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Primary cutaneous large cell lymphomas. Morphologic, immunophenotypic, and clinical features of 20 cases.

The morphologic, immunophenotypic, and clinical characteristics of 20 cases of primary cutaneous large cell lymphoma were analyzed. Immunoperoxidase stains in paraffin sections indicated B-cell phenotype in 14 cases and T-cell phenotype in six cases. By the Kiel classification, the B-cell lymphomas were classified into the following categories: follicular centroblastic (three patients), centroblastic/centrocytic with a predominance of large centrocytes (two patients), centroblastic (seven patients), and immunoblastic (two patients). The T-cell lymphomas (six cases) were all categorized as pleomorphic medium and large cell type. Three of these had an angiocentric growth pattern. The lymphocyte activation marker CD30 was expressed in three of the 20 cases. Among these 20 patients, the clinical course was remarkably variable. The only clinical or pathologic feature with prognostic significance was multicentricity of the skin lesions. All five patients with multifocal or disseminated skin lesions died within 13 months of their initial presentation; the median survival was 7 months. Most of the patients with localized skin lesions had an indolent clinical course with a median survival of 107 months. These results suggest that multicentricity of the skin lesions and necrosis are closely linked and are important prognostic features in cutaneous large cell lymphoma.

Adult↗

Hepatic epithelioid hemangioendothelioma: biological questions based on pattern of recurrence in an allograft and tumor immunophenotype.

Epithelioid hemangioendothelioma (EHE) is best considered a vascular neoplasm of intermediate malignancy. Although usually progressive, the clinical course is highly unpredictable. The present communication describes a case of extensive recurrent hepatic EHE, limited to the liver allograft and initially manifest as an insidious seeding of individual tumor cells in areas of perivenular inflammation associated with rejection. A detailed immunophenotypic characterization of this and a small series of EHE was carried out in an effort to highlight subtle disease recurrence and to gain possible insights into tumor biology associated with this intriguing disease. In a series of five cases of hepatic EHE, CD34 (QB-END/10) was found to be more sensitive than Factor VIII (F-VIII) for recognition of the disease, similar to previous reports. The former diffusely and distinctly stained both epithelioid and dendritic tumor cells, whereas staining for the latter was focal, indistinct, and showed a high background. Although the tumor cells were negative for some markers of dendritic or macrophage maturation, such as CD1a, S100 protein, Mac 387, CD68, and LN3, there was marked infiltration of hepatic EHE by factor XIIIa + (F-XIIIa), Mac 387+, CD68+, and LN3+ macrophages and dendrocytes, most of which were interpreted as reactive. The "reactive" macrophage and dendrocyte populations were present throughout the fibrotic stroma and intermingled with the epithelioid clusters of EHE. Interestingly, a small subset of tumor cells coexpressed CD34 or F-VIII and F-XIIIa, the last of which is normally restricted to cells of the monocyte/macrophage lineage and cytokine activated microvascular endothelium in vitro. The known association of F-XIIIa+ dendrocytes with granulation tissue, repair and fibrogenesis, and the modulation of F-XIIIa and F-VIII expression by inflammatory cytokines led us to speculate that EHE lesions may derive from primitive "reticuloenothelial" cells that can differentiate along endothelial and dendritic pathways. The EHE lesions may represent a neoplastic analogue of wound healing. Thus, the variability in F-VIII staining, the strong expression of CD34, the infiltration of EHE lesions with F-XIIIa+ dendrocytes, and the coexpression of CD34 and F-XIIIa on a subset of tumor cells may have an important biological basis.

Antigens, CD34↗

The immunophenotypic spectrum of meningeal hemangiopericytoma: a comparison with fibrous meningioma and solitary fibrous tumor of meninges.

Despite controversy regarding its histogenesis, meningeal hemangiopericytoma (HPC) is a well-defined clinicopathologic entity exhibiting high rates of recurrence and late extracranial metastasis. It must be distinguished from several benign neoplasms, particularly fibrous meningioma (FM) and solitary fibrous tumor (SFT). To determine the immunoprofile of HPC, we studied 27 meningeal examples, including 13 low-grade and 14 high-grade tumors. For comparison, 20 FMs and eight SFTs of the meninges were also evaluated. The immunotype of HPC included vimentin (85%), factor XIIIa (78%) in individual scattered cells, Leu-7 (70%), and CD34 (33%) in a weak, patchy pattern. Focal desmin and cytokeratin positivity was only occasionally encountered (20% each). The SFT shared a similar immunophenotype, except that CD34 expression (100%) was characteristically strong and diffuse. The FM characteristically expressed epithelial membrane antibody (EMA) (80%) and S-100 protein (80%); CD34 reactivity (60%) was patchy and weak. Both within and among all three tumor types, MIB-1 labeling indices varied widely. Specifically, they were unrelated to tumor grade in HPC. Significant reactivity for p53 protein was detected in 52% of HPCs, 17% of SFTs, and 5% of FMs. Meningeal HPC exhibits a distinct antigenic profile, one enabling the exclusion of other entities in nearly all cases. The rare expression of desmin or cytokeratin in HPC suggests either the occurrence of divergent differentiation or, less likely, the possibility that its distinctive morphology is but a phenotype shared by several types of meningeal sarcoma.

Adult↗

Subcutaneous panniculitis-like T-cell lymphoma: clinicopathologic, immunophenotypic, and genotypic analysis of alpha/beta and gamma/delta subtypes.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon cutaneous lymphoma that has been proposed as a distinct clinicopathologic entity, but studies of SPTCL are limited. We studied the clinicopathologic, immunophenotypic, and genetic features of 11 SPTCLs. All cases had a variable admixture of pleomorphic small, medium, or large lymphocytes and histiocytes infiltrating the subcutis in a lobular panniculitis-like pattern. A granulomatous reaction was seen in three cases and erythrophagocytosis in four. Karyorrhexis and fat necrosis were present in all cases. Angioinvasion was seen in seven SPTCLs; four had areas of coagulation necrosis. All cases expressed T-cell-associated antigens (CD3epsilon, CD45RO, or CD43) and T-cell receptors (TCR); nine expressed alphabeta TCRs and two expressed gammadelta TCRs. T-cell receptor-gamma, TCRbeta, or TCRdelta genes were clonally rearranged in 8 of 10 cases studied. Both gammadelta SPTCLs expressed Vdelta2+ TCRs and were CD4-, CD8- and CD56+. CD56 was negative in seven of nine alphabeta SPTCLs and inconclusive in the other two. Six of nine alphabeta SPTCLs were CD8+; the CD4/CD8 phenotypes were indeterminate in the other three. Cytolytic granule-associated proteins were expressed by all SPTCLs (11 of 11 were TIA-1+, 4 of 4 were perforin+). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER-1) was negative in all cases. Most patients responded to systemic chemotherapy or local radiation therapy. Seven patients are alive: four without disease (19-73 months) and three with disease (32-72 months); four died: three of disease (3-25 months) and one without disease (42 months). We conclude that SPTCLs are clonal, EBV-, cytotoxic T-cell lymphomas derived from alphabeta T-cells or gammadelta T-cells. The gammadelta SPTCLs appear to be preferentially derived from the Vdelta2+ subset. Subcutaneous panniculitis-like T-cell lymphoma may be rapidly fatal or indolent; local therapy may be appropriate for some patients.

Adolescent↗

Paraffin section immunophenotype of cutaneous and extracutaneous mast cell disease: comparison to other hematopoietic neoplasms.

Mast cell disease (MCD) is a rare proliferation that may be easily confused with other hematopoietic tumors. Several paraffin section antibodies immunoreact with mast cells but most are not specific. Tryptase, a specific marker of mast cells, may not be cost-effective to maintain in a laboratory because of the rarity of these lesions. This study was undertaken to assess the immunoreactivity of MCD and attempt to select a limited antibody panel for diagnosing MCD among hematopoietic tumors that morphologically mimic MCD. Immunophenotyping of cutaneous ( 10 cases) and extracutaneous (18 cases) MCD, as well as 94 other hematopoietic neoplasms, was performed on paraffin sections. All cases of MCD showed strong and diffuse positivity for CD68 and tryptase. In the vast majority of the cases, the mast cells were also positive for CD117 (27 of 28) and CD43 (25 of 27). Four cases (40%) of cutaneous MCD demonstrated a subpopulation of mast cells expressing myeloperoxidase (MPX), whereas all extracutaneous MCD were negative for MPX. Two (40%) extramedullary myeloid tumors (EMT) expressed CD43, CD68, CD 117, and MPX, but none expressed tryptase. CD43, CD68, CD117, and tryptase were expressed by 25%, 1%, 15%, and 1%, respectively, of all B-cell lymphoid neoplasms, and none expressed more than one of these four antigens. We conclude that (1) cutaneous MCDs may demonstrate a subpopulation of MPX antigen expressing tumor cells and may be confused with cutaneous involvement by myeloid leukemia if other antibodies are not used; (2) tryptase is the most specific mast cell marker among the antibodies studied; and, (3) the detection of tryptase, together with CD68, CD117, and usually CD43, is unique to MCD among hematopoietic tumors.

Adult↗

Metanephric adenoma, nephrogenic rests, and Wilms' tumor: a histologic and immunophenotypic comparison.

Metanephric adenoma (MA) is a renal tumor that is generally detected in adults and occasionally in children. These tumors usually behave in a benign fashion. Although the histogenesis of MA is unclear, a morphologic similarity to Wilms' tumor (WT) complex exists. Six cases of MA, five cases of childhood WT (CWT), two cases of adult WT (AWT), and four cases of treated MWT and/or nephrogenic rests (MWT/NR), with paraffin blocks available for use, were retrieved from the surgical pathology files of the Mayo Clinic. Clinical information was extracted from the medical record. Immunoperoxidase stains for WT1, AE1, CK7, CD57, CD56, and desmin were performed on paraffin sections from all cases. All six cases of MA were strongly and diffusely positive with antibodies to WT1 and CD57 and focally positive with antibodies to CK7. Three cases showed focal faint staining in <5% of the cells with keratin AE1. Stains for CD56 and desmin were negative. All seven cases of WT, including five CWT and two AWT, were strongly and diffusely positive with WT1 in the blastema and epithelium but showed only weak focal positivity in stromal cells. Six cases were diffusely positive for CD56 and one case showed focal positivity. Keratin AE1 was positive in one case of AWT and focally positive in the other AWT. The blastema of all cases of WT were negative for desmin, CK7, and CD57, although staining for keratin AE1, CD56, and CD57 was seen in maturing tubules of CWT cases. Of the five CWT cases, two had associated NR and two showed maturing WT after treatment. The areas of NR and maturing WT were histologically similar to MA and were composed of small tubules with uniform nuclei with no mitotic activity, scant cytoplasm, and focal calcifications. All four cases of maturing WT/NR were positive for WT1 and focally positive for CD57, CK7, and AE1. Stains for CD56 and desmin were negative except in foci of residual blastema, which stained for CD56 but lacked CD57 and CK7 staining. Five cases each of renal cell carcinoma, papillary renal cell carcinoma, and oncocytoma were negative for WT1. Two of five cases of chromophobe carcinoma showed very weak staining present in <10% of tumor nuclei. Metanephric adenoma is histogenetically related to WT and is morphologically and immunophenotypically identical to maturing WT and nephrogenic rests.

Adenoma↗

Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients.

Adrenal cortical neoplasms in pediatric patients (<20 years) are rare. The clinical manifestations and biologic behavior of these lesions can be quite distinct from their histologically similar counterparts in the adult population, making pathologic criteria for distinguishing benign from malignant tumors equivocal. We undertook a study of 83 adrenal cortical neoplasms to determine if adult clinical and histologic features can be applied to pediatric patients in an outcome-based analysis. Most of the patients (50 girls and 33 boys) presented with hormone-related symptoms present for a mean of 6.8 months. The tumors ranged in size from 2 to 20 cm (mean 8.8 cm). Histologic parameters examined included capsular and/or vascular invasion, extraadrenal soft tissue extension, growth pattern, cellularity, necrosis, cytoplasmic eosinophilia, nuclear pleomorphism, nuclear-to-cytoplasmic ratio, prominent nucleoli, mitotic figures, atypical mitotic figures, bands of fibrosis, and calcifications. Immunophenotypically, there was reactivity with inhibin, vimentin, CK5, and focally with p53 and Ki-67. All patients underwent adrenalectomy, and 20 patients received adjuvant therapy. All patients with tumors classified as adenomas (n = 9) were alive, without evidence of disease (mean 14.7 years), whereas 21 patients with carcinomas had died with disease (mean 2.4 years). Only 31% of histologically malignant tumors behaved in a clinically malignant fashion. Features associated with an increased probability of a malignant clinical behavior included tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension into periadrenal soft tissue, confluent necrosis, severe nuclear atypia, >15 mitotic figures/20 high power fields, and the presence of atypical mitotic figures. Vena cava invasion, necrosis, and increased mitotic activity (>15 mitotic figures/20 high power fields) independently suggest malignant clinical behavior in multivariate analysis.

Adenoma↗

Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis.

Occasionally, primary large B-cell lymphomas (LBLs) arising in the spleen present with a micronodular pattern involving the splenic white pulp but sparing the red pulp. Histologically, the nodules contain scattered large B cells in a background of numerous T cells and histiocytes. They can cause substantial difficulty in histologic diagnosis as the morphology can mimic reactive and inflammatory lesions as well as other lymphoid neoplasms. In this study, we examined the histology and immunophenotype of the micronodular T-cell/histiocyte-rich LBL (MTLBL) of the spleen with a view to establish the characteristics that may be helpful in diagnosis. Paraffin-embedded material from 17 cases of MTLBL was studied. Clinical features and histology were reviewed and immunohistochemistry was performed for immunoglobulins, CD20, CD79a, CD3, CD68, CD10, BCL6, BCL2, OCT-2, epithelial membrane antigen, CD30, CD138, and EBV markers. The median age of presentation was 56 years, and the most frequent presenting features were anemia and B symptoms. All cases showed a micronodular pattern of involvement. The tumor nodules comprised a mixture of numerous CD3+ T cells and CD68+ histiocytes and scattered large CD20+ B cells with immunoglobulin light chain restriction. They were positive for BCL6 and OCT2 but negative for CD10, CD138, and EBV markers. There was variable expression of epithelial membrane antigen, Bcl-2, and CD30. No follicle dendritic cell meshwork infrastructure underlying the nodules could be demonstrated by staining for CD21 or CD35 antigens. The prognosis was poor; seven of the 12 cases with follow-up were dead within 2 years. MTLBL is unique variant of T-cell/histiocyte-rich diffuse LBL, characterized by primary splenic presentation and a micronodular architecture. The main differential diagnoses include granulomatous inflammation, Hodgkin's lymphoma, follicular lymphoma, and peripheral T-cell lymphomas.

Adult↗

Air pollution and distributions of lymphocyte immunophenotypes in cord and maternal blood at delivery.

A cross-sectional study of deliveries in two districts in the Czech Republic, 1994-1996, assessed the relation between air pollution and lymphocyte immunophenotype distributions. Maternal and cord blood samples were assayed by flow cytometry within 24 hours of delivery for 303 deliveries from Teplice, a polluted district, and 215 from Prachatice, a less polluted district. Analyses focused on: CD3(+) T-lymphocytes, CD3(-) CD19(+) B-lymphocytes, and CD3(-) CD16(+)56(+) natural killer (NK) lymphocytes, as well as the subsets CD3(+)CD4(+) ("T-helper") and CD3(+)CD8(+) ("T cytotoxic/suppressor") and the ratio of these two lymphocytes. We collected reproductive, occupational, and life-style information by questionnaire, and abstracted data on labor and delivery from medical records. After adjustment for numerous risk factors in multivariate linear regression models fit for each lymphocyte subset, mothers from Teplice had lower percentages of total T-cells and of CD4(+) cells, and a lower ratio of CD4(+):CD8(+) cells. Cord bloods from Teplice had a higher percentage of NK cells and a less precise lower percentage of T-cells. Stronger differences in maternal lymphocytes were seen when analyses were limited to the central hospital in each district. Heavy air pollution may affect the immune system in pregnant women and/or fetuses, reflecting an acute and/or chronic effect, although unmeasured confounders could also play a role.

Air Pollution↗

Responsiveness to interferon treatment of human melanoma cells correlates to immunophenotype.

Clinical trials with interferon (INF) treatment in patients with advanced metastatic melanoma have met with limited success, suggesting that only a small subgroup of patients with melanoma is sensitive to INF therapy. For therapeutic strategies, it would be of great value to discriminate and define markers related to the anti-proliferative effects of INF. In the present study, we report on the in vitro growth inhibitory effects of INF in six human melanoma cell lines; this is associated with a modulation of cell surface markers. The responsiveness of human melanoma cell lines in vitro to INF-alpha shows a good correlation with a specific immunophenotype (TA99-/EGF-R+ or HLA-DR+). No marker correlated with sensitivity or resistance to INF-beta or INF-gamma. This is the first report identifying cell surface markers of human melanoma cells which might have a predictive value for the clinical response to INF-alpha.

Antibodies, Monoclonal↗

Morphologic, immunophenotypic, and molecular evaluation of bone marrow involvement in non-Hodgkin's lymphoma.

The diagnosis of marrow involvement in non-Hodgkin's lymphoma (NHL) relies on morphology with support from immunophenotyping by flow cytometry (FCM). We assessed the relative sensitivity of morphology, FCM, and consensus primer polymerase chain reaction (PCR) of antigen receptor genes in the detection of marrow involvement. In 78 of 100 (78%) cases, there was concordance between FCM and PCR. FCM detected more cases of clonality in B-cell neoplasia. There were 40 cases with objective evidence of involvement by B-cell neoplasia. In this group, FCM had a sensitivity of 97.5% (39 of 40); PCR had a sensitivity of 67.5% (27 of 40). In contrast, PCR had a sensitivity of 71.4%, and FCM a sensitivity of 28.6%, in T-cell neoplasia. In all 12 cases with involvement detected by biopsy, there was objective evidence of clonality. However, clonality was detected in four of seven patients with chronic lymphocytic leukemia and in five of eight patients with T-cell neoplasia in the absence of morphologically detectable disease. Clonality was identified in only one of seven patients with B-cell lymphoma in which the biopsy was interpreted as "suspicious but not diagnostic of involvement." We conclude that morphology remains of central importance in the evaluation of marrow involvement in NHL. We show that FCM and PCR identify involvement in the absence of morphologically apparent disease. In B-cell neoplasms, FCM remains the method of choice for the detection of clonality. PCR for T-cell receptor gene rearrangements may be an important adjunct to the diagnosis of marrow involvement in patients with T-cell neoplasms.

Antigens, CD↗

Viral load and immunophenotype of cells obtained from lymph nodes by fine needle aspiration as compared with peripheral blood cells in HIV-infected patients.

We wished to establish the feasibility of fine needle aspiration of lymph nodes as a noninvasive method for measuring subsets of immune cells and viral load in HIV-infected patients. Twenty-five patients (CD4+ T cell range 4-760/microl, median 362) were selected. Lymph node aspiration was attempted in 21 patients. Lymph node cells (LNC), ranging from 6 x 10(3) to 2 x 10(6) (median 6 x 10(5)) were obtained in 17 subjects, and compared with peripheral blood mononuclear cells (PBMC) obtained simultaneously. Immunophenotype could be determined by flow cytometry in 9 patients. Mean percent of CD4+ CD3+ T cells in LNC and PBMC and 23.2 and 14.6. Mean percent of CD8+ CD3+ T cells in LNC and PBMC was 23.1 and 45.0, respectively. Therefore, CD4+/CD8+ ratios were much higher in LNC (mean +/- SD: 1.06 +/- 0.31) than in PBMC (0.35 +/- 0.13). The amount of HIV DNA (11 patients) and RNA (8 patients) was determined in the plasma, LNC, and PBMC by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). The number of copies of viral DNA/10(5) cells was higher in LNC than in PBMC (LNC/PBMC ratio ranger: 0.54-25, median 3.4). The number of copies of unspliced viral RNA/10(5) cells was much higher in LNC than in PBMC (LNC/PBMC ratio range 65-1,159, median 435). The plasma RNA copy number, a measure of circulating cell-free virus, was correlated with the RNA copy number in PBMC, but not in LNC. A RT-PCR system specific for spliced transcripts was also used to assess the level of transcripts independent of genomic RNA. This assay also detected more signal in LNC than in PBMC. The level of spliced transcripts in LNC and PBMC correlated with the amount of full-length RNA detected by competitive PCR. A semiquantitative coculture assay with lymphoblasts from healthy donors was used to assess the infectivity of LNC as compared with PBMC in 14 patients. The minimum number of LNC necessary to cause a positive coculture ranged from 10(3) to > 10(5) (median 10(4)); the corresponding number for PBMC ranged from 10(3) to > 10(6) (median 5 x 10(5)). In most patients selected for palpable lymph nodes, LNC could be obtained by fine needle aspiration, thus allowing noninvasive monitoring of viral burden in lymphoid tissue. The present study also suggests that both T-cell subsets and viral load differ in the blood and lymphoid tissue, which raises the question of whether the study of the lymphoid tissue would yield better prognostic markers of disease course.

Adult↗

Immunophenotype of blood lymphocytes in neuroblastoma-associated opsoclonus-myoclonus.

OBJECTIVE: To determine whether the distribution of peripheral blood mononuclear cells (PBMCs) is altered in paraneoplastic opsoclonus-myoclonus (POM). METHODS: PBMCs from 17 children with POM, 17 children with OM but no tumor, and 17 controls were immunophenotyped using a comprehensive panel of surface markers by dual-laser flow cytometry. All groups were matched for age and gender; POM and OM patients were matched for treatment. RESULTS: In the POM patients, the CD4+ T-cell subset was smaller in both relative size (-18%, P = 0.02) and absolute size (-41%, P = 0.03) compared with controls. The CD4/CD8 ratio also was less (-29% to -44%) and was related to POM duration (P = 0.03). The absolute but not relative size of the gammadelta T-cell subset was reduced (-44%, P = 0.02). There were no significant abnormalities of CD19+ B-cells, CD3- or CD3+ NK cells, HLA-DR+ or CD25+ T-cells, or CD45RA+ or CD45RO+ T-cells. Prior tumor chemotherapy, which was associated with a higher percentage but not number of CD8+ T-cells, did not restore the CD4+ T-cell subset. When the POM and OM groups, which were not significantly different, were combined, chemotherapy decreased both the relative and absolute size of the CD19+ B-cell pool and had small effects on other lymphocyte subsets. CONCLUSIONS: POM is characterized by T-cell abnormalities of PBMCs, the most robust of which is reduction of the CD4+ T-cell subset and the CD4/CD8 ratio. Although this reduction was found previously in cerebrospinal fluid in POM patients, PBMC subsets did not otherwise reflect cerebrospinal fluid abnormalities. Longitudinal studies will be necessary to determine whether PBMC abnormalities could serve as treatment markers.

Antineoplastic Agents↗

Primary malignant melanoma of the oesophagus: a clinical and pathological study with emphasis on the immunophenotype of the tumours for melanocyte differentiation markers and cancer/testis antigens.

SUMMARY: Primary malignant melanomas of the oesophageal squamous mucosa are exceedingly rare. We present here the clinical and pathological findings of 10 patients (mean age 64 years) with primary oesophageal melanoma, with emphasis on the immunophenotype of the tumours. The majority of melanomas were located in the mid to distal oesophagus and were large (mean tumour size at the time of diagnosis 6.2 cm; mean depth of invasion 1.86 cm). All but two of the melanomas were associated with an extensive in situ component. Half of the tumours were amelanotic. The histological spectrum was wide, including appearances mimicking lymphoma, poorly differentiated adenocarcinoma or sarcoma. Immunohistochemical studies were performed on six tumours using monoclonal antibodies (MAb) to S100 protein, tyrosinase (MAb T311), Melan-A (MAb A103), and gp100 (MAb HMB-45), as well as antibodies to five cancer/testis (CT) antigens (MAb CT7-33 to CT7/MAGE-C1, MAb ESO121 to NY-ESO-1, MAb 57B to MAGE-A4, MAb MA454 to MAGE-A1, and MAb M3H67 to MAGE-A3). Seven patients had metastatic disease at the time of presentation. All but one patient underwent resection of the tumour with negative surgical margins. Survival was poor, with a mean survival of 19.8 months. One patient, however, whose tumour was limited to the submucosa, is still alive 108 months post-oesophagectomy. All six melanomas examined by immunohistochemistry were positive for all the melanocyte differentiation markers tested. In addition, they were all positive for CT antigens, with MA454 being the most commonly found, suggesting that CT antigens may be a promising immunotherapeutic target for oesophageal melanomas.

Adult↗

Immunohistochemical expression of p63 in endometrial polyps: evidence that a basal cell immunophenotype is maintained.

OBJECTIVE: Although endometrial polyps likely originate from reserve cells in the basal layer, the underlying biology is not fully understood. One protein that plays an important role in regulating epithelial proliferation and differentiation is the 63-kd membrane protein (p63), which is also a marker of basal and reserve cells in the female genital tract. Our objective was to determine whether p63 is expressed differently in postmenopausal endometrial polyps than in the adjacent endometrium. DESIGN: In this study, 36 specimens of endometrial polyps and 36 samples of the adjacent endometrium were obtained from postmenopausal women through hysteroscopic surgery performed in a tertiary-care university hospital. Immunohistochemistry was used to evaluate the expression of p63 in all samples. RESULTS: The majority of endometrial polyp samples (94.4%) presented nuclear immunostaining for p63, whereas only 5.6% of adjacent endometrium samples were positive for p63 (P < 0.0001). Distribution of p63 immunostaining in the endometrial polyp samples was homogeneous. CONCLUSIONS: Our results provide evidence that a basal cell immunophenotype is maintained in the endometrial polyps seen in postmenopausal women, suggesting that p63 plays a role in the pathogenesis of such polyps.

Aged↗

Occurrence of t(8;22)(q24.1;q11.2) involving the MYC locus in a case of pediatric acute lymphoblastic leukemia with a precursor B cell immunophenotype.

The authors describe a child with clinical presentation of acute leukemia and an immunophenotype consistent with precursor B-cell acute lymphoblastic leukemia. However, the lymphoblasts had atypical L3 features and the chromosome rearrangement t(8;22)(q24.1;q11.2) involving the MYC locus. The cytogenetic features in this patient were characteristic of mature B/Burkitt leukemia and led to modulation of therapy. This case highlights the need for timely cytogenetic and molecular studies in the diagnosis of acute leukemia.

B-Lymphocytes↗

Immunophenotypes, apoptosis, and expression of Fas and Bcl-2 from peripheral blood lymphocytes in patients with secondary early syphilis.

OBJECTIVES: Whether syphilis influences lymphocyte apoptosis has not been reported so far. GOAL: The goals of this study were to determine whether syphilis influences lymphocyte apoptosis and to investigate the molecular mechanism of apoptosis. STUDY DESIGN: Peripheral blood lymphocyte (PBL) immunophenotypes, apoptosis, and expression of Fas (CD95) and Bcl-2 were detected by flow cytometry in 33 patients with secondary early syphilis and 30 healthy subjects. RESULTS: Compared with the control subjects, the percentage of CD4 T cells and the ratio of CD4:CD8 were significantly decreased, and that of CD8 T cells and the apoptotic rates of PBLs and CD4 T cells were obviously increased in syphilitic patients. Fas overexpression and Bcl-2 downexpression in the syphilitic group were observed in PBLs and CD4 cells but not in CD8 and CD19 cells. CONCLUSIONS: The increased apoptosis of PBLs and CD4 T cells by Fas-mediated death pathway and downexpression of Bcl-2 protein could account for immune dysfunction in secondary early syphilis, which is responsible for the incomplete clearance of Treponema pallidum from the lesions and the chronic infection.

Adolescent↗

Immunophenotypic changes and clinical outcome in B-cell lymphomas treated with rituximab.

Rituximab is a chimeric monoclonal antibody that recognizes the CD20 antigen and is used to treat B-cell non-Hodgkin lymphoma (B-NHL). Few studies have been published examining the use of antibody panels to evaluate B-NHL treated with rituximab. The authors performed a retrospective analysis of immunophenotypic changes and clinical outcome in 18 patients with B-NHL following rituximab therapy. The intensity of CD20 expression was evaluated by flow cytometry and/or immunohistochemistry, before and after rituximab therapy; the latter samples were taken 5 to 12 months after initiating rituximab therapy (median 7 months). Nine of the 18 patients (50%) achieved complete or partial clinical remission and did not have morphologic evidence of lymphoma in the post-therapy samples. The other nine patients (50%) had persistent disease. Two patterns of CD20 expression were noted in the post-therapy samples: unchanged expression of CD20 in neoplastic cells (4/9 cases) and loss of or a significant decrease in detected CD20 expression in neoplastic cells (5/9 cases). These results show that in many cases of B-NHL persisting after rituximab therapy, CD20 expression decreases or is lost, raising the possibility of deletion or expression modulation of the CD20 gene in neoplastic cells. This study also underscores the importance of using a panel of antibodies to evaluate rituximab-treated B-NHL.

Adult↗