants were relatively frequently positive for keratin. CD34 was positive in 36% of the spindled and 6% of the true epithelioid uterine SMNs, in most cases faintly. Antikeratin AE1 was positive more frequently than CAM5.2, with 18% of the spindled and 35% of the true epithelioid neoplasms being AE1 positive. The immunophenotype of uterine SMNs, including the epithelioid variant, permits their distinction from carcinomas based on their frequent reactivity for muscle markers in spite of their high rate of keratin positivity. They show sufficient overlap in immunoreactivity with endometrial stromal sarcomas to preclude definitive differentiation from them on immunohistochemical features alone.

Antigens, CD↗

Magnetization transfer contrast imaging of hepatic neoplasms.

A method of performing magnetization transfer contrast (MTC) using a pulse sequence based on a series of on-resonance binomial pulses preceding a conventional spin-echo sequence has been recently described. We investigated this technique in the evaluation of circumscribed hepatic neoplasms on a 0.5 T imager. Conventional spin-echo imaging was performed in 18 patients with hepatic neoplasms, 15 with primary or metastatic hepatic neoplasms, and 3 with cavernous hemangiomas. The T1-weighted sequence was repeated following MTC saturation in 7 patients and the proton density sequence was repeated following MTC saturation in 13 patients (both were used in two patients). The mean lesion-to-liver contrast for neoplasms worsened with T1-MTC (0.87 vs. 1.04), but improved slightly with proton density-MTC (1.10 vs. 1.22) when compared to the corresponding non-MTC spin-echo images. However, these differences were not statistically significant (p = .19 and p = .16, respectively). The limited data on cavernous hemangiomas does not suggest these have consistently different MTC imaging characteristics from other hepatic neoplasms. In conclusion, MTC imaging using a binomial saturation pulse did not offer significant improvement in contrast between hepatic neoplasms and normal liver. Refinements of the binomial pulse sequence will be necessary if a consistent improvement in lesion sensitivity is to be achieved. Evaluation of its role in increasing diagnostic specificity will require further investigation.

Adenoma↗

Diagnostic and prognostic value of angiogenesis-modulating genes in malignant thyroid neoplasms.

BACKGROUND: Angiogenesis is an essential biologic event in the pathogenesis of human malignancies. We postulated that expression analysis of genes that modulate angiogenesis would identify differentially expressed genes that would help to distinguish benign from malignant thyroid neoplasms and serve as markers of aggressive differentiated thyroid cancer. METHODS: A complementary DNA (cDNA) array with 96 genes that modulate angiogenesis was used to identify differentially expressed genes (2-fold higher or lower) in malignant versus benign thyroid neoplasms. Real-time quantitative polymerase chain reaction was used to confirm cDNA array expression data in 123 patients (4 normal thyroid, 26 hyperplastic nodules, 27 follicular adenomas, 23 follicular cancers, 18 follicular variant of papillary cancers, 25 papillary cancers). RESULTS: Twenty-two genes were upregulated in malignant thyroid neoplasms by cDNA array analysis, but only 13 genes had higher messenger RNA (mRNA) expression levels in malignant than in benign thyroid neoplasms by real-time quantitative polymerase chain reaction (P < or = .04). Of the 13 differentially expressed genes, the combined use of angiopoietin 2 (ANGPT2) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression levels was best for distinguishing malignant from benign thyroid neoplasms, with a sensitivity of 90%, specificity of 85%, positive predictive value of 75%, and negative predictive value of 94%. Epidermal growth factor receptor and ephrin B2 mRNA expression was elevated in higher TNM stage neoplasms and in patients with high-risk AMES (Age, distant Metastasis, Extrathyroidal invasion, and tumor Size) differentiated thyroid cancers (P < or = .005). CONCLUSIONS: Angiopoietin 2 and tissue inhibitor of metalloproteinase 1 are diagnostic markers of malignant thyroid nodules and could improve the diagnostic accuracy of FNA biopsy. Epidermal growth factor receptor and ephrin B2 are markers of aggressive differentiated thyroid cancer.

Adenocarcinoma, Follicular↗

Ovarian neoplasms and the risk of adnexal torsion.

Previous reports examining adnexal torsion suggested that benign ovarian neoplasms are more likely to undergo torsion than malignant ovarian neoplasms. To our knowledge, this clinical observation has not been quantified. To examine this hypothesis, we reviewed our experience with ovarian neoplasms found at the time of surgery over a 10-year period. Benign ovarian neoplasms had a 12.9-fold increased risk of undergoing adnexal torsion when compared with malignant ovarian neoplasms (95% confidence interval, 10.2 to 15.9). The histologic type of ovarian neoplasm does not appear to affect the rate of adnexal torsion. Adnexal torsion rarely involves cancer.

Adnexal Diseases↗

An aggressive resectional approach to cystic neoplasms of the pancreas.

BACKGROUND: Prognosis is good after curative resection for serous and mucinous cystic neoplasms of the pancreas. There has been a recent trend to resect all cystic neoplasms, without attempts to preoperatively determine the exact histologic subtype. Our purpose is to report on the results of such an aggressive surgical approach to all cystic neoplasms of the pancreas. METHODS: This is a retrospective cohort analysis of 25 patients with cystic neoplasms of the pancreas treated between July 1991 and July 1998. Data include patient demographics, presenting symptom, operative procedure, pathologic diagnosis, periop morbidity and mortality, survival, and symptomatic follow-up data. RESULTS: Twenty-one patients were women, with a mean age of 60 for the entire cohort. Mean follow-up was 24 months (range 6 months to 4.3 years) with complete follow-up possible in 92%. Twenty-three patients had curative resections and 2 had palliative resections. One patient with an uncinate mass had a partial pancreatectomy; 4 patients underwent distal pancreatectomy and 9 had distal pancreatectomy with splenectomy; 11 patients required a pancreatoduodenectomy, and of these, 4 had tumors involving the portal vein, necessitating a portal vein resection. Pathologic analysis revealed 12 serous cystadenomas, 4 mucinous cystadenomas, 3 mucinous cystadenocarcinomas, 5 intraductal papillary cystic neoplasms, and 1 serous cystadenocarcinoma. The overall perioperative complication rate was 40% with 5 major and 5 minor complications. In the 11 pancreatoduodenectomy patients alone, there were 1 major and 4 minor complications. There were no pancreatic fistulas or portal vein thromboses and no operative mortalities. Two patients, both with mucinous cystadenocarcinomas, died of their disease at 6 and 16 months postoperatively. All 11 pancreatoduodenectomy patients have only mild pancreatic insufficiency relieved by daily enzyme replacement. CONCLUSIONS: The good outcomes in this study support an aggressive surgical approach to all patients diagnosed with a cystic neoplasm of the pancreas, if medically fit to tolerate surgery. This approach is justified for the following reasons: (1) preoperative differentiation of a benign versus malignant tumor is unreliable and routine testing for this purpose is of questionable utility; (2) potential adverse consequences of nonresectional therapy are significant; (3) perioperative morbidity and mortality of pancreatic surgery is low; and (4) prognosis with curative resection is good.

Adult↗

The completeness and accuracy of health authority and cancer registry records according to a study of ovarian neoplasms.

The completeness and accuracy of Hospital Activity Analysis (HAA) and Regional Cancer Registry (RCR) records were investigated in a series of 868 histologically reviewed cases in which primary ovarian neoplasms had been diagnosed according to one or more of seven data sources including HAA and RCR. All the women concerned were residents of Manchester and Salford who had presented in 1979-83 aged 15 years or more. The histological review confirmed the diagnosis of ovarian neoplasia in 829 of these women and excluded it in 39. Among the 829 confirmed cases, 333 were malignant or of borderline malignancy and therefore eligible for registration with the RCR, and 496 were benign. Only 611 (74%) of the 829 cases were listed as ovarian neoplasms or cysts in HAA records of hospital admissions from the study area during the study period, and the HAA diagnosis was incorrect in 40% of the 611 listed cases. Among the 333 borderline or malignant cases, only 241 (72%) appeared among the RCR's registrations of ovarian neoplasms for the study period and area. The RCR record of histological diagnosis was inaccurate in over 20% of these 241 registered cases, although most of the inaccuracies did not affect whether the neoplasm was classified as borderline or malignant. Five per cent of the cases listed as ovarian neoplasms in the HAA file and 15% of those listed as registrable ovarian neoplasms by the RCR should not have been so listed. The findings highlight the limitations of these routine health information systems, both as sources of cases for research and as National Health Service management tools.

Adolescent↗

Chromosomal and DNA ploidy characterization of salivary gland neoplasms by combined FISH and flow cytometry.

Concurrent DNA ploidy by flow cytometry and interphase FISH analysis of chromosomes 6 through 12, 17, 18, X, and Y were prospectively performed on 22 salivary gland neoplasms (four benign and 18 malignant) to investigate the diagnostic and biological implications of their alterations in these neoplasms. Our results show that benign neoplasms lack DNA aneuploidy and numerical chromosomal abnormalities. Low-grade malignant neoplasms, except for two lesions, manifested small chromosomal gains and losses and were generally DNA diploid or near-diploid aneuploid, whereas all high-grade tumors showed marked polysomy and were DNA aneuploid. Marked intratumoral and intertumoral chromosomal heterogeneity also were noted in and between individual tumors. Although polysomy was the main finding in DNA aneuploid lesions, monosomy was more noted in DNA diploid neoplasms and was restricted to chromosomes 8, 11, and 17. Significant correlation between the DNA index, chromosomal aneusomy, histological grade, and tumor stage was noted. Our study indicates that (1) benign salivary gland neoplasms lack gross DNA content and numerical chromosomal abnormalities, (2) clonal chromosomal alterations are manifested in most DNA diploid and all DNA aneuploid malignant tumors, (3) chromosomal gain is the most common alteration; chromosomal loss is less frequent and restricted to certain chromosomes, and (4) DNA aneuploidy and chromosomal aneusomy characterize tumors with aggressive features.

Adult↗

Histogenesis of salivary gland neoplasms: a postulate with prognostic implications.

In a continually renewing cell population, stem cells can be regarded as a reservoir of cells with a high capacity for self renewal that give rise to all differentiated progeny. They are the primary source for the generation and maintenance of cellular diversity and tissue homeostasis. In general, neoplasms manifest differentiation pathways similar to those found in the development and renewal of the normal tissues from which they arise. This feature serves as a basis for classification schemes of neoplasms and, as in the normal tissues, there is usually an inverse correlation between proliferative capacity and differentiation within the neoplasms. In our postulate of the histogenesis of salivary gland neoplasia, we evoke the stem cell model to account for the considerable phenotypic heterogeneity seen with these neoplasms. We further consider the neoplasms and, in particular, their myoepithelial constituencies to be manifestations of escape from normal regulatory mechanisms that determine differentiation pathways which a stem cell and its progeny can take. Clinical and basic scientific evidence are presented to support the postulate and also to point to the mitigating role that myoepithelial differentiation has in the biological course of salivary gland neoplasms.

Cell Differentiation↗

Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas.

DUSP6/MKP-3 is identified as a candidate tumor suppressor gene for pancreatic cancer. The aim of this study was to elucidate the roles of DUSP6 in the pancreatic carcinogenesis through the pancreatic intraepithelial neoplasia and/or intraductal papillary-mucinous neoplasms, both of which are considered to be precursor lesions of invasive carcinoma of the pancreas, by comparing with involvements of other major tumor suppressive pathways. Expressions of DUSP6, CDKN2A, TP53, and SMAD4 were investigated by immunohistochemistry in a total of 206 lesions of dysplastic ductal precursors and carcinomas retrieved from 52 pancreata with invasive ductal carcinomas and 51 of those with intraductal papillary-mucinous neoplasms. The intensity of staining was evaluated in lesions at different atypical grades and statistically compared among them. Mutations of KRAS2 were analyzed by methods of the allele-specific oligonucleotide hybridization and nucleotide sequencing. In pancreata with invasive ductal carcinomas, expressions of DUSP6 were abrogated exclusively in the invasive carcinoma cells in contrast to its fairly preserved expressions in pancreatic intraepithelial neoplasia. In pancreata with intraductal papillary-mucinous neoplasms, abrogated expressions of DUSP6 were observed in a relatively small fraction of intraductal adenoma/borderlines and intraductal carcinomas. Most of the intraductal adenoma/borderline lesions with abrogation of DUSP6 harbored mutations of KRAS2. None of the molecules was associated with each other in any grade of lesions. Morphological variations of papillae of the intraductal papillary-mucinous neoplasms were evaluated and analyzed for their associations with abrogations of the molecules, which resulted in finding of no significant associations. Our results suggest that the abrogation of DUSP6 is associated exclusively with progression from pancreatic intraepithelial neoplasia to the invasive ductal carcinoma while it is potentially associated with initiation of intraductal papillary-mucinous neoplasms with mutated KRAS2, which is independent of other major tumor suppressive pathways in both types of neoplasms.

Adenocarcinoma, Mucinous↗

Solid pseudopapillary neoplasms of the pancreas are associated with FLI-1 expression, but not with EWS/FLI-1 translocation.

Solid pseudopapillary neoplasms of the pancreas are rare pancreatic tumors with mostly benign behavior, affecting almost exclusively women. Their histogenetic origin is still unsolved, but a recently reported EWS/FLI-1 translocation t(11;22)(q24;q21) and the consistent expression of CD56 and the progesterone receptor, both genes located on the long arm of chromosome 11, point to chromosome 11q as a potential locus of gene aberration in solid pseudopapillary neoplasms. To further elucidate this issue, we studied 30 cases of solid pseudopapillary neoplasms by comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH) and immunohistochemistry. Immunohistochemically, 38% showed nuclear expression of FLI-1 and all cases revealed positivity for CD56 and the progesterone receptor, whereas no solid pseudopapillary neoplasm expressed CD34. No translocation of the EWS gene was found by FISH and no gross chromosomal gain or loss was detected by CGH. It is concluded that FLI-1 expression in solid pseudopapillary neoplasms is not associated with an EWS/FLI-1 translocation. In addition, there are no chromosomal gains or losses, especially on chromosome 11, where the FLI-1 gene is located adjacent to the gene for CD56 (NCAM). These data add another feature to the complex phenotypic appearance of solid pseudopapillary neoplasms.

Adolescent↗

The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--Airlie House, Virginia, November, 1997.

INTRODUCTION: Since 1995, the European Association of Pathologists and the Society for Hematopathology have been developing a new World Health Organization (WHO) classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. MATERIALS AND METHODS: The WHO project involves ten committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC) of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November 1997 to discuss clinical issues related to the classification. RESULTS: WHO has adopted the 'Revised European-American Classification of Lymphoid Neoplasms' (REAL), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. The WHO classification has applied the principles of the REAL classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). CONCLUSION: The experience of developing the WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.

Hematologic Neoplasms↗

Flat colorectal neoplasms and the impact of the revised Vienna Classification on their reporting: a case-control study in UK and Japanese patients.

OBJECTIVE: The prevalence and interpretation of flat colorectal neoplasms in the East or West remain highly variable. Several factors may contribute to this variability including differences in reporting techniques between Japanese and Western histopathologists when lesions are classified. The aims of this study were (i) to determine the frequency and characteristics of flat colorectal neoplasms in British and Japanese patients, (ii) to examine whether histopathological discrepancies exist between Western and Japanese-trained pathologists applying conventional classification methods and (iii) to determine the impact of the revised Vienna Classification on any differences observed. MATERIAL AND METHODS: One hundred and forty-four patients in the United Kingdom with neoplastic lesions prospectively identified by a colonoscopist, fully-trained in Japan, were age and gender-matched with 144 Japanese patients with neoplastic lesions detected by the same colonoscopist. Two British and two Japanese pathologists were independently asked to assess all neoplasms using both conventional and revised Vienna Classification methods. RESULTS: No significant difference in the frequency of flat neoplasms was found between British and Japanese patients; however, flat neoplasia from Japanese patients tended to contain more advanced pathologies. Discrepancies in histological diagnoses were observed between pathologists but which were reduced with the revised Vienna Classification. Japanese pathologists tended to diagnose higher grades of dysplasia for the same lesion compared to their British counterparts. CONCLUSIONS: The frequency of flat neoplasms in British and Japanese patients is similar. However, Japanese lesions, especially flat (IIb) and slightly depressed (IIc) neoplasms tend to be more biologically aggressive. The revised Vienna Classification achieves greater consensus.

Asian People↗

Hurthle cell neoplasms of the thyroid.

OBJECTIVES/HYPOTHESIS: Hurthle cell tumors are a variant of follicular cell neoplasms. The purpose of the study was to determine the reliability of intraoperative frozen-section analysis for diagnosing Hurthle cell carcinoma and Hurthle cell neoplasm and to evaluate age, gender, and tumor size differences in the incidence of Hurthle cell carcinoma. STUDY DESIGN: Retrospective chart review. METHODS: The records of all patients undergoing thyroid surgery at Long Island Jewish Medical Center (Long Island Campus of the Albert Einstein College of Medicine, New Hyde Park, NY) from 1990 to 2000 were reviewed. Patients were identified whose final pathological finding was Hurthle cell neoplasm or Hurthle cell carcinoma. Age at diagnosis, gender, tumor size, and correlation between frozen-section analysis and final pathological finding was determined. RESULTS: One hundred sixteen patients had Hurthle cell tumors on final pathological finding (49 had Hurthle cell carcinoma and 67 had Hurthle cell neoplasm). Eleven of these patients had incidental papillary carcinoma. There were 24 men and 92 women. Sixty-seven percent of the men (16 of 24) and 36% of the women (33 of 92) had Hurthle cell carcinoma on final pathological finding. The mean ages for Hurthle cell neoplasm and Hurthle cell carcinoma groups were 53 (median age, 50 y) and 58 years (median age, 61 y), respectively. One hundred eleven patients had intraoperative frozen-section analysis. Of the 49 patients with Hurthle cell carcinoma, 9 (19%) were diagnosed by frozen-section analysis, 36 (75%) had indeterminate frozen-section analysis, 3 (6%) were discovered to have papillary carcinoma on frozen-section analysis, and 1 did not have a frozen-section analysis. Multivariate analysis indicated that size correlated with malignancy and that gender did not (P =.0015). CONCLUSIONS: In the study population, only 19% of patients were discovered to have Hurthle cell carcinoma on frozen-section analysis. Sixty-seven percent of men with Hurthle cell neoplasm had malignancies, compared with 36% of women, and this difference was statistically significant.

Adenocarcinoma↗

Calretinin and inhibin are useful in separating adrenocortical neoplasms from pheochromocytomas.

Most adrenocortical neoplasms and pheochromocytomas can be diagnosed by a combination of clinical findings and morphologic features. Occasionally, however, this histologic differential diagnosis requires ancillary tests, such as immunohistochemistry. Both tumors are generally negative for epithelial markers but express synaptophysin. Inhibin and chromogranin are used for the diagnosis of adrenocortical neoplasms and pheochromocytomas, respectively. Both antigens, however, are expressed focally and may be completely negative, particularly in small biopsies. The authors investigated the potential value of adding calretinin to inhibin in the differential diagnosis of these tumors. Fifty-five primary adrenal neoplasms including 33 adrenocortical tumors (21 adenomas and 12 carcinomas), 22 pheochromocytomas, and 7 healthy adrenal glands were examined immunohistochemically for the expression of calretinin and inhibin. Inhibin was demonstrated in 24 (73%) adrenocortical neoplasms. When calretinin was added, the number of tumors staining positively for the two markers alone or in combination increased to 31 (94%). Both antigens showed a focal pattern of distribution in many cases. None of the pheochromocytomas reacted for any of these two markers. Healthy adrenal gland showed a distinct positive and negative pattern of immunoreactivity for both antigens in cortex and medulla, respectively. There were no differences between staining patterns of calretinin and inhibin in healthy adrenal cortex, adrenocortical adenomas, and adrenocortical carcinomas. The authors conclude that the addition of calretinin to inhibin increases the sensitivity of the diagnosis of adrenocortical neoplasms. When used together, they are highly specific and sensitive for the differential diagnosis of these tumors from pheochromocytomas. These markers, however, do not distinguish between benign and malignant adrenocortical neoplasms.

Adrenal Cortex Neoplasms↗

Immunohistochemical analysis of metastatic neoplasms of the central nervous system.

Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of "metastatic neoplasm." In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed.

Algorithms↗