CD30 expression in non-Hodgkin''s lymphoma

The CD30 antigen has been reported as the immunophenotypic hallmark of a recently described category of non-Hodgkin's lymphoma, termed anaplastic large cell lymphoma. From a series of approximately 500 lymphomas, 17 cases showing typical anaplastic features have been identified. They were strongly labelled by monoclonal antibodies recognizing CD30 (Ki-1 or BerH2). However, 36 other lymphomas, mainly high-grade, of non-anaplastic cytology also expressed CD30, either diffusely or focally, with a staining pattern identical to that seen in anaplastic large cell lymphomas. This clearly suggests that such lymphomas cannot be identified solely on the basis of being high-grade non-Hodgkin's lymphomas showing CD30 positivity. From the present results, the distinction between the anaplastic and non-anaplastic types would be better made with antibodies to epithelial membrane antigen than to CD30. Clinical data, available for 48 of the patients (16 with anaplastic large cell lymphomas and 32 with non-anaplastic) revealed no significant differences with regard to age at presentation, sex or clinical signs. A short-term follow-up study of 25 patients revealed that for the first 2 years after diagnosis there were no significant differences in patient survival between anaplastic large cell lymphoma, other CD30+ high-grade lymphomas and all high-grade non-Hodgkin's lymphomas considered together. These findings, which must be confirmed by larger studies, suggest that in a general lymphoma clinic there is probably little justification for differentiating anaplastic large cell lymphomas or CD30+ lymphomas from other high-grade non-Hodgkin's lymphomas.     

Intravascular large T-cell lymphoma: a case report of CD30-positive and ALK-negative anaplastic type with cytotoxic molecule expression

We reported a case of intravascular T-cell lymphoma (T-IVL) with anaplastic large cell morphology, the hemophagocytic syndrome, and an aggressive clinical course. Phenotypic analysis of the tumor cells revealed CD2+, CD3−, CD4+, CD5−, CD8−, CD30+, CD56−, T-cell receptor alpha/beta−, ALK−, TIA1+, granzyme B+, and perforin+. No association with Epstein–Barr virus was found by in situ hybridization. A review revealed that 25 cases of T-IVL have been reported in the available literature, only two of which were of CD30+ anaplastic large cell or cytotoxic T-cell type. The findings in the present case may highlight the unique clinicopathologic aspects of a subset of CD30-positive T-IVLs with an ALK-negative cytotoxic phenotype.     

CD30阳性的窦性大B细胞淋巴瘤临床病理学分析

目的 探讨CD30阳性的窦性大B细胞淋巴瘤（SLBCL）的临床病理学特征及其与EpsteiBarr(EB)病毒的关系。方法 结合临床特点、形态学及免疫表型分析,并通过聚合酶链反应（PCR）法检测EB病毒BamHIW DNA片段及免疫组织化学法检测潜肽膜蛋白1（LMP1）,对2例CD30阳性的SLBCL进行分析。结果 2例分别为64岁男性及85岁女性,均表现为浅表淋巴结肿大,其中1例10个月后死于肿瘤。镜下,肿瘤都以窦性分布且彼此黏附的生长方式及相对单形的细胞形态为特征。免疫表型分析提示,两者均呈CD45、CD30、CD20或CD79α阳性而不表达上皮膜抗原（EMA）、ALK1及组织细胞或T细胞的标志。未发现2例有EB病毒感染的证据。结论 CD30阳性的SLBCL是一种形态、表型独特的弥漫大B细胞淋巴瘤变异类型,该瘤需与T/裸细胞性间变性大细胞淋巴瘤及其他一些累及淋巴窦为主的淋巴结病变相鉴别,但与EB病毒可能无关。     

Lack of c-kit (CD117) expression in CD30+ lymphomas and lymphomatoid papulosis.

c-Kit receptor (CD117) is expressed by erythroid, megakaryocytic, and myeloid precursors and mature mast cells and has been reported to be expressed in CD30+ lymphomas such as Hodgkin's disease and anaplastic large-cell lymphoma. Imatinib mesylate, a well-established inhibitor of bcr-abl tyrosine kinase, and currently used for the treatment of patients with chronic myeloid leukemia, also inhibits c-kit receptor kinase activity. In view of the possible use of imatinib as experimental therapy for patients with c-kit-positive tumors, we assessed c-kit expression in CD30+ cell lines and lymphomas. The cell lines were assessed using multiple methods (RT-PCR, flow cytometry, and Western blot). c-Kit expression was also immunohistochemically assessed in 168 CD30+ lymphomas including 87 classical Hodgkin's disease, 63 anaplastic large-cell lymphoma, and 15 cutaneous anaplastic large-cell lymphoma. We also studied 18 cases of lymphomatoid papulosis, a CD30+ lesion closely related to cutaneous anaplastic large-cell lymphoma. Neither c-kit mRNA nor protein was detected in any of the cell lines assessed. Furthermore, treatment with imatinib did not inhibit proliferation of cell lines in vitro. Using immunohistochemistry, only one of 183 (0.5%) lesions was positive for c-kit, the positive case being an ALK-negative anaplastic large-cell lymphoma. Our data demonstrate that expression of c-kit receptor is exceedingly rare among CD30+ lymphomas and lymphomatoid papulosis, suggesting that c-kit receptor is unlikely to be an appropriate target for therapeutic options such as imatinib in patients with these tumors.     

Anaplastic large cell lymphoma: another entity in the differential diagnosis of small round blue cell tumors

We saw in consultation a biopsy specimen from a 6-year old girl with anaplastic lymphoma kinase (ALK)–positive anaplastic large cell lymphoma (ALCL). The tumor arose in soft tissue of the neck, and diagnostic tissue was obtained by core needle biopsy. Histologically, the neoplasm was cellular without pattern. Immunohistochemical workup with a large panel of antibodies at another institution showed immunoreactivity for NB84 and neuron specific enolase (dim). Antibodies specific for CD3, CD20, and CD45/LCA were negative; CD30 or ALK were not assessed. Electron microscopy showed cytoplasmic structures thought to be neurosecretory granules. The neoplasm was interpreted initially as a neuroblastoma. At the time of our review, we considered the possibility of ALCL. Immunohistochemical analysis for CD30 showed bright, uniform expression and ALK was positive in a nuclear and cytoplasmic pattern, confirming the diagnosis of ALK+ ALCL. The purpose of this review is to discuss ALK+ ALCL and many of the other entities included under the rubric of small round blue cell tumor, with a focus on tumors that occur in children.     

Primary cutaneous CD30 positive T-cell lymphoproliferative disorders with aberrant expression of PAX5: report of three cases

Accurate diagnosis of lymphoma includes the assessment of lineage-specific markers. Hematopoietic and lymphoid tissues express PAX5 exclusively in pro-B-cell to mature B-cell stages. However, some mature PAX5+ T-cell lymphomas have been reported. We report three cases of primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPDs) with PAX5 expression: one cutaneous anaplastic large cell lymphoma (ALCL) and two cases of lymphomatoid papulosis (LyP). The three patients were 26 years old and female, 75 years old and female, and 65 years old and male. In all cases, Hodgkin's and Reed-Sternberg-like large lymphoid cells were present, positive for CD30, fascin, and PAX5, and negative for CD3, CD4, CD8, CD20, CD45RO, CD56, cytotoxic markers, and Epstein-Barr virus. The ALCL was accompanied by lymphadenopathy; the patient died of progressive disease 5 months after diagnosis. The LyP cases were localized in the skin with spontaneous regression. One case was diagnosed during pregnancy, transformed to ALCL, and ended in death 32 months after diagnosis despite multi-agent chemotherapy. This study is the first to address the clinical significance of PAX5+ primary cutaneous CD30+ T-cell LPDs. These cases were distinct regarding PAX5 expression and a relatively aggressive clinical course versus conventional primary cutaneous CD30+ T-cell LPDs.     

Frequent expression of CD30 antigen in the primary gastric non-B, non-Hodgkin lymphomas

Most primary gastric lymphomas are of B-cell origin. Fourteen cases of primary gastric non-B, non-Hodgkin lymphomas were studied to evaluate their clinicopathological and immunophenotypic findings. The cases were comprised of 11 men and three women, with a median age of 56.5 years. Most patients underwent surgery either with or without chemotherapy, exhibiting a 5 year survival rate of 57.5%. Morphologically, the neoplastic cells showed various histological features, such as anaplastic large cell lymphoma (ALCL) (n = 3), peripheral T-cell lymphoma, unspecified, large (n = 4), medium-sized (n = 2) and mixed cell (n = 5). Two cases displayed a non-B, non-T cell phenotype, whereas the remaining cases displayed a T-cell phenotype. Six cases were CD4+, while two were CD8+. The neoplastic cells were CD30+ in 10 cases. TIA-1 was positive in six cases. In one case, anaplastic large cell lymphoma kinase (ALK) was identified with immunostaining and chromosomal rearrangement of ALK was detected by fluorescence in situ hybridization (FISH). In conclusion, although the mechanism of CD30 expression is unknown, primary gastric non-B, non-Hodgkin lymphomas tend to express CD30. We consider that some of the cases in the present study may be derived from cytotoxic T cells, similar to systemic and cutaneous ALCL, the majority of which exhibit TIA-1.     

CD30 (ki-1) antigen expression in acute infectious mononucleosis

The activation antigen CD30 (Ki-1) which is expressed by the lymphocytes T and B is related to the "nerve growth factor" (NFGR) like the receptor of the "tumor necrosis factor" (TNF) and is expressed in the group of large-cell anaplastic lymphoma (ACLC) and Hodgkin's lymphoma and in non-Hodgkin's lymphoma and within the T cells of infectious Mononucleosis. We describe a case of a 18 year-old who contracted Acute Infectious Mononucleosis showing lateral cervical lympho adenopathy. The histologic examination was suggestive for a large-cell anaplastic lymphoma with the antigen CD30, expressed by severa atypical immunoblasts. The remarkable immunoblastic proliferation with Reed-Sternberg-like cells, in milieu polymorphous inflammatory cells present in the course of Infectious Mononucleosis, can simulate large cell anaplastic lymphoma, as well as Hodgkins disease and non-Hodgkins lymphoma. The diagnosis for Infectious Mononucleosis is usually clinical and serological but in cases of cervical lymphnode biopsy a differential diagnosis must be done with positive lymphoma CD30. The criteria to differentiate histologically the Infectious Mononucleosis with large cell anaplastic lymphoma and non-Hodgkin s lymphoma are discussed. Finally, the relationship between Infectious Mononucleosis and lymphoproliferative disease Epstein-Barr virus related is examined.     

CD8+ lymphomatoid papulosis and its differential diagnosis

We describe 5 cases (4 males, 14-43 years old; 1 female, 61 years old) of primary cutaneous T-cell lymphoproliferative lesions expressing a CD8/granzyme/CD30-positive phenotype. Four cases were compatible with lymphomatoid papulosis (LyP) based on the clinical course, which was recurrent asymptomatic papular nodular lesions over years responding to methotrexate; granulomatous inflammation and lack of other inflammatory cell elements were characteristic. In 1 case, an initial erroneous diagnosis was made of aggressive epidermotropic CD8+ T-cell lymphoma. The fifth case in this series was first interpreted as representing primary cutaneous anaplastic large cell lymphoma but was later recategorized as primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma owing to the extent of extracutaneous dissemination, including testicular involvement and disease progression despite chemotherapeutic intervention. Although all cases of LyP showed sharp cytoplasmic membrane staining with perinuclear Golgi accentuation with CD30, the recategorized case of aggressive epidermotropic CD8 cytotoxic T-cell lymphoma manifested only a weak cytoplasmic staining pattern. CD8 LyP defines a distinctive entity with characteristic light microscopic and phenotypic findings and has a predilection for young males. CD30 expression can occur in other forms of CD8 lymphoproliferative disease unrelated to primary cutaneous anaplastic large cell lymphoma or LyP.     

CD4+CD56+ lineage negative hematopoietic neoplasm: so called blastic NK cell lymphoma

Blastic natural killer (NK) cell lymphoma is a rare neoplasm characterized by blastoid tumor cells expressing CD4 and CD56, with predominant skin involvement. Although this tumor has been regarded as a neoplasm related to NK cell, recent studies suggested that it is derived from plasmacytoid dendritic cells, but not from NK cell. Herein we report 4 cases of CD4+CD56+ lineage marker-blastic NK cell lymphomas with a review of literatures. The patients were 3 men and one woman. Three of them were young (17, 18, and 22 yr old). Three patients had skin lesions, at initial presentation in two patients and during the course of disease in other patient. Histologically, tumors consisted of monotonous medium to large blastoid cells showing no necrosis, angiocentric growth or epidermotrophism. All four tumors were CD4+ and CD56+. Three expressed CD68 antigen. Lineage specific markers for B- and T cell were negative. All tumors did not express myeloperoxidase. T-cell receptor gene rearrangement, EBV, CD13 and CD33 were negative. In one patient, tumor cells arranged in Homer-Wright type pseudorosette and expressed terminal deoxynucleotidyl transferase(TdT). Despite the standard lymphoma chemotherapy, the tumors, except one lost during follow-up, progressed and relapsed. The patients died 8-60 months after diagnosis.     

Diffuse large B cell lymphoma expressing the natural killer cell marker CD56

The expression of the natural killer (NK) cell antigen, CD56, in hematological malignancies is rare. However, there are several reports that some hematological malignancies, such as T/NK cell lymphoma, multiple myeloma (MM) and acute myeloid leukemia (AML), express this molecule. In B cell non-Hodgkin's lymphomas (NHL), however, very limited number of cases have been reported to express CD56 molecule. Although one study has recently described that half of microvillous B cell lymphoma (MVL), an uncommon subset of large cell lymphoma, expressed CD56, there have been no reports about most common type of B-NHL, diffuse large B cell lymphoma (DLBL) other than a mention of weak CD56 expression in one of 83 DLBL. We herein presented the first case of diffuse large B cell lymphoma expressing CD56 clearly. The immunophenotype determined by immunostaining and flow cytometric analysis was CD10+, CD19+, CD20+, CD45RO-, CD3- and CD56+. On immunohistochemical study, neither bcl-2 nor TIA-1 was positive for tumor cell. Monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was detected, and the sequence analysis of the variable region of IgH (VH) suggested that this tumor was derived from antigen selected post germinal center B cell. Conventional combination chemotherapy (CHOP) was administered, and the patient has still been in complete remission for 10 months.     

Primary anaplastic large cell lymphoma of the adrenal gland

Primary adrenal lymphomas are rare. Most reported cases are of B-cell phenotype and follow an aggressive clinical course. We report a case of primary anaplastic large cell, CD30+ adrenal lymphoma developing in a 62-year-old woman. The patient presented with fatigue and vague right upper quadrant pressure. Computed tomography revealed bilateral adrenal masses. A right adrenalectomy was performed. Histologic evaluation showed islands of large atypical cells surrounded by eosinophilic acellular material. The tumor cells stained positive for CD45, CD45RO, CD43, and CD30. Epstein-Barr virus genome was identified in tumor cells using in situ hybridization. The patient was treated with chemotherapy and a 23-month follow-up examination showed no change in the size of the opposite adrenal gland and no other evidence of lymphoma.     

CD56+/CD4+ lymphomas and leukemias are morphologically, immunophenotypically, cytogenetically, and clinically diverse

CD56, a neural adhesion molecule, is a marker of natural killer (NK) lymphocytes as well as a subgroup of CD8+ T cells. Normal lymphocytes with a CD56/CD4 phenotype are scarce. Physiologic increases may occur in patients with immunosuppression, chronic inflammation, and autoimmune disorders. We report 4 cases of lymphomas/leukemias with the unusual CD56/CD4 phenotype. Two were of T-cell and 2 of true NK-cell origin. The T-cell lymphomas had large granular lymphocyte morphologic features and splenomegaly. One patients had a benign course; the other died within months of the leukemia diagnosis. The 2 NK cell lymphomas had blastic morphologic features, initially involved skin, and had a very aggressive clinical course; 1 patient died of acute leukemia, and 1 had recurrence after bone marrow transplantation. Cytogenetic analyses did not show a consistent pattern of abnormalities. The NK lymphoma with acute leukemia had a t(2;5) but was CD30- and anaplastic lymphoma kinase negative. Although CD56+/CD4+ lymphomas/leukemias are a heterogeneous group, there may be a distinct subgroup of NK lymphoblastoid lymphomas of the skin, judging from our cases, as well as those previously reported.     

Immunohistochemical analysis of CD30-positive lymphoproliferative disorders for expression of CD95 and CD95L.

Primary cutaneous (PC) CD30-positive large cell lymphoma and lymphomatoid papulosis (LyP) represent the spectrum of PC CD30-positive lymphoproliferative disorders (LPDs) associated with a favorable prognosis. Noncutaneous CD30-positive anaplastic large cell lymphoma (ALCL), although morphologically similar to PC CD30-positive LPDs, seems to be a biologically distinct entity. Cell lines derived from noncutaneous ALCL express CD95 and undergo CD95-induced apoptosis. Little is known about expression or function of CD95/CD95L in cutaneous lesions. We examined a series of PC CD30-positive LPDs and noncutaneous ALCL for expression of CD95/CD95L to investigate possible differences between these histologically similar but biologically distinct entities. Paraffin-embedded, formalin-fixed tissue sections from 25 cases of CD30-positive LPDs (10 noncutaneous ALCL, 15 PC CD30-positive LPDs) were immunostained for CD3, CD20 (L26), CD43 (Leu22), CD30 (BerH2), anaplastic lymphoma kinase (ALK-1), CD95, and CD95L (C-33). One hundred large atypical cells and 100 small lymphocytes were counted to determine the percentage of CD95/ CD95L-positive cells. Statistical analysis using the Mann-Whitney U test was performed. CD95 expression was slightly higher in the large atypical cells of noncutaneous ALCL compared with PC CD30-positive LPDs (median, 100% versus 94%; P = .003) because of the lower expression of CD95 in LyP. CD95L expression was higher in the surrounding small lymphocytes in PC CD30-positive LPDs (median, 3% versus 13%; P = .002). Expression of CD95 in the small lymphocytes and CD95L in the large atypical cells was not significantly different. These results support the biologic distinction between cutaneous and noncutaneous CD30-positive LPDs and may have implications in the differing clinical behavior of these entities. Further study of expression and function of apoptosis-related proteins in these entities is warranted.     

Clinicopathologic analysis of 22 cases of subcutaneous panniculitis-like CD56- or CD56+ lymphoma and review of 44 other reported cases

In 22 histologic cases of subcutaneous panniculitis-like lymphoma, we studied the clinicopathologic differences between CD56- and CD56+ cases (11 each). CD56- cases had skin ulcers (1 [9%]); tumor invasion in the superficial dermis (1 [9%]); erythrophagocytosis (10 [91%]); and medium-sized (11 [100%]), CD8+ (10 [91%]), T-cell receptor (TcR)betaF1+ (10 [91%]), and CD95 (Fas)- tumor cells. CD56+ cases had skin ulcers (9 [82%]); tumor invasion in the superficial dermis (8 [73%]); erythrophagocytosis (1 [9%]); and pleomorphic large (10 [91%]), CD8+ (2/10 [20%]), TcRbetaF1 + (3/10 [30%]), and CD95 (Fas)+ (7/10 [70%]) tumor cells. These 7 factors were significantly different between groups (P < .01). Median survival rates were 96 and 12 months for the CD56- and CD56+ groups, respectively. Age younger than 40 years, no skin ulcers, no tumor invasion in the superficial dermis, and CD8+, TcRbetaF1 +, CD95 (Fas)-, and CD56- tumor cells were significantly better prognostic factors (P < .01). The CD56- and CD56+ groups showed different tumor cell characteristics, clinicopathologic findings, and prognosis. In the CD56+ group, 1 was gamma/delta T-cell phenotype, 3 were alpha/beta T-cell, and 6 were TcRbetaF1- and gamma/delta- NK/T-cell, and 3 NK/T-cell cases had nuclear signals of Epstein-Barr virus-encoded RNA. Cases of CD56+ T- and NK/T-cell lymphoma had similar clinicopathologic findings and prognosis.     

Diffuse large B-cell lymphoma with anaplastic features and focal low-grade mucosa-associated lymphoid tissue lymphoma component of the stomach

We describe an 83-year-old man diagnosed as having diffuse, large B-cell lymphoma with anaplastic features and CD30 expression of the stomach. Focally, the tumor showed typical low-grade mucosa-associated lymphoid tissue lymphoma. We are not aware of a previous report on the transformation of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type into an "anaplastic," large B-cell tumor.     

Secondary pleural involvement by an AIDS-related anaplastic large cell (CD30+) lymphoma simulating metastatic adenocarcinoma

We report a patient with acquired immunodeficiency syndrome with secondary pleural and pulmonary involvement by a CD30+ anaplastic large cell lymphoma (ALCL) that morphologically simulated metastatic adenocarcinoma. We describe the morphologic findings in order to heighten awareness that CD30+ ALCL may mimic metastatic adenocarcinoma in a body fluid or bronchial brushing and should be considered in the differential diagnosis. Primary body cavity based (PCBC) AIDS-related lymphoma is a relatively newly described disease entity with morphologic features bridging ALCL and large cell immunoblastic lymphoma with a CD30+ null immunophenotype. A morphology mimicking adenocarcinoma has not been previously described in this entity but should be considered in a patient with AIDS presenting exclusively with a serous effusion. Appropriate immunoperoxidase staining should aid in these differential diagnoses. Diagn. Cytopathol. 1998;18:113–117. © 1998 Wiley-Liss, Inc.