[Male genitourinary system lymphoma: a clinicopathological analysis].

OBJECTIVE: To investigate the clinicopathological features and immunophenotypes of male genitourinary system lymphoma. METHODS: We retrospectively studied the histopathological characteristics and immunohistochemical markers of 35 cases of male genitourinary system lymphoma, and reviewed the relevant literature. RESULTS: The 35 patients of male genitourinary system lymphoma were aged from 4 to 83 (mean 56.5) years, 28 (80%) of them > or = 50 years. Twenty-eight cases (80%) involved the testis, 3 (8.6%) the prostate, 1 (2.9%) the spermatic cord, 1 the seminal vesicles, 1 the penis and 1 the epididymis. Histologically, 22 cases (62.9%) were diffused large B cell lymphoma (DLBCL), 6 (17.1%) mucosa associated lymphoid tissue (MALT) lymphoma, 4 (11.4%) Burkitt lymphoma, 2 (5.7%) peripheral T cell lymphoma, and 1 (2.9%) plasmacytoma. CONCLUSION: Male genitourinary system lymphomas are rare tumors clinically, which occur more often in the elderly. The majority of them are B cell lymphomas, of which the most common is DLBCL, followed by MALT lymphoma and Burkitt lymphoma. T cell lymphoma and plasmacytoma are rare. The diagnosis of male genitourinary system lymphoma relies on the histopathology, and immunohistochemical markers are of high value for its definite diagnosis, classification and differential diagnosis.

[Mucinous tubular and spindle cell carcinoma of kidney: a clinicopathological study].

OBJECTIVE: To investigate the clinicopathological features, histogenesis and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC). METHODS: Five MTSCCs were studied with histochemical, immunohistochemical staining, electron microscopy, and review of the related literatures. RESULTS: Four cases of MTSCC were females and one was male. Three patients presented with flank discomfort and two were incidentally found with health examination. In gross examination, the tumors were circumscribed. The cut surface was solid, gray-white, yellow or red. Necrosis was present in one case of high-grade MTSCC. Microscopically, low-grade MTSCC was mainly consisted of tubular, spindle cell and mucinous stroma with relatively bland morphology, and mitoses were rare. While in the high-grade area of one case, the cells were spindle or polymorphic with severe atypia and high mitotic activity, without mucinous stroma and tubular structure. Mucin was positive for Alcian blue. The neoplastic cells were positive for vimentin (5/5), CKpan (5/5), CK7 (5/5), CK19 (5/5), 34betaE12 (1/5), EMA (5/5), E-cadherin (3/5), CD10 (1/5), P504S (5/5), and CAM5.2 (5/5). The Ki-67 index was low (< or = 5%) in the low-grade component, while it was high (15%) in the high-grade component. Ultrastructural study showed short microvilli along glandular lumens. The nuclear membrane was focally invaginated. Four cases were followed up for 3 to 52 months, and recurrence and metastasis were not found. CONCLUSIONS: MTSCC occurs predominantly in females and it is a rare kidney neoplasm. Most of MTSCCs are low-grade and the prognosis is relatively good. However, the patients of high-grade MTSCC should be closely followed up.

[Expression of ID3 protein in prostate cancer and its clinicopathological significance].

OBJECTIVE: To study the expression of the ID3 protein in prostate cancer and its clinicopathological significance. METHODS: We detected the expression of the ID3 protein in PC-3M cells by indirect immunofluorescence, and that in 29 prostate cancer and 15 prostate hyperplasia specimens by immunohistochemistry. Then we analyzed the correlation between the expression level of ID3 and the clinicopathological parameters. RESULTS: The ID3 protein was expressed predominantly in the nucleus of PC-3M cells. Its expression rate was 82.7% (24/29) in the prostate cancer specimens, significantly higher than 6.6% (1/15) in prostate hyperplasia (P < 0.05), and was positively correlated with the Gleason score of prostate cancer (P < 0.05). CONCLUSION: The ID3 protein is expressed in prostate cancer, and is elevated with the increase of Gleason score.

Primary kaposiform hemangioendothelioma of a long bone: two cases in unusual locations with long-term follow up.

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm of low malignant potential that mainly affects infants and adolescents. The tumor almost exclusively occurs in somatic soft tissue or the retroperitoneum. We report herein two cases of primary KHE occurring in a long bone without cutaneous changes with long-term follow up in young patients. The patients were a 9-year-old girl and 5-year-old boy presenting with lytic lesions of the femur and humerus, respectively, without cutaneous lesions. Histologically, the neoplasms were comprised of nodules of spindle- to oval-shaped cells growing in an infiltrative fashion. The neoplastic cells formed poorly canalized or slit-like blood vessels alternating with solid spindle areas. Immunohistochemical studies showed that the tumor cells expressed CD31, CD34 and Fli1, but not HHV8, LNA-1 or GLUT1. D2-40 stained the neoplastic spindle cells and lymphatic channels adjacent to vascular lobules. The girl remains well with 15 years and 6 months follow up after a second complete excision. The boy has no signs of recurrence or metastasis nearly 5 years after local complete excision. To our best knowledge, this is the first report in the English literature of primary long bone occurrences of KHE without cutaneous changes with long-term follow up.

[Clinicopathological analysis of testicular mixed germ cell tumor].

OBJECTIVE: To investigate the clinicopathological characteristics of primary testicular mixed germ cell tumor (MGCT). METHODS: We retrospectively analyzed the clinicopathological data of 13 cases of primary testicular MGCT and reviewed other relevant literature. RESULTS: MGCT accounted for 24.1% (13/54) of all the testicular germ cell tumors diagnosed in our hospital. The patients ranged in age from 2 to 53 years, averaging at 28.3 years. All were unilateral cases, 6 in the left and 7 in the right testis, with a left/right ratio of 0.86:1. Morphologically, testicular MGCT displayed a variety of subtypes, embryonal carcinoma in 11 cases (84.6%), seminoma in 8 (61.5%), teratoma in 6 (46.2%), choriocarcinoma in 4 (30.8%) and yolk sac tumor in 4 (30.8%). Nine of the cases (69.2%) were composed of two different germ cell histological elements, 3 (23.1%) composed of three, and 1 (7.7%) composed of five. CONCLUSION: Testicular MGCT is rather rare and most commonly occurs in young men. Its biological behavior, clinical management and prognosis vary with its different histological elements. Therefore accurate pathological diagnosis is essential and immunohistochemistry plays an important role in the diagnosis and differential diagnosis of testicular MGCT.

Renal cell carcinoma in children and young adults: clinicopathological, immunohistochemical, and VHL gene analysis of 46 cases with follow-up.

To further study the characteristics of renal cell carcinoma (RCC) in young patients and better define their biological features, 46 RCCs of patients younger than 25 years were morphologically and immunohistochemically characterized with follow-up. Loss of heterozygosity (LOH) analysis of the von Hippel-Lindau (VHL) gene region and screening for VHL gene mutations were performed in all tumors. Applying the 2004 WHO classification for RCC, there were 19 Xp11.2 translocation RCCs, 9 clear cell RCCs, 17 papillary RCCs, and 1 unclassified RCC. All 19 Xp11.2 translocation RCCs showed moderate to strong immunoreactivity for TFE3. None had TFEB immunoreactivity. One Xp11.2 translocation RCC had an unreported morphology with empty or ground glass nuclei, occasional nuclear grooves, inconspicuous nucleoli and abundant mucinous material in stroma.VHL gene analysis revealed deletions at 3p25-26 in 1 clear cell RCC and 1 papillary type 2 RCC. The papillary type 2 RCC was also presented with a family history of VHL disease and found a germline mutation G → C on a splicing site at position 553+5. The present case widens the spectrum of microscopic features to be found in VHL-associated RCC. There were no VHL mutations in the remaining 45 RCCs. Statistical analysis of stage and outcome revealed that TFE+ pediatric RCCs were significantly more frequently associated with a higher pTNM pT3/pT4 stage and a poorer outcome than TFE-RCCs (P < .05). Owing to the already known aggressive behavior of these Xp11.2 translocation RCCs, patients with TFE+ pediatric RCCs should benefit from a stricter follow-up.

[Clinicopathologic and molecular genetic study of renal cell carcinoma occurring in teenagers].

OBJECTIVE: To investigate clinicopathological features, molecular genetic characteristics, differential diagnoses and prognosis of renal cell carcinoma in teenagers. METHODS: Microscopic and immunohistochemical features of 46 cases of renal cell carcinomas in teenagers were reviewed along with the clinical follow-up data. Loss of heterozygosity (LOH), analysis of von Hippel-Lindau (VHL) gene and screening for VHL gene mutations were performed in all of the tumors. RESULTS: There were 19 Xp11.2 translocations/TFE3 gene fusions renal clear cell carcinomas (Xp11 RCCs), 9 chromophobe renal cell carcinomas (CCRCCs), 17 papillary renal cell carcinomas (PRCCs), and 1 unclassified renal cell carcinoma (RCC). All of the 19 Xp11.2 translocation RCCs showed a moderate to strong immunoreactivity for TFE, however, no TFEB expression was obtained. There were 4 histological patterns in the Xp11 RCC cases including: 8 tumors possessing a nested to papillary architecture resembling to the t(X;17) ASPL-TFE3 phenotype; 6 tumors possessing a morphologic feature like the t(X;1) PRCC-TFE3 phenotype; 4 cases morphologically resembling to clear cell RCC; and 1 Xp11 RCC case, with a special morphologic feature not searched yet in the literature, including a ground glass appearance of the nuclei accompanying occasionally with grooves on the nuclear surface; nucleoli inconspicuous with accumulation of abundant mucin-like substance in the stroma. VHL gene analysis revealed deletions at 3p25-26 in one clear cell RCC and one papillary type 2 RCC. The papillary type 2 RCC had also a family history of VHL disease, with a germline G→C mutation at a splicing site of position 553+5. There were no VHL mutations detected in the remaining 45 RCCs. Statistical analysis of tumor stage and outcome revealed that TFE+ RCCs of teen-agers were more frequently associated with a higher pT3/pT4 stage and a poorer outcome than that of the TFE-RCCs (P < 0.05). CONCLUSIONS: RCCs of the teenagers have a different morphologic spectrum and genetic background from the RCCs seen in adults. Among RCCs of the teen-agers, Xp11.2 translocation tumors are the most common RCCs and have a poorer prognosis than that of the TFE-RCCs.

[Expression of CD20 in thymomas and its clinical implication].

OBJECTIVE: To study the expression of CD20 in thymomas and its clinical significance. METHODS: One hundred and seventy-nine cases of thymoma were enrolled into the study. The histologic diagnosis was reviewed by two experienced pathologists on the basis of the 2004 WHO classification. One hundred and two cases were selected for immunohistochemical study for CD20, pancytokeratin, TdT, CD3, CD43, CD99 and S-100 protein. The cases were further categorized into two groups, according to the association with clinical evidence of myasthenia gravis. The immunostaining pattern was then statistically analyzed. RESULTS: Amongst the 102 cases studied, 7 cases belonged to type A thymoma, 32 cases type AB thymoma, 17 cases type B1 thymoma, 15 cases type B2 thymoma, 17 cases type B3 thymoma and 14 cases thymic carcinoma. The expression rates of CD20 in neoplastic epithelial cells of type A, type AB, type B1, type B2 and type B3 thymomas and thymic carcinomas were 3/7, 84.4% (27/32), 1/17, 2/15, 0/17, 0/14, respectively. The proportions of CD20-positive lymphocytes in the background were 3/7, 18.8% (6/32), 14/17, 11/15, 11/17, 6/14, respectively. The proportion of CD20-positive intra-tumoral B lymphocytes in the group of thymomas with myasthenia gravis was 67.5% (22/40), in contrast to 35.5% (22/62) in those without myasthenia gravis. CONCLUSIONS: The neoplastic epithelial cells in cases of type A and type AB thymoma, as well as few cases of type B1 and B2 thymoma, express CD20. The immunostain highlights the presence of oval, stellate or spindly cells. Thymomas associated with myasthenia gravis contain a significant population of CD20-positive intra-tumoral B lymphocytes. Type AB thymomas may be originated from different populations of cells, rather than a simple admixture of type A and B thymoma cells.

Relationship between RGS5 expression and differentiation and angiogenesis of gastric carcinoma.

AIM: To explore the regulator of G-protein signaling 5 (RGS5) expression in gastric carcinoma and its association with differentiation and microvascular density (MVD). METHODS: Expression of RGS5 and CD34 were examined in 76 cases of gastric carcinoma, including 22 cases with lymph node metastasis and 54 cases without lymph node metastasis determined by immunohistochemistry (IHC). MVD was assessed using CD34 monoclonal antibody. The presence of RGS5 and CD34 was analyzed by IHC using the Envision technique. RESULTS: The RGS5 expression in gastric carcinoma was positively correlated with the differentiation of the tumor (r = 0.345, P < 0.001), but not related with age, gender, tumor size, clinical stage and lymph node metastasis (P > 0.05). The average MVD in the group with lymph node metastasis was significantly higher than that in the group without lymph node metastasis (P < 0.05). RGS5 expression was negatively correlated with the average MVD (P < 0.05). CONCLUSION: RGS5 expression level in gastric carcinoma is associated with the differentiation and MVD of the tumor, and may be used as an important parameter for determining the prognosis of gastric carcinoma patients.

Expression analysis of Wnt-5a in renal epithelial neoplasms: distinguishing renal oncocytoma from a wide spectrum of renal cell carcinomas.

OBJECTIVE: To study the expression of a novel marker, Wnt-5a, in renal epithelial neoplasms and determine its clinicopathological significance. METHODS: Immunohistochemical analysis of Wnt-5a was carried out in normal human kidney samples as well as in 123 primary renal epithelial neoplasms including 37 clear cell renal cell carcinomas (RCCs), 24 papillary RCCs (15 type 1 and 9 type 2), 25 chromophobe RCCs, 11 Xp11 translocation carcinomas, 6 mucinous tubular and spindle cell carcinomas, and 20 oncocytomas. RESULTS: Wnt-5a was expressed in 18.9% (7/37) of clear cell RCCs, 12.5% (3/24) of papillary RCCs, 16% (4/25) of chromophobe RCCs, 18.2% (2/11) of Xp11 translocation carcinomas, 0% (0/6) of mucinous tubular and spindle cell carcinomas, and 100% (20/20) of oncocytomas. There was a significant difference in Wnt-5a immunohistochemistry between renal oncocytoma and the other subtypes of RCC (P < 0.01). CONCLUSIONS: Our results indicate that Wnt-5a is a potentially useful immunohistochemical marker for the complex differential diagnosis between oncocytoma and other subtypes of RCC and also suggest that Wnt-5a may be a tumor suppressor gene in RCC.

[Clinicopathologic study of von Hippel-Lindau syndrome-related and sporadic hemangioblastomas of central nervous system].

OBJECTIVE: To study clinicopathologic features, diagnosis, treatment and prognosis of von Hippel-Lindau (VHL) syndrome-related and sporadic hemangioblastomas of the central nervous system (CNS-HB). METHODS: Histopathological, ultrastructural, immunohistochemical (EnVision method) and clinical features of 21 VHL syndrome and 63 sporadic CNS-HB cases were studied with correlation of the available follow-up information. RESULTS: Twenty-one VHL patients accompanied with a total of 87 CNS-HBs, including one patient of developing 12 HBs within 13 years. There were 10 patients presenting other lesions related to VHL, including 6 retinal HBs, 4 pancreatic tumors (endocrine tumor and microcystic cystadenoma), 1 clear renal cell carcinoma, 4 renal cysts and 1 endolymphatic sac tumor. One patient developed 5 different tumors related to VHL within a period of 4 years. In the 63 cases of sporadic CNS-HB (34 male and 29 female), the mean age was 43.0 years. Among the 18 VHL syndrome patients with available follow-up information, 14 were still alive and within them, 4 became disabled and 11 had developed new lesions. The other 4 patients died. Among the 42 patients of sporadic HB with follow-up information, 39 were alive including 3 disabled cases, and the other 3 died. Histologically, the tumors showed large and vacuolated stromal cells. Some tumors showed atypical nuclei. Involvement of the brain tissue was seen in 32 cases, among which, 21 patients with available follow-up information were learnt to be alive. Tumor cells of HB stained positive for vimentin, EGFR, Inhibin alpha and D2-40, but negative for CD34 and CD68. In 3 cases of HB, some stromal cells were positive for GFAP. All cases showed a low expression for Ki-67, except 2 cases with 2% and 1 case with 5% Ki-67 indices. CONCLUSIONS: VHL syndrome is a multisystem disorder with a poor prognosis and a high rate of missed diagnosis. The syndrome is characterized by development of various benign and malignant tumors. The most common tumor is CNS-HB, which occurs predominantly in the cerebellum. Patients with VHL syndrome tend to present at a younger age than patients with sporadic CNS-HBs, and VHL related HB occurs more predominantly in the brain stem and spinal cord. Prognosis of CNS-HB patients is not correlated with the nuclear atypicality, expression for Ki-67 and involvement of the brain tissue. Because new lesions may develop during the patient's lifetime. So that, regular clinical inspection is recommended in order to check up the development of any new lesions.

[Clinicopathologic features of granulocytic sarcoma: a study of 38 cases].

OBJECTIVE: To study the clinicopathologic features of granulocytic sarcoma. METHODS: The clinical and pathologic findings of 38 cases of granulocytic sarcoma were retrospectively analyzed. Immunohistochemical study was performed and the literature was reviewed. RESULTS: The age of patients ranged from 2 to 77 years (mean = 43.3 years). The male-to-female ratio was 1.5:1. Major clinical presentations included superficial lymph node enlargement and painful soft tissue mass. Follow-up data were available in 18 patients; and 14 of them died of tumor-related diseases. The average duration of survival of the patients was 16.9 months. Histologically, the tumor cells were relatively uniform in appearance and small to medium in size. The cytoplasm was scanty and pale in color. The nuclei were round or focally irregular, with fine chromatin and inconspicuous nucleoli. Mitosis figures were readily identified. Scattered immature eosinophilic myelocytes were seen. Immunohistochemical study showed that the tumor cells in all cases expressed MPO and CD43. Most cases were also positive for CD68, lysozyme, CD99 and TdT. The staining for CD3, CD20, CD79a, pan-cytokeratin and PLAP were negative. CONCLUSIONS: Granulocytic sarcoma is a known histologic mimicker of non-Hodgkin lymphoma, Ewing sarcoma/PNET and embryonal rhabdomyosarcoma. Detailed morphologic examination, when coupled with immunohistochemical study, is useful in arriving at a correct diagnosis.

[Expression and clinical significance of kidney injury molecule-1 in renal epithelial neoplasms].

OBJECTIVE: To study the expression and clinical significance of kidney injury molecule-1 (KIM-1) in primary and metastatic renal epithelial neoplasms. METHODS: A total of 136 cases of kidney neoplasms were retrospectively reviewed including 63 primary clear cell renal cell carcinomas (RCCs), 22 papillary RCCs, 13 chromophobe RCCs, 7 oncocytomas, 7 RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 24 metastatic clear cell RCCs. Immunostaining for KIM-1 and kidney-specific-protein (Ksp)-cadherin were performed and the relationship to tumor stage and grade in clear cell RCCs was investigated. RESULTS: Expression of KIM-1 was detected in 77.8% (49/63) of clear cell RCCs, 90.9% (20/22) of papillary RCCs, 1/13 of chromophobe RCCs, 7/7 of RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 87.5%(21/24) of the metastatic RCCs, but not detected in 7 cases of oncocytomas. A diffuse expression of KIM-1 was more frequently observed in Furhman nuclear grade III/IV clear cell RCCs (P = 0.010). Ksp-cadherin expression was mainly observed in chromophobe RCCs and oncocytomas. CONCLUSIONS: KIM-1 is a specific biomarker for injuried kidney proximal tubules and the corresponding neoplasms, and has a high specificity and sensitivity for primary or metastatic clear cell RCCs, papillary RCCs and RCCs associated with Xp11.2 translocation/TFE3 gene fusions. Combination of KIM-1 and Ksp-cadherin immunostaining can lead to a more precise histological classification of primary kidney epithelial neoplasms and improve the diagnostic accuracy of metastatic RCCs.

[Primary Burkitt lymphoma of the seminal vesicle: a case report and review of the literature].

OBJECTIVE: To investigate the clinicopathological features of primary Burkitt lymphoma of the seminal vesicle. METHODS: We reported the clinical characteristics, histological changes and the results of immunohistochemical staining and molecular in situ hybridization of 1 case of primary Burkitt lymphoma of the seminal vesicle. We also reviewed the related literature and studied the pathomorphological characteristics and differential diagnosis of the tumor. RESULTS: The characteristic manifestations of the patient were frequent micturition with dysuria, followed by inguinal lymphadenectasis 2 months later. Medical imaging showed a diffuse and monotonous infiltration of neoplastic cells with scanty cytoplasm and a few mitosis images. Microscopy displayed a starry sky pattern. The tumor cells were positive for CD10, CD20, CD79alpha, Bcl-6 and EBER in situ hybridization, but negative for CD3, CD6 and Cyclin D1. The Ki-67 index was > 95%. CONCLUSION: Primary Burkitt lymphoma of the seminal vesicle is a very rare tumor with aggressive behavior. The pathological diagnosis of the tumor depends on histopathological examination and immunohistochemical techniques. However it should be differentiated from diffuse large B-cell lymphoma, lymphoblastic lymphoma and small cell carcinoma of the seminal vesicle or prostate gland.

[Clinicopathological study of 5 cases of proximal-type epithelioid sarcoma].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis and differential diagnoses of proximal-type epithelioid sarcoma (PES). METHODS: Five cases of PES were retrieved from pathology files. Clinical, pathologic and immunohistochemical features of the tumors were reviewed. RESULTS: One patient was female and 4 were male. Ages of the patients ranged from 19 to 46 years. The sites of the tumor involvement were vulvar (2 cases), hypogastric zone (1 case), anterosuperior iliac spine (1 case) and buttock (1 case). Clinically, the tumor masses were painless and progressive solitary nodules. Microscopically, the tumor cell growth was infiltrative in nature, nodular in appearance with degenerative and necrotic cells at the central areas. The tumors consisted of relatively uniform epithelioid cells with round or oval nuclei and eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for vimentin (5/5), CK (4/5), EMA (4/5), beta-catenin (3/5), CD34 (3/5), and S-100 protein (1/5), but were negative for SMA, MyoD1, Desmin, HMB-45, CK7 and CK20. CONCLUSION: Definitive diagnosis of PES relies on its histopathological characteristics in conjunction with appropriate immunohistochemical findings.