Null Cell Type Research Articles

Expression of kisspeptin and KISS1 receptor in pituitary neuroendocrine tumours - an immunohistochemical study.

Pituitary neuroendocrine tumours (PitNETs), traditionally designated as pituitary adenomas, show elatively frequent invasive growth with exceptional metastatic potential, the causes of which are not entirely elucidated. Kisspeptins, which perform their activity through KISS1 receptor (KISS1R), are recognised as metastatic suppressors in many malignant tumours. This study aimed to investigate the immunohistochemical expression of kisspeptin and KISS1R in different types of PitNETs and to compare it with the expression in the normal anterior pituitary, using tissue microarray. The experimental group consisted of 101 patients with PitNETs, with 45 (37.3%) being of gonadotroph, 40 (33.9%) somatotroph, 4 (3.4%) corticotroph, 4 (3.4%) thyrotroph, 3 (2.5%) lactotroph, and 6 (5.1%) null-cell type. The control group consisted of anterior pituitary tissue accidentally removed during the surgery for PitNETs in 17 patients. Kisspeptin expression was observed in both experimental and control groups, without statistically significant differences in the staining intensity. Negative kisspeptin staining was detected in 10 (9.9%), weak in 79 (78.2%), and moderate in 12 tumours (11.9%); none of the tumours had strong staining intensity. The weak staining intensity was predominant in all PitNET types except thyrotroph tumours. Significant statistical difference in terms of kisspeptin expression between types of PitNET and the control group was not observed. Immunohistochemical expression of KISS1R was not observed in the control group or in the experimental group. We conclude that immunohistochemistry, as a method, cannot confirm the involvement of kisspeptin in tumourigenesis and aggressiveness of PitNETs, but potentially supports its antimetastatic role. The absence of KISS1R immunohistochemical expression in all anterior pituitaries and PitNETs in our cohort needs verification through the use of different procedures designed for the detection of the presence and localisation of proteins in the cell.

Non-functional recurrent pituitary adenoma with intracranial metastasis–Pituitary carcinoma: A case report and review of the literature

IntroductionPituitary carcinomas are rare, with only a few case reports to date. We present a null cell type non-functioning pituitary carcinoma (NFPC) with intracranial metastases and a review of the literature. Case reportA 56-year-old male with a history of an aggressive pituitary adenoma was admitted. Initial MRI highlighted a large intracranial mass with leptomeningeal involvement, simulating meningioma. Based on his previous pathology report of the sellar mass, a diagnosis of null cell type non-functioning pituitary carcinoma has been made. ConclusionsAn aggressive recurrent pituitary tumor with suprasellar and/or cavernous sinus invasion is the main characteristics of the NFPC. Single or multiple enhancing dural-based mass(es) mimicking meningioma is the most common MRI finding. The proof of malignancy is the same histopathological features of the recurrent aggressive pituitary tumor in the metastases. The histology alone is not distinctive in terms of malignancy. Most patients require a combined surgery, radiotherapy and chemotherapy.

Immunohistochemical Characterization of Canine Lymphomas

Lymphomas occur by clonal expansion of lymphoid cells and have distinctive morphological and immunophenotypic features. Determination of canine lymphoma immunophenotype is useful for accurate prognosis and further therapy. In the suggested study, we performed an immunohistochemical evaluation of some cases with canine lymphoma diagnosed in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania), in order to characterize them. The investigation included 39 dogs diagnosed with different anatomical forms of lymphoma, following necropsy analysis or assessment of biopsies. The diagnosis of lymphoma was confirmed by necropsy and histopathology (Hematoxylin-eosin stain) examinations. The collected specimens were analyzed by immunohistochemistry technique (automatic method) using the following antibodies: CD3, CD20, CD21 and CD79a. The analyzed neoplasms were characterized as follows: about 64.10% of cases were diagnosed as B-cell lymphomas, 33.34% of cases as T-cell lymphomas, whereas 2.56% of cases were null cell type lymphomas (neither B nor T). Most of multicentric (80%), mediastinal (60%) and primary central nervous system lymphomas (100%) had B immunophenotype, while the majority of cutaneous (80%) and digestive (100%) lymphomas had T immunophenotype. Immunohistochemical description of canine lymphomas can deliver some major details concerning their behavior and malignancy. Additionally, vital prognosis and efficacy of some therapeutic protocols are relying on the immunohistochemical features of canine lymphoma.

A novel "total pituitary hormone index" as an indicator of postoperative pituitary function in patients undergoing resection of pituitary adenomas.

The purpose of this study was to investigate the differences between pre- and postoperative pituitary hormone levels in patients undergoing surgical resection of pituitary adenoma and to identify factors associated with preoperative hypopituitarism.Data from 81 patients with histologically confirmed functioning and non-functioning pituitary adenomas (NFPA) who underwent transsphenoidal resection from January 2011 to December 2013 were retrospectively analyzed. Logistic regression was applied to analyze factors associated with preoperative hypopituitarism. In patients with functioning pituitary adenomas, GH and PRL levels declined after the operation; TSH, FSH and LH levels returned to preoperative values after an initial decline at postoperative day 1. In contrast, with the exception of a postoperative reduction in PRL level, NFPA patients had postoperative ACTH, TSH, FSH and LH levels at 4 months follow-up that were similar to preoperative levels. Similarly, a decrease in total hormone index was observed following surgery irrespective of NFPA type and in null-cell type NFPA patients with values increasing over the 4-month follow-up period. A higher percentage of patients receiving partial resection had high PRL levels (≥200 ng/ mL) compared to those receiving complete resection. Age (P = 0.041) and male sex (P = 0.004) were significantly associated with preoperative hypopituitarism. In conclusion, the postoperative total hormone index decreased immediately following surgery in all patients with pituitary adenoma who underwent resection, and then increased over the follow-up period. The extent of surgical resection correlated with PRL levels >200 ng/mL. Age and male sex were also independent risk factors for preoperative hypopituitarism.

Primary anaplastic large cell lymphoma of trachea with subcutaneous emphysema and progressive dyspnea

Primary anaplastic large cell lymphoma of the trachea is a rare tumor. Common complaints are dyspnea and cough that could mimic a partially refractory asthma in some cases. We report a 16-year-old female with an anaplastic large cell lymphoma (null cell type) in which tracheal involvement was presented with life-threatening airway obstruction and subcutaneous emphysema. After debulking the tumor by endobronchial curettage, the patient was treated with chemotherapy followed by local radiotherapy. She had no evidence of local or distant recurrence after 25 months. Primary anaplastic large cell lymphoma of the trachea is a rare life-threatening disease. Nevertheless, this condition has a good prognosis if diagnosed immediately and treated with chemotherapy and radiotherapy.

Null-Type Anaplastic Lymphoma Kinase–Negative Anaplastic Large Cell Lymphoma Arising in a Silicone Breast Implant Capsule

Null-Type Anaplastic Lymphoma Kinase–Negative Anaplastic Large Cell Lymphoma Arising in a Silicone Breast Implant Capsule

Anaplastic Large Cell Lymphoma: Case Report and Literature Review

This report presents a case of anaplastic large cell lymphoma (ALCL; null cell type) in a Nigerian. ALCL is a well-characterized disorder, but very rare, and arriving at a definitive diagnosis presented a challenge. The use of immunophenotyping and cytogenetic characterization helped resolve the diagnostic confusion. However, it was too late to help the patient once the confusion had been eliminated. This case reflects the peculiar diagnostic challenges and limitations in a resource-scarce environment typical of most rural and semiurban communities in sub-Saharan Africa.

Prognostic Significance of T-Cell or Cytotoxic Molecules Phenotype in Classical Hodgkin’s Lymphoma: A Clinicopathologic Study

Classical Hodgkin's lymphoma (CHL) is characterized by Hodgkin's and Reed-Sternberg (H-RS) cells, most of which are derived from germinal-center B cells. Nevertheless, one or more markers for T cells and follicular dendritic cells (FDC) may be expressed in a minority of H-RS cells in some CHL patients, although the clinical significance of this remains controversial. The aim of this study was to clarify the association between phenotypic expression and clinical outcome in CHL. Participants were 324 consecutive CHL patients, comprising 132 patients with nodular sclerosis (NS), 35 patients with NS grade 2 (NS2), and 157 patients with mixed cellularity (MC). We evaluated the presenting features and prognosis of patients on categorization into four phenotypically defined groups: B-cell (CD20+ and/or CD79a+; n = 63), T-cell and/or cytotoxic molecules (CD3+, CD4+, CD8+, CD45RO+, TIA-1+, and/or granzyme B+; n = 27), FDC (CD21+ without B-cell marker; n = 22), and null-cell types (n = 212). Other potential prognostic factors were examined. The T-cell and/or cytotoxic molecules group showed a significantly poorer prognosis than the other three groups (P < .0001). This finding was seen consistently in multivariate analyses. Morphologic subtyping (NS/NS2/MC) and Epstein-Barr virus positivity were not identified as independent prognostic factors. The presence of T-cell and/or cytotoxic antigens in H-RS cells may represent a poor prognostic factor in CHL, even if their expression is not regarded as lineage specific. Examination of T-cell and/or cytotoxic molecules phenotype in CHL patients is recommended as a routine pathologic practice.

Anaplastic Large-Cell Lymphoma, T-/Null-Cell Type

Anaplastic large-cell lymphoma, T-/null-cell type (ALCL), is a rare disease that has only been well characterized for two decades. Despite this, the biology of ALCL is better understood than that of many other more common variants of lymphoma. This review focuses on the pathophysiology, clinical presentation, and therapy of ALCL, including stem cell transplantation. In particular, the text emphasizes how novel prognostic features and the evolving understanding of the biology of this disease will influence treatment selection and drug development.

Hematologic Malignancies With Primary Retroperitoneal Presentation: Clinicopathologic Study of 32 Cases

The retroperitoneum is an uncommon location for primary lymphomatous involvement. Initial presentation of disease in this site (primary retroperitoneal lymphoma) is considered to be rare. Because of the uncommon anatomic location, the diagnosis and subsequent management of these patients tend to be difficult for both pathologists and clinicians. This report describes our experience during a period of 6 years 4 months with patients with hematologic malignancies primarily presenting in the retroperitoneum. A retrospective search of our medical records generated 32 patients who presented initially with abdominal pain or discomfort as their predominant symptom and who were found by imaging studies to have retroperitoneal mass or masses. All the histopathology slides were reviewed and classified based on the World Health Organization classification. There were 13 male and 19 female patients. Tumor types included diffuse large B-cell lymphoma (n = 12); grade 1 follicular lymphoma (n = 4); grade 3 follicular lymphoma (n = 1); B chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 2); multiple myeloma (n = 1); mixed-cellularity Hodgkin lymphoma (n = 1); nodular sclerosis Hodgkin lymphoma (n = 1); aggressive B-cell lymphoma (n = 4); low-grade B-cell lymphoma (n = 4); lymphoblastic lymphoma, null cell type (n = 1); and precursor B-lymphoblastic lymphoma/leukemia (n = 1). More than half of the cases (17/32) were diagnosed on needle biopsy with immunophenotyping. Although open lymph node biopsy is a preferred method for diagnosis, needle biopsy plays a significant role in this setting, and, coupled with other information such as flow cytometry and immunohistochemistry, it is considered a practical and reliable method.

Prevalence and characterization of anaplastic large cell lymphoma and its association with Epstein-Barr virus in Pakistani patients

Anaplastic large cell lymphoma (ALCL), CD30+, is a subtype of T-non-Hodgkin's lymphoma (NHL). Its most common form is a classical systemic type that involves multiple nodal and extranodal sites. In this study, morphologic, immunohistologic, and genetic studies were performed on ALCL cases in Pakistani patients. The median age of the patients in this study was 45 years (age range: 5–70 years), with a male to female ratio of 3.4:1. Thirty-seven (37) patients were diagnosed to have Ki-1 (CD30+) ALCL, which constituted 2% of all NHLs and 12.6% of all T-NHLs, over a period of 11 years (January 01, 1992–December 31, 2002). The tumors were of either T- or null-cell type with constant (100%) expression of CD30 (Ki-1). The majority of the cases (89.2%) expressed EMA, whereas 40.5% of the cases expressed either CD45 (LCA), CD45RO (UCHL1), or ALK. The mean age of ALCL patients with null-cell phenotype was 33.8 years as compared to those with T-cell phenotype having a mean age of 36.3 years. Out of the 37 cases diagnosed as ALCL, amplifiable DNA was isolated from 28 cases, which were further assessed for T-cell clonality for T-cell receptor (TCR)-β, γ, and immunoglobulin heavy chain (IgH) for the FR2 and FR3 regions. The polymerase chain reaction (PCR) technique demonstrated clonal rearrangement of the TCR β, γ, and IgH regions in 15 (53.6%), 11 (39.3%), and 2 (7.1%) ALCL cases, respectively, out of 28 cases. Association of Epstein-Barr virus (EBV) was noted in seven out of 28 cases (25%) of ALCL by PCR, whereas ISH for EBV-encoded nuclear RNA-1 (EBER-1) detected the presence of EBV in two (16.7%) out of 12 cases, where one was T-cell ALCL and the other null-cell ALCL. Immunostaining for LMP-1 could not be performed, because tissue material was not available. In conclusion, our study demonstrated that the prevalence of ALCL in Pakistan is comparable to that reported for some of the Asian communities and by the International Lymphoma Study Group and that EBV could be partly responsible for the pathogenesis of ALCL.

Detection of a subset of CD30+ anaplastic large cell lymphoma by interphase fluorescence in situ hybridization.

T/null-cell anaplastic large cell lymphoma (ALCL) is a morphologically and clinically heterogeneous group of non-Hodgkin's lymphoma; to date several morphologic variants have been described on histologic specimens. However, the cytologic features of these variants in the fine-needle aspiration (FNA) specimens have not been well evaluated. The t(2;5)(p23;q35) has been identified in a subset of T/null-ALCL and is known to be associated with a favorable prognosis. We reviewed the cytomorphologic characteristics in 24 FNA specimens of ALCL. In all cases, the diagnosis was confirmed on histologic specimens, and immunohistochemical studies for anaplastic lymphoma kinase (ALK) protein expression were performed on the aspirates. The presence of ALK breakpoints were evaluated in nine cases, using a DNA break-apart probe on chromosome 2 covering the ALK gene by fluorescence in situ hybridization (FISH) techniques. Two hundred cells per case were examined. The results were expressed as the percentage of cells containing more than two signals of chromosome 2 to the total number of cells counted. FNA sites included lymph nodes (20), lung (2), breast (1), and soft tissue (1). The median age of the patients was 56 yr (range, 17-75 yr). Twenty cases had systemic involvement; in four cases, skin was the primary site with secondary involvement of the lymph nodes. All cases were CD30(+) by immunohistochemistry; 20 were of T-cell phenotype and 4 were null cell type. The cytologic evaluation revealed typical anaplastic morphology (common type) with many "hallmark cells" in 16 (67%) cases. Other morphologic variants identified were small cell pattern in five cases, monomorphic pattern in two cases, and lymphohistiocytic pattern in one case. FISH studies showed that six (66.7%) of nine cases had at least two signals of chromosome 2, consistent with ALK breakpoints. With careful cytomorphologic evaluation in conjunction with appropriate immunohistochemical studies, a diagnosis of ALCL can be confidently made in the FNA specimens in the cellular aspirates and its morphologic variants also can be recognized. Furthermore, the FNA specimen is suitable in detecting ALK breakpoints by FISH study, permitting rapid identification of a subset of patients with ALCL, who may have a favorable prognosis. Using a commercially available probe, detection of ALK breakpoints in the FNA specimens is simple and can be a useful diagnostic adjunct in cases where distinction from other lymphomas or lymphoid lesions is morphologically difficult.

UVB irradiation reduces the half-life and transactivation potential of the human papillomavirus 16 E2 protein

Human papillomaviruses (HPV) are causative agents of human cancers including those of the cervix and also of the head and neck; HPV16 is the most commonly found type in these diseases. The viral E2 protein regulates transcription from the viral genome by interacting with DNA-binding sequences in the HPV transcriptional control region; it also regulates replication by interacting with and recruiting the HPV replication factor E1 to the viral origin. Therefore, E2 is essential for the viral life cycle. The E2 protein interacts with several proteins involved in the cellular response to DNA damage including p53, TopBP1, and PARP. We therefore set out to establish whether DNA-damaging agents can regulate E2 activity. Here we show that UVB irradiation downregulates transcriptional activity of both HPV16 and HPV8 E2, while hydroxyurea and etoposide do not. This downregulation of E2 activity is independent of p53 function as it occurs in p53 wild type and null cell types as well as in the presence of functional HPV16 E6 that degrades p53. Using stable cell lines expressing E2 we show that this downregulation of E2 function by UVB is due to a reduction of the E2 protein half-life. The identification of the pathway(s) through which UVB downregulates E2 transcriptional activity and protein levels will present a novel target for the treatment of HPV-related diseases.

Anaplastic Large Cell Lymphomas Presented as Bone Lesions: A Clinicopathologic Study of Six Cases and Review of the Literature

Non-Hodgkin's lymphomas uncommonly present as bone lesions. Most of these tumors are diffuse large B-cell lymphomas. Anaplastic large cell lymphoma (ALCL) presented as bone lesions is exceedingly rare. In this study, we describe six cases of ALCL that presented as solitary or multiple bone lesions. The average patient age was 33 years (range, 4 to 63 years) and the male to female ratio was 2:1. Fever and localized bone pain were the most frequent presenting symptoms. Radiologic examinations revealed osteolytic lesions in all cases, with three (50%) being multiple lesions and five (83%) involving the axial bones. All patients were initially assessed to have only bone involvement. Staging studies revealed mild cervical lymphadenopathy in one patient and no evidence of extraskeletal disease in the other five patients. Histologically, there was diffuse infiltration of one or more bones by large pleomorphic lymphoma cells. Immunohistochemical studies showed all six neoplasms were positive for CD30, EMA, and granzyme B. One case was of T-cell lineage, positive for CD3. One case was positive for the T-cell-associated antigen CD4. The remaining four cases were of null-cell type. In-situ hybridization for EBV was performed in five cases; all were negative. Despite the relatively low International Prognostic Index (IPI) of these patients (mean, 1.67; range, 1 to 3), the overall prognosis was relatively poor: three of six died of disease within 2 years of diagnosis, and two of six were alive with evidence of disease (follow-up, 6 mo to 2 years). Thus, compared to their nodal counterparts, ALCLs that present as bone lesions are distinguished by their uniform expression of EMA and granzyme B, and a relatively poor clinical outcome. Our results also suggest that ALK-1 expression in this clinical setting is not a favorable prognostic indicator.

The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists.

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796 cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T-cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T-cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T- and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV-1.

Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas

Despite its clinical and histological heterogeneity, anaplastic large cell lymphoma (ALCL) is now a well-recognized clinicopathological entity accounting for 2% of all adult non-Hodgkin's lymphomas (NHL) and about 13% of pediatric NHL. Immunophenotypically, ALCL are of T cell (predominantly) or Null cell type; by definition, cases expressing B cell antigens are officially not included in this entity. The translocation (2;5)(p23;q35) is a recurring abnormality in ALCL; 46% of the ALCL patients bear this signature translocation. This translocation creates a fusion gene composed of nucleophosmin (NPM) and a novel receptor tyrosine kinase gene, named anaplastic lymphoma kinase (ALK). The NPM-ALK chimeric gene encodes a constitutively activated tyrosine kinase that has been shown to be a potent oncogene. The exact pathogenetic mechanisms leading to lymphomagenesis remain elusive; however, the synopsis of evidence obtained to date provides an outline of likely scenarios. Several t(2;5) variants have been described; in some instances, the breakpoints have been cloned and the genes forming a new fusion gene with ALK have been identified: ATIC-ALK, TFG-ALK and TPM3-ALK. Cloning the translocation breakpoint and identifying the ALK and NPM genes provided tools for screening material from patients with ALCL using various approaches at the chromosome, DNA, RNA, or protein level: positive signals in the reverse transcriptase-polymerase chain reaction (RT-PCR) and the immunostaining with anti-ALK monoclonal antibodies (McAb) serve as the most convenient tests for detection of the t(2;5) NPM-ALK since the fusion gene and ALK protein expression do not occur in normal or reactive lymphoid tissue. The wide range of NPM-ALK positivity reported in different series appears to be dependent on the inclusion and selection criteria of the ALCL cases studied. Overall, however, 43% of ALCL cases were NPM-ALK+ (83% of pediatric ALCL vs 31% of adult ALCL). Occasional non-ALCL B cell lymphomas (4%) with diffuse large cell and immunoblastic histology and Hodgkin's disease cases (3%) were NPM-ALK-, but these data are questionable. The aggregate results indicate that, in contrast to primary nodal (systemic) ALCL, the t(2;5) may be present in only 10-20% of primary cutaneous ALCL and rarely, if at all, in lymphomatoid papulosis, a potential precursor lesion; however, these 10-20% positive cases were not confirmed by anti-ALK McAb immunostaining and may represent an overestimate. Positivity for NPM-ALK is associated to various degrees with the following parameters: 44% and 45% of ALCL cases with T cell and Null cell immunophenotype, respectively, are positive, whereas only 8% of cases with a B cell immunoprofile are positive; the mean age of positive patients is significantly younger than that of negative patients; positive cases carry a better overall prognosis (but not in all studies). Recently, the homogenous category of ALK lymphoma ('ALKoma') has emerged as a distinct pathological entity within the heterogenous group of ALCL. The fact that patients with ALK lymphomas experience significantly better overall survival than ALK- ALCL demonstrates further that analysis of ALK expression has important prognostic implications. The term ALK lymphoma signifies a switch in the use of the diagnostic criteria: cases are selected on the basis of a genetic abnormality (the ALK rearrangement), instead of the review of morphological or immunophenotypical features which are clearly more prone to disagreement and controversy. Since its initial description in 1985 ALCL has become one of the best characterized lymphoma entities.

上顎洞と背部に発生し，化学療法が奏効した未分化大細胞型リンパ腫の１例

Anaplastic large cell lymphoma (ALCL) was recently recognized as a distinct type of non-Hodgkin's lymphoma characterized by anaplastic, large cells and expression of CD30 on immunohistochemical analysis. Since oral lesions of ALCL are rare, this tumor is not well documented in the literature. We report a case of ALCL of the maxillary sinus and back in a 79-year-old man who had an extensive swelling with an ulcer, extending from the left cheek to the upper gingiva, and a subcutaneous mass of the back. Computed tomography and magnetic resonance imaging of the gingival swelling revealed a bulky tumor in the left maxillary sinus with bone destruction. Histological examinations of both lesions were performed. The lesions were both diagnosed as CD30-positive, null cell type ALCLs. Complete remission was achieved by six courses of CHOP chemotherapy. There have been no signs of recurrence 10 months after treatment; however, long-term follow-up is necessary because of a relatively high rate of recurrence.

Frequent Expression of the B-Cell–Specific Activator Protein in Reed-Sternberg Cells of Classical Hodgkin’s Disease Provides Further Evidence for Its B-Cell Origin

AbstractThe neoplastic cells of classical Hodgkin’s disease (cHD), ie, Hodgkin and Reed-Sternberg cells (HRS cells), contain clonally rearranged Ig genes, but are dissimilar to normal B cells in that they mostly do not display B-cell antigens such as CD20 or CD19. The transcription factor B-cell–specific activator protein (BSAP) influences numerous B-cell functions such as B-cell antigen expression, Ig expression, and class switch. We analyzed the expression of BSAP in cHD and control tissues by isotopic in situ hybridization and immunohistochemistry to determine whether BSAP is expressed in HRS cells and, if so, whether it may be involved in the genesis of the abnormal phenotype of these cells. Both in normal lymphoid tissue and non-Hodgkin lymphomas, BSAP transcripts and protein were almost exclusively found in B cells and B-cell lymphomas (40 cases), but were absent from the tumor cells of T-cell neoplasms (41 cases), including 19 cases of anaplastic large cell lymphoma of T- and null-cell type. Among cHD, variable numbers of HRS cells exhibited BSAP transcripts (22 of 25 cases) and protein (28 of 31 cases). Our findings show that BSAP is sufficiently specific to serve as B-cell marker. BSAP expression in HRS cells provides further strong evidence for a frequent B-cell origin of cHD and helps distinguish this disease from anaplastic large cell lymphoma of T- and null-cell type. Because BSAP is much more frequently expressed in HRS cells than the conventional B-cell antigens, the abnormal immunophenotype of HRS cells with frequent absence of B-cell antigens does not appear to be due to absent BSAP expression.

Frequent Expression of the B-Cell–Specific Activator Protein in Reed-Sternberg Cells of Classical Hodgkin’s Disease Provides Further Evidence for Its B-Cell Origin

The neoplastic cells of classical Hodgkin’s disease (cHD), ie, Hodgkin and Reed-Sternberg cells (HRS cells), contain clonally rearranged Ig genes, but are dissimilar to normal B cells in that they mostly do not display B-cell antigens such as CD20 or CD19. The transcription factor B-cell–specific activator protein (BSAP) influences numerous B-cell functions such as B-cell antigen expression, Ig expression, and class switch. We analyzed the expression of BSAP in cHD and control tissues by isotopic in situ hybridization and immunohistochemistry to determine whether BSAP is expressed in HRS cells and, if so, whether it may be involved in the genesis of the abnormal phenotype of these cells. Both in normal lymphoid tissue and non-Hodgkin lymphomas, BSAP transcripts and protein were almost exclusively found in B cells and B-cell lymphomas (40 cases), but were absent from the tumor cells of T-cell neoplasms (41 cases), including 19 cases of anaplastic large cell lymphoma of T- and null-cell type. Among cHD, variable numbers of HRS cells exhibited BSAP transcripts (22 of 25 cases) and protein (28 of 31 cases). Our findings show that BSAP is sufficiently specific to serve as B-cell marker. BSAP expression in HRS cells provides further strong evidence for a frequent B-cell origin of cHD and helps distinguish this disease from anaplastic large cell lymphoma of T- and null-cell type. Because BSAP is much more frequently expressed in HRS cells than the conventional B-cell antigens, the abnormal immunophenotype of HRS cells with frequent absence of B-cell antigens does not appear to be due to absent BSAP expression.

Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients.

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).