NEWSPath

ANATOMIC PATHOLOGY

Gestational Trophoblastic Diseases: Recent Advances in Histopathologic Diagnosis and Related Genetic Aspects

Hui, Pei , Martel, Maritza ,Parkash, Vinita

Gestational trophoblastic disease refers to a spectrum of proliferative disorders of the placental trophoblast, with a wide range of histologic appearances and clinical behaviors. This review discusses the more recent developments in the diagnosis of these entities. Changes in criteria for the histologic diagnosis of these lesions due to earlier clinical diagnosis are reviewed, and the ability to make more accurate diagnoses due to the introduction of newer antibodies such as p57 is highlighted. A discussion of epithelioid trophoblastic tumor, a newly introduced tumor subtype, with its differential diagnosis from placental-site trophoblastic tumor and squamous cell carcinoma is also presented. Last, a brief discussion on the role of genetic studies and the future direction of research in elucidating the nature of this intriguing group of lesions is presented.

Advances in Anatomic Pathology. 12(3):116-125, May 2005.

Seminoma: A Review With Emphasis on Morphologic Patterns and Differential Diagnosis

Henley, John D. , Ulbright, Thomas M.

Seminoma can manifest a variety of different growth patterns. A solid or nested pattern is the most common and readily recognized. Other patterns include trabecular/cordlike, cribriform/microcystic, tubular and intertubular, several of which may lead to diagnostic confusion with a variety of other tumors. A trabecular or cordlike pattern is common at the periphery of solid/nested areas and is usually not a diagnostic issue. A microcystic/cribriform arrangement, often but not always secondary to intercellular edema, is less common and may be mistaken for yolk sac tumor. The absence or paucity of lymphocytic inflammation in many cases further complicates recognition. A conspicuous pattern of solid or hollow tubules in seminoma may resemble Sertoli cell tumor or an epithelial neoplasm. Finally, an intertubular pattern of growth, common at the periphery of solid/nested seminoma, rarely occurs in a pure form. Purely intertubular tumors have uncommon clinicopathologic features, including absence of a testicular mass, both clinically and on gross examination, and microscopically obscure tumors. The latter occur within a background of tubular atrophy and sclerosis. In all morphologic patterns of seminoma, the tumor cells retain a characteristic appearance. They are large, 15 to 25 [mu]m, rounded, or polyhedral. Cell borders are typically crisp and distinct. Cytoplasm is usually clear or finely granular, and cytoplasmic glycogen is demonstrable on periodic acid-Schiff stain. Occasionally, cells may acquire a plasmacytoid morphology, with densely staining, amphophilic cytoplasm, and a degree of nuclear eccentricity, which complicates the distinction from lymphoma and plasmacytoma. Some cases may show a focal signet ring cell appearance. T cells dominate the lymphoid infiltrates that occur to some extent in virtually all seminomas. Granulomatous inflammation, occurring in up to 50% of cases, varies from ill-defined clusters of epithelioid histiocytes to well-formed granulomas with Langhans-like giant cells. In a fifth of cases, granulomatous inflammation is intense, with potential effacement of virtually all of the neoplastic cells, and such cases must be distinguished from granulomatous orchitis. Up to 20% of usual seminomas contain true syncytiotrophoblast giant cells, which stain positively for human chorionic gonadotropin. Their presence, like the degree of mitotic activity in seminoma, has no established bearing on prognosis. When trophoblast cells are prominent and associated with "blood lakes," misinterpretation as choriocarcinoma may occur. When the diagnosis is in doubt, immunohistochemistry is useful in recognizing all patterns of seminoma and aiding discrimination from other diagnostic considerations. Seminomas stain positively for placental alkaline phosphatase, Oct 3/4, and c-Kit (CD117) and are generally negative for cytokeratins; a panel of immunostains that contains these markers usually suffices to confirm or refute a diagnosis of seminoma.

Pathology Case Reviews. 10(4):167-175, July/August 2005.

Ectopic Decidua of Pelvic Lymph Nodes: A Potential Diagnostic Pitfall

Debbie C. Wu, Sharon Hirschowitz, Sathima Natarajan

Ectopic decidua is one of several benign lymph node inclusions that have been increasingly documented in the literature, most often in postmortem examinations of pregnant woman and recently in pregnant women with cervical squamous cell carcinoma. Although lacking clinical significance of its own, the major diagnostic implication would be misdiagnosis as metastatic carcinoma in the lymph node. Intraoperative frozen sections are often performed prior to radical hysterectomy, leading to a potential alteration of therapy if metastatic carcinoma is identified in the lymph nodes. Authors report such a case of a pregnant woman with cervical squamous cell carcinoma requiring lymphadenectomy and hysterectomy, in which the intraoperative frozen section of a pelvic lymph node with ectopic decidual change was mistakenly identified as metastatic carcinoma. Its histologic resemblance to carcinoma and location within subcapsular sinuses, compounded with the fact that ectopic lymph node decidua is not commonly seen in routine practice, can lead to this diagnostic pitfall. Authors review the literature regarding ectopic decidua, its presence in lymph nodes, and its pathogenesis, as well as review the literature on benign lymph node inclusions.

Although ectopic decidua has been sporadically reported in the literature, pathologists have few opportunities to examine lymph nodes in pregnant or postnatal women, therefore raising the possibility that it may be overlooked or misidentified. In addition to ectopic decidua, there are a number of other types of benign lymph node inclusions, which although usually incidental, may pose diagnostic dilemmas.

This diagnostic pitfall may become especially relevant during frozen section examination. Therapy for cervical squamous carcinoma not uncommonly includes intraoperative frozen section examination of pelvic and paraaortic lymph nodes prior to radical hysterectomy, with the presence of metastases as a potential reason for aborting the procedure and thus altering the course of therapy. Therefore, recognition of the presence of benign lymph node inclusions, most notably ectopic decidua, should be raised.

Archives of Pathology and Laboratory Medicine: Vol. 129, No. 5, pp. e117e120

Localized Malignant Mesothelioma

Allen TC, Cagle PT, Churg AM et al

Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior.Authors report 23 new cases. The mean age at presentation was 63 years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of the tumor, 10 of 21 patients with follow-up data were alive without evidence of disease from 18 months to 11 years after diagnosis. Patients who died had developed local recurrences and metastases, but none had diffuse pleural spread. Localized malignant mesotheliomas should be separated from diffuse malignant mesotheliomas because of their localized presentation, quite different biologic behavior, and far better prognosis.

Am J Surg Pathol. 2005 Jul;29(7):866-873.

Inflammatory myofibroblastic tumor of the breast

Elham Khanafshar, Julia Phillipson, et al

Three patients developed firm, mobile, nontender masses in their breasts. Two were discovered by the patients and one after mammography. Macroscopically, the nodules were firm, circumscribed, yellow on cut sections, and composed of interlacing cytologically bland spindle cells admixed with chronic inflammatory cells, the latter predominantly of lymphocytes and plasma cells. Immunohistochemistry yielded strong smooth-muscle actin reactivity within the spindle cells; 2 lesions were negative for pankeratin, 1 was focally and weakly positive. No lesions were positive for anaplastic lymphoma kinase-1, desmin, S-100, CD34, CD21, or CD35. In each case, a diagnosis of inflammatory myofibroblastic tumor was made (aka, inflammatory pseudotumor). After conservative excision with apparently negative margins, there have been no recurrences, except in one patient who developed a recurrence after 3 months. The latter recurrence was managed successfully with a second excision. Authors report these patients to emphasize the diagnostic features of inflammatory myofibroblastic tumor of the breast and discuss how they can be distinguished from other spindle-cell breast lesions with which they can be confused, especially spindle-cell carcinoma.

Annals of Diagnostic Pathology, June 2005 Volume 9 Number 3

Immunohistochemical detection of cdc2 is useful in predicting survival in patients with mantle cell lymphoma

Hui D, Reiman T, Hanson J et al

Recent cDNA microarray studies have reported the prognostic value of several genes in mantle cell lymphoma patients. Authors aimed to validate the prognostic significance of three of these genes: alpha-tubulin, cdc2, and CENP-F. The protein expression of alpha-tubulin, cdc2, and CENP-F was assessed using immunohistochemistry. Their immunoreactivity in 48 formalin-fixed/paraffin-embedded mantle cell lymphoma tumors was determined by estimating the percentage of positive cells. These results were correlated with the expression of proliferation marker Ki67 and survival. Of these 48 mantle cell lymphoma patients, 41 were men and seven were women. The median age at time of diagnosis was 64.5 years, and the overall median survival was 40 months. In benign lymph nodes, the expression of cdc2 and alpha-tubulin was restricted to the germinal centers; mantle zones were negative. Expression of CENP-F was more uniformly distributed. In mantle cell lymphoma, Ki67 significantly correlated with all three markers (P<0.05, Spearman), but only Ki67 (>50%) and cdc2 (>25%) significantly correlated with shorter survival (P<0.0006, Spearman). Of several clinical parameters examined, international prognostic index of >/=2 correlated with worse clinical outcome, and high clinical stage (ie 4 vs </=3) showed a trend for shorter survival. The prognostic significance of cdc2 and Ki67 was independent of international prognostic index and clinical stage. We have validated the prognostic value of cdc2, and confirmed that of Ki67, in a cohort of mantle cell lymphoma patients. Immunohistochemical detection of cdc2 and Ki67 may be a useful and simple method in evaluating the prognosis of mantle cell lymphoma patients.

Mod Pathol. Jun 3, 2005

Basal cell hyperplasia: An unusual diagnostic dilemma on prostate needle biopsies

Hosler GA, Epstein JI.

Basal cell hyperplasia (BCH) is a well-recognized entity on transurethral resection specimens, but it is an uncommon finding on prostatic needle biopsies, and the diagnostic difficulties with it have not been fully defined on this material. A 13-year (1991-2003) retrospective review of the consult files of one of the authors was performed. In all cases, the focus of BCH was referred for consultation to rule out adenocarcinoma. Thirty-three cases of prominent BCH were identified. The dominant pattern of BCH consisted of either glands (26/33) or solid nests (7/33). Other minor patterns included cribriform (5), pseudocribriform (4), cords (1), and adenoid basal (1). Twelve of 33 cases showed an infiltrative pattern. Other features of BCH included prominent nucleoli (14/33), abnormal secretions (17/33 with dense pink and/or blue mucin), mitoses (6/33), altered stroma with increased cellularity (6/33), calcifications (6/33), intraluminal crystalloids (3/33) and perineural invasion (1/33). By immunohistochemistry, 7 (100%) out of 7 were positive for p63 and 14 (88%) of 16 were positive for high molecular weight cytokeratin. No cases (0/6) were positive for alpha-methylacyl-coenzyme A racemase. Basal cell hyperplasia, as a mimicker of cancer, is an uncommon entity encountered on prostatic needle biopsies. Helpful features for its diagnosis include solid nests, pseudocribriform glands, multilayering of cells, calcifications, and cellular stroma. Immunohistochemistry can be useful for documenting the basal cell layer and demonstrating negative racemase staining.

Hum Pathol. 36(5):480-5-2005

Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literature

M Varma & B Jasani

Immunohistochemistry is widely used to distinguish prostate cancer from benign mimics and to establish the prostatic origin of poorly differentiated carcinoma. Authors critically reviewed the recent advances in prostate cancer immunohistochemistry, including the introduction of newer basal cell markers such as p63 and the discovery of the overexpression of -methylacyl coenzyme A racemase (AMACR) in prostate cancer. The description of newer urothelial markers to aid the distinction of prostate cancer from urothelial carcinoma is also presented together with refinements in the quality control of PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical marker for prostate cancer, it has significant limitations. These limitations are discussed and the need for interpreting AMACR immunoreactivity in the appropriate morphological context and in conjunction with basal call markers is emphasized. Authors also describe the utility of an immunohistochemical panel composed of PSA, PSAP and high molecular weight cytokeratin for distinguishing poorly differentiated prostate cancer from high-grade urothelial carcinoma. A morphological differential diagnosis based selection of immunohistochemical markers is highlighted as a novel approach in the diagnosis of prostate cancer in routine surgical pathology practice.

Histopathology,Vol. 47 Issue 1 Page 1 - July 2005

Molecular pathogenesis of cervical cancer

Article in German

Trunk MJ, Wentzensen N, von Knebel Doeberitz M.

Specific types of the human papillomaviruses (high risk human papillomaviruses) play an essential role in the pathogenesis of cervical cancer. Although infections by these viruses are very common in the general population, only few result in clinically relevant lesions. Continuous and deregulated expression of two viral oncoproteins E6 and E7 in basal or parabasal cells are required to induce and maintain neoplastic growth. In the course of an acute HPV-infection these genes are exclusively expressed in cell cycle arrested, terminally differentiated cells in the intermediate or superficial layers of the epithelium. Accidental activation of these genes in proliferating cells in the basal or parabasal cell layers results in interference with the cell cycle regulation, disturbances of the mitotic spindle apparatus and centrosome functions. This results in numerical and structural chromosome aberrations, chromosomal instability, increasing aneuploidy and initiates cervical carcinogenesis. The deregulated expression of the viral oncogene E7 is indicated by strong over-expression of the cellular p16(INK4a) gene product. This finding may have significant influence on novel strategies in cervical cancer diagnosis and screening. This review summarizes the basic molecular mechanisms of how papillomaviruses contribute to cellular transformation and how this can influence future diagnostic applications.

Pathologe. 2005 Jun 1

MICROBIOLOGY

Helicobacter heilmannii infection: Clinical, endoscopic and histopathological features in Japanese patients

Yoko Okiyama, Kenji Mtsuzawa, Eiko Hidaka et al

Gastric biopsy materials of 4074 consecutive Japanese patients undergoing esophagogastroduodenoscopy were reviewed, along with those of 15 patients with Helicobacter heilmannii infection (11, chronic gastritis; four, mucosa-associated lymphoid tissue (MALT) lymphoma). In four patients with H. heilmannii infection, the materials were examined by transmission electronmicroscopy. Urea breath test (three patients) and antibody test (five patients) were performed in patients with H. heilmannii infection. In two patients with MALT lymphoma, H. heilmannii was eradicated. The prevalence of H. heilmannii was 0.1% in the consecutive series. In chronic gastritis, the gastric mucosa was endoscopically normal (13.3%), had erythema (33.3%), or had erosions (53.3%); histologically, it showed no epithelial change, mild mononuclear cell infiltration, and slight and focal neutrophil infiltration; Helicobacter heilmannii was positive with anti-H. pylori antibody, and was detected in the mucous gel layer and in foveolae. In MALT lymphoma, the gastric mucosa was coarsely granular with enlarged mucosal folds without ulcers (two cases), with small ulcers (one case), or with multiple erosions (one case). Urea breath test and antibody test were both negative. Eradication of H. heilmannii resulted in remission of MALT lymphoma. Helicobacter heilmannii infection is therefore uncommon in Japanese adults, but is associated with chronic gastritis and gastric MALT lymphoma.

Pathology International, Volume 55 Issue 7 Page 398 - July 2005


		June 2005
		ANATOMIC PATHOLOGY Gestational Trophoblastic Diseases: Recent Advances in Histopathologic Diagnosis and Related Genetic Aspects Hui, Pei , Martel, Maritza ,Parkash, Vinita Gestational trophoblastic disease refers to a spectrum of proliferative disorders of the placental trophoblast, with a wide range of histologic appearances and clinical behaviors. This review discusses the more recent developments in the diagnosis of these entities. Changes in criteria for the histologic diagnosis of these lesions due to earlier clinical diagnosis are reviewed, and the ability to make more accurate diagnoses due to the introduction of newer antibodies such as p57 is highlighted. A discussion of epithelioid trophoblastic tumor, a newly introduced tumor subtype, with its differential diagnosis from placental-site trophoblastic tumor and squamous cell carcinoma is also presented. Last, a brief discussion on the role of genetic studies and the future direction of research in elucidating the nature of this intriguing group of lesions is presented. Advances in Anatomic Pathology. 12(3):116-125, May 2005. Seminoma: A Review With Emphasis on Morphologic Patterns and Differential Diagnosis Henley, John D. , Ulbright, Thomas M. Seminoma can manifest a variety of different growth patterns. A solid or nested pattern is the most common and readily recognized. Other patterns include trabecular/cordlike, cribriform/microcystic, tubular and intertubular, several of which may lead to diagnostic confusion with a variety of other tumors. A trabecular or cordlike pattern is common at the periphery of solid/nested areas and is usually not a diagnostic issue. A microcystic/cribriform arrangement, often but not always secondary to intercellular edema, is less common and may be mistaken for yolk sac tumor. The absence or paucity of lymphocytic inflammation in many cases further complicates recognition. A conspicuous pattern of solid or hollow tubules in seminoma may resemble Sertoli cell tumor or an epithelial neoplasm. Finally, an intertubular pattern of growth, common at the periphery of solid/nested seminoma, rarely occurs in a pure form. Purely intertubular tumors have uncommon clinicopathologic features, including absence of a testicular mass, both clinically and on gross examination, and microscopically obscure tumors. The latter occur within a background of tubular atrophy and sclerosis. In all morphologic patterns of seminoma, the tumor cells retain a characteristic appearance. They are large, 15 to 25 [mu]m, rounded, or polyhedral. Cell borders are typically crisp and distinct. Cytoplasm is usually clear or finely granular, and cytoplasmic glycogen is demonstrable on periodic acid-Schiff stain. Occasionally, cells may acquire a plasmacytoid morphology, with densely staining, amphophilic cytoplasm, and a degree of nuclear eccentricity, which complicates the distinction from lymphoma and plasmacytoma. Some cases may show a focal signet ring cell appearance. T cells dominate the lymphoid infiltrates that occur to some extent in virtually all seminomas. Granulomatous inflammation, occurring in up to 50% of cases, varies from ill-defined clusters of epithelioid histiocytes to well-formed granulomas with Langhans-like giant cells. In a fifth of cases, granulomatous inflammation is intense, with potential effacement of virtually all of the neoplastic cells, and such cases must be distinguished from granulomatous orchitis. Up to 20% of usual seminomas contain true syncytiotrophoblast giant cells, which stain positively for human chorionic gonadotropin. Their presence, like the degree of mitotic activity in seminoma, has no established bearing on prognosis. When trophoblast cells are prominent and associated with "blood lakes," misinterpretation as choriocarcinoma may occur. When the diagnosis is in doubt, immunohistochemistry is useful in recognizing all patterns of seminoma and aiding discrimination from other diagnostic considerations. Seminomas stain positively for placental alkaline phosphatase, Oct 3/4, and c-Kit (CD117) and are generally negative for cytokeratins; a panel of immunostains that contains these markers usually suffices to confirm or refute a diagnosis of seminoma. Pathology Case Reviews. 10(4):167-175, July/August 2005. Ectopic Decidua of Pelvic Lymph Nodes: A Potential Diagnostic Pitfall Debbie C. Wu, Sharon Hirschowitz, Sathima Natarajan Ectopic decidua is one of several benign lymph node inclusions that have been increasingly documented in the literature, most often in postmortem examinations of pregnant woman and recently in pregnant women with cervical squamous cell carcinoma. Although lacking clinical significance of its own, the major diagnostic implication would be misdiagnosis as metastatic carcinoma in the lymph node. Intraoperative frozen sections are often performed prior to radical hysterectomy, leading to a potential alteration of therapy if metastatic carcinoma is identified in the lymph nodes. Authors report such a case of a pregnant woman with cervical squamous cell carcinoma requiring lymphadenectomy and hysterectomy, in which the intraoperative frozen section of a pelvic lymph node with ectopic decidual change was mistakenly identified as metastatic carcinoma. Its histologic resemblance to carcinoma and location within subcapsular sinuses, compounded with the fact that ectopic lymph node decidua is not commonly seen in routine practice, can lead to this diagnostic pitfall. Authors review the literature regarding ectopic decidua, its presence in lymph nodes, and its pathogenesis, as well as review the literature on benign lymph node inclusions. Although ectopic decidua has been sporadically reported in the literature, pathologists have few opportunities to examine lymph nodes in pregnant or postnatal women, therefore raising the possibility that it may be overlooked or misidentified. In addition to ectopic decidua, there are a number of other types of benign lymph node inclusions, which although usually incidental, may pose diagnostic dilemmas. This diagnostic pitfall may become especially relevant during frozen section examination. Therapy for cervical squamous carcinoma not uncommonly includes intraoperative frozen section examination of pelvic and paraaortic lymph nodes prior to radical hysterectomy, with the presence of metastases as a potential reason for aborting the procedure and thus altering the course of therapy. Therefore, recognition of the presence of benign lymph node inclusions, most notably ectopic decidua, should be raised. Archives of Pathology and Laboratory Medicine: Vol. 129, No. 5, pp. e117e120 Localized Malignant Mesothelioma Allen TC, Cagle PT, Churg AM et al Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior.Authors report 23 new cases. The mean age at presentation was 63 years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of the tumor, 10 of 21 patients with follow-up data were alive without evidence of disease from 18 months to 11 years after diagnosis. Patients who died had developed local recurrences and metastases, but none had diffuse pleural spread. Localized malignant mesotheliomas should be separated from diffuse malignant mesotheliomas because of their localized presentation, quite different biologic behavior, and far better prognosis. Am J Surg Pathol. 2005 Jul;29(7):866-873. Inflammatory myofibroblastic tumor of the breast Elham Khanafshar, Julia Phillipson, et al Three patients developed firm, mobile, nontender masses in their breasts. Two were discovered by the patients and one after mammography. Macroscopically, the nodules were firm, circumscribed, yellow on cut sections, and composed of interlacing cytologically bland spindle cells admixed with chronic inflammatory cells, the latter predominantly of lymphocytes and plasma cells. Immunohistochemistry yielded strong smooth-muscle actin reactivity within the spindle cells; 2 lesions were negative for pankeratin, 1 was focally and weakly positive. No lesions were positive for anaplastic lymphoma kinase-1, desmin, S-100, CD34, CD21, or CD35. In each case, a diagnosis of inflammatory myofibroblastic tumor was made (aka, inflammatory pseudotumor). After conservative excision with apparently negative margins, there have been no recurrences, except in one patient who developed a recurrence after 3 months. The latter recurrence was managed successfully with a second excision. Authors report these patients to emphasize the diagnostic features of inflammatory myofibroblastic tumor of the breast and discuss how they can be distinguished from other spindle-cell breast lesions with which they can be confused, especially spindle-cell carcinoma. Annals of Diagnostic Pathology, June 2005 Volume 9 Number 3 Immunohistochemical detection of cdc2 is useful in predicting survival in patients with mantle cell lymphoma Hui D, Reiman T, Hanson J et al Recent cDNA microarray studies have reported the prognostic value of several genes in mantle cell lymphoma patients. Authors aimed to validate the prognostic significance of three of these genes: alpha-tubulin, cdc2, and CENP-F. The protein expression of alpha-tubulin, cdc2, and CENP-F was assessed using immunohistochemistry. Their immunoreactivity in 48 formalin-fixed/paraffin-embedded mantle cell lymphoma tumors was determined by estimating the percentage of positive cells. These results were correlated with the expression of proliferation marker Ki67 and survival. Of these 48 mantle cell lymphoma patients, 41 were men and seven were women. The median age at time of diagnosis was 64.5 years, and the overall median survival was 40 months. In benign lymph nodes, the expression of cdc2 and alpha-tubulin was restricted to the germinal centers; mantle zones were negative. Expression of CENP-F was more uniformly distributed. In mantle cell lymphoma, Ki67 significantly correlated with all three markers (P<0.05, Spearman), but only Ki67 (>50%) and cdc2 (>25%) significantly correlated with shorter survival (P<0.0006, Spearman). Of several clinical parameters examined, international prognostic index of >/=2 correlated with worse clinical outcome, and high clinical stage (ie 4 vs </=3) showed a trend for shorter survival. The prognostic significance of cdc2 and Ki67 was independent of international prognostic index and clinical stage. We have validated the prognostic value of cdc2, and confirmed that of Ki67, in a cohort of mantle cell lymphoma patients. Immunohistochemical detection of cdc2 and Ki67 may be a useful and simple method in evaluating the prognosis of mantle cell lymphoma patients. Mod Pathol. Jun 3, 2005 Basal cell hyperplasia: An unusual diagnostic dilemma on prostate needle biopsies Hosler GA, Epstein JI. Basal cell hyperplasia (BCH) is a well-recognized entity on transurethral resection specimens, but it is an uncommon finding on prostatic needle biopsies, and the diagnostic difficulties with it have not been fully defined on this material. A 13-year (1991-2003) retrospective review of the consult files of one of the authors was performed. In all cases, the focus of BCH was referred for consultation to rule out adenocarcinoma. Thirty-three cases of prominent BCH were identified. The dominant pattern of BCH consisted of either glands (26/33) or solid nests (7/33). Other minor patterns included cribriform (5), pseudocribriform (4), cords (1), and adenoid basal (1). Twelve of 33 cases showed an infiltrative pattern. Other features of BCH included prominent nucleoli (14/33), abnormal secretions (17/33 with dense pink and/or blue mucin), mitoses (6/33), altered stroma with increased cellularity (6/33), calcifications (6/33), intraluminal crystalloids (3/33) and perineural invasion (1/33). By immunohistochemistry, 7 (100%) out of 7 were positive for p63 and 14 (88%) of 16 were positive for high molecular weight cytokeratin. No cases (0/6) were positive for alpha-methylacyl-coenzyme A racemase. Basal cell hyperplasia, as a mimicker of cancer, is an uncommon entity encountered on prostatic needle biopsies. Helpful features for its diagnosis include solid nests, pseudocribriform glands, multilayering of cells, calcifications, and cellular stroma. Immunohistochemistry can be useful for documenting the basal cell layer and demonstrating negative racemase staining. Hum Pathol. 36(5):480-5-2005 Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literature M Varma & B Jasani Immunohistochemistry is widely used to distinguish prostate cancer from benign mimics and to establish the prostatic origin of poorly differentiated carcinoma. Authors critically reviewed the recent advances in prostate cancer immunohistochemistry, including the introduction of newer basal cell markers such as p63 and the discovery of the overexpression of -methylacyl coenzyme A racemase (AMACR) in prostate cancer. The description of newer urothelial markers to aid the distinction of prostate cancer from urothelial carcinoma is also presented together with refinements in the quality control of PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical marker for prostate cancer, it has significant limitations. These limitations are discussed and the need for interpreting AMACR immunoreactivity in the appropriate morphological context and in conjunction with basal call markers is emphasized. Authors also describe the utility of an immunohistochemical panel composed of PSA, PSAP and high molecular weight cytokeratin for distinguishing poorly differentiated prostate cancer from high-grade urothelial carcinoma. A morphological differential diagnosis based selection of immunohistochemical markers is highlighted as a novel approach in the diagnosis of prostate cancer in routine surgical pathology practice. Histopathology,Vol. 47 Issue 1 Page 1 - July 2005 Molecular pathogenesis of cervical cancer Article in German Trunk MJ, Wentzensen N, von Knebel Doeberitz M. Specific types of the human papillomaviruses (high risk human papillomaviruses) play an essential role in the pathogenesis of cervical cancer. Although infections by these viruses are very common in the general population, only few result in clinically relevant lesions. Continuous and deregulated expression of two viral oncoproteins E6 and E7 in basal or parabasal cells are required to induce and maintain neoplastic growth. In the course of an acute HPV-infection these genes are exclusively expressed in cell cycle arrested, terminally differentiated cells in the intermediate or superficial layers of the epithelium. Accidental activation of these genes in proliferating cells in the basal or parabasal cell layers results in interference with the cell cycle regulation, disturbances of the mitotic spindle apparatus and centrosome functions. This results in numerical and structural chromosome aberrations, chromosomal instability, increasing aneuploidy and initiates cervical carcinogenesis. The deregulated expression of the viral oncogene E7 is indicated by strong over-expression of the cellular p16(INK4a) gene product. This finding may have significant influence on novel strategies in cervical cancer diagnosis and screening. This review summarizes the basic molecular mechanisms of how papillomaviruses contribute to cellular transformation and how this can influence future diagnostic applications. Pathologe. 2005 Jun 1 MICROBIOLOGY *Helicobacter heilmannii* infection: Clinical, endoscopic and histopathological features in Japanese patients Yoko Okiyama, Kenji Mtsuzawa, Eiko Hidaka et al Gastric biopsy materials of 4074 consecutive Japanese patients undergoing esophagogastroduodenoscopy were reviewed, along with those of 15 patients with Helicobacter heilmannii infection (11, chronic gastritis; four, mucosa-associated lymphoid tissue (MALT) lymphoma). In four patients with H. heilmannii infection, the materials were examined by transmission electronmicroscopy. Urea breath test (three patients) and antibody test (five patients) were performed in patients with H. heilmannii infection. In two patients with MALT lymphoma, H. heilmannii was eradicated. The prevalence of H. heilmannii was 0.1% in the consecutive series. In chronic gastritis, the gastric mucosa was endoscopically normal (13.3%), had erythema (33.3%), or had erosions (53.3%); histologically, it showed no epithelial change, mild mononuclear cell infiltration, and slight and focal neutrophil infiltration; Helicobacter heilmannii was positive with anti-H. pylori antibody, and was detected in the mucous gel layer and in foveolae. In MALT lymphoma, the gastric mucosa was coarsely granular with enlarged mucosal folds without ulcers (two cases), with small ulcers (one case), or with multiple erosions (one case). Urea breath test and antibody test were both negative. Eradication of H. heilmannii resulted in remission of MALT lymphoma. Helicobacter heilmannii infection is therefore uncommon in Japanese adults, but is associated with chronic gastritis and gastric MALT lymphoma. Pathology International, Volume 55 Issue 7 Page 398 - July 2005
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