[Coccidioidomycosis presenting as a pulmonary nodule after pneumonia]. / Opacité tumorale apparue au decours d'une pneumonie fébrile révélant une coccidioïdomycose thoracique.

Coccidioidomycosis is a fungal infection endemic in the south west of the United States. Sixty percent of infected individuals remain asymptomatic. Symptomatic disease manifests itself with variable signs such as pneumonia, pleural effusion, empyema or acute respiratory distress syndrome. Residual disease includes pulmonary nodules and fibrosis. We report a case of a woman, returning from a trip to Arizona, presenting with an acute respiratory infection associated with erythema nodosum and arthralgia. She was successfully treated with routine antibiotics. The acute pneumonia resolved and the radiological infiltrate contract into a solitary pulmonary nodule. We suspected a malignant nodule in a previous smoker. The diagnosis of pulmonary Coccidioidomycosis was made after surgical resection. One year later, the patient is asymptomatic and well. This review focuses on the most common clinical manifestations, the diagnostic strategy and the treatment and management of pulmonary Coccidioidomycosis.

Production of monoclonal antibodies to human estrogen-receptor protein (ER) using recombinant ER (RER).

Two monoclonal antibodies (MAbs), IC5 and ID5, were produced using spleen cells from BALB/c mice immunized with recombinant estrogen-receptor protein (RER). On immunoblotting, both MAbs reacted with the 67-kDa polypeptide chain obtained by transformation of E. coli and transfection of COS cells with plasmid vectors expressing ER. The epitopes of both MAbs were in the N-terminal domain (A/B region) of the receptor. In normal human tissues, IC5 and ID5 reacted with cells known to contain large amount of ER, such as cells of the mammary gland and the uterus. Staining was localized predominantly in nuclei with little or no cytoplasmic reactivity. IC5 and ID5 were unreactive with tissues usually considered to be negative for ER. The reactions of these 2 MAbs were further tested on different tumor types, using immunohistochemical (IHC) method on frozen sections. In breast cancer, a good correlation was found between the results obtained on frozen sections and those using the conventional radioligand dextran-coated charcoal (DCC) assay. Immunostaining with IC5 and ID5 MAbs was also assessed on routinely processed paraffin sections using the antigen-retrieval method. Staining was comparable to that obtained on frozen sections in virtually all the breast carcinomas. Negative reactions were consistently obtained with both antibodies on human neoplasms derived from other non-estrogen-dependent organs. IC5 and ID5 MAbs may thus be of value in routine diagnostic histopathology for assessment of the estrogen-receptor content in human carcinomas.

Immunophenotyping of mesothelial cells and carcinoma cells with monoclonal antibodies to cytokeratins, vimentin, CEA and EMA improves the cytodiagnosis of serous effusions.

This paper presents an immunocytochemical study performed on cytocentrifuged deposits from 109 peritoneal and pleural effusions including 20 transudates, 43 malignant metastatic effusions and 46 effusions containing atypical cells, unidentifiable as reactive mesothelial or malignant epithelial cells on the classical morphological criteria. A panel of four monoclonal antibodies (MAb) was used, including KL1 directed to cytokeratins (KER), V9 to vimentin (VIM), NEO 723 to carcinoembryonic antigen (CEA) and E29 to epithelial membrane antigen (EMA). In most transudates the reactive mesothelial cells coexpressed VIM and KER with a ring-like pattern for the latter proteins. In contrast, they were unreactive to anti-CEA and weakly and inconsistently reactive to anti-EMA. In malignant effusions, most carcinoma cells coexpressed EMA, CEA and KER with a predominant diffuse cytoplasmic pattern for the latter. Only a few malignant epithelial cells from five metastatic adenocarcinomas weakly expressed VIM. When used on the 46 effusions with unidentifiable cells, the panel of MAb allowed reactive mesothelial cells and malignant epithelial cells to be distinguished from each other in 39 of 46 cases (85%).

Immunohistochemical profile of cutaneous B-cell lymphoma on cryostat and paraffin sections.

Thirty cases of primary (23 cases) and secondary (seven cases) cutaneous B-cell lymphoma (CBCL) were studied by immunohistochemistry using a selected monoclonal antibody (MoAb) panel on both cryostat and paraffin sections. On cryostat sections all CBCL so tested were positive for surface membrane immunoglobulins (IgMk most often) and B-cell antigens (CD22+, CD37+) with a variable T-cell-reactive component identified by MoAbs against T-cell antigens (CD2, CD3, CD4, CD5, CD8). CD4-positive stromal T-cells were usually more numerous than CD8-positive cells. A strong (50-75% of total cells) stromal T-cell (CD2+, CD3+) reaction was found in centroblastic-centrocytic lymphoma. Small numbers of CD1+ Langerhans cells were found in most cases, but they were present in large numbers in follicular lymphoma. On paraffin sections, a combination of MoAbs against B-associated antigens (LN-1, MB2) identified B-cell lineage in virtually all cases of CBCL. CBCL was negative for MoAbs against T-associated antigens (MT1, UCHL1) with rare exceptions (two cases). However, MT1 and UCHL1 combined identified the T-cell nature of all cases of nonepidermotropic, nonmycosis T-cell lymphoma, which were initially predictive of B-lineage by histologic pattern.

[Giant uterine leiomyoma and pregnancy. Clinical, radiologic, unusual histopathologic aspects]. / Léiomyome utérin géant et grossesse. Aspects cliniques, radiologiques, histopathologiques inhabituels.

The authors report a case of uterine leiomyomas diagnosed during the first trimester of pregnancy. The most unusual presentation of this observation did not allow any diagnosis through clinical exam, either by sonographic and X ray technics (magnetic resonance imaging, computer tomography) or by the classical histological study. The intra abdominal tumors compatible with imagery are argued: ovarian cyst, gelatinous disease of the peritoneum, desmoid tumor, lymphoma, lymphangiomyoma. The right diagnosis has been established as a last resort to immunocytochemistry.

[Cells of the phenotype HNK-1 + (CD 57 +) in reactive adenopathies, lymphomas and Hodgkin's disease]. / Les cellules de phénotype HNK-1 + (CD 57 +) dans les adénopathies réactionnelles, lymphomateuses et Hodgkiniennes.

The number and distribution of Leu-7 + cells, a subset of Natural Killer cells clustered as CD 57 + cells, were studied with an immunoperoxidase technique on reactive lymph nodes (n = 13), malignant lymphomas (n = 60) and Hodgkin's disease (n = 22). Results of paraffin-section immunocytochemistry were compared with those obtained of frozen sections of the same tissues. CD 57 + cells are small lymphocytes mainly located in the germinal centers of reactive lymph nodes and in their malignant counterpart, i.e. the follicular lymphomas. The paragranuloma of Hodgkin's disease, type I nodular, contained high numbers of CD 57+ cells. Nine cases of CD 57+ lymphomas are reported, which were of high grade of malignancy. Their histological subtypes were anaplastic (3 cases) immunoblastic (2 cases), pleomorphic medium and large cell (3 cases), unclassifiable (1 case). Their diverse T-cell (4 cases) or B-cell (2 cases) origin and the various expression of epithelial membrane antigen (EMA) or Kil/Ber-H2 (CD 30) suggest an aberrant CD 57+ phenotype of a subset of large cell lymphomas.

Production of anti-B monoclonal antibodies (DBB.42, DBA.44, DNA.7, and DND.53) reactive on paraffin-embedded tissues with a new B-lymphoma cell line grafted into athymic nude mice.

A new B-lymphoma cell line (DEAU-cell line) was established from a diffuse large-cell lymphoma (centroblastic type) and was successfully grafted in athymic nude mice. Monoclonal antibodies (MoAbs) were generated using splenocytes of DEAU-tumor bearing mice. Before the fusion experiments, cellular immunity of the mice bearing growing DEAU tumors was restored by injection of spleen cells from conventional Balb/C mice. Spleen cells from conventional Balb/C mice immunized with DEAU-cell line were also used for the generation of MoAbs. Four MoAbs (DBB.42 and DBA.44 from normal Balb/C mice, and DNA.7 and DND.53 from athymic nude mice) were investigated because they identified B-cell-associated antigens not destroyed by fixatives. DBB.42 recognized a pan-B cell-associated antigen (molecular weight (mol wt) = 45 Kd). DBA.44 detected a B-cell antigen (mol wt not determined) expressed on a subpopulation of B lymphocytes in the mantle zone of lymphoid follicles. DNA.7 also defined a B-cell antigen (43 Kd) mainly expressed on germinal center cells. Similarly, DND.53 recognized a B-cell antigen (two bands of mol wt 20 Kd and 35 Kd, respectively) mainly expressed on germinal center cells and mantle zone lymphocytes and interdigitating reticulum cells in the paracortical area. Major differences were found in the reactivities of these MoAbs on malignant lymphomas. DBB.42 was positive with almost all B-cell lymphomas and some T-cell lymphomas. Within the group of low-grade B-cell lymphomas, DBA.44 reacted principally with hairy-cell leukemia. DNA.7 reacted mainly with high-grade B-cell lymphomas with a weak positivity in low-grade B-cell lymphomas. DND.53 reacted with all but one B-cell lymphoma, cells of histiocytosis X, and Reed-Sternberg cells. These findings indicate that new MoAbs can be generated by using spleen cells from athymic mice bearing human tumors as well as by new lymphoid cell lines. The MoAbs so generated, as in the present study, are deemed potentially useful for the recognition of B-cell lymphomas in routine diagnostic histopathology. In addition, DND.53 could be of value for the diagnosis of histiocytosis X and the detection of Reed-Sternberg cells in Hodgkin's disease.

Immunohistochemical demonstration of leucocyte differentiation antigens on paraffin sections using a modified AMeX (ModAMeX) method.

The AMeX method (cold Acetone fixation with subsequent Methyl benzoate and Xylene treatment and routine paraffin embedding) has been recently revived for simultaneous preservation of morphology of cells and their antigens. We propose a modification of this method (ModAMeX), with the use of proteolytic enzyme inhibitors and low temperature paraffin wax embedding, which results in better preservation of a large number of leucocyte differentiation antigens and diagnostic morphologic detail. T-cell antigens (CD1, CD2, CD3, CD7 & CD8), B-cell antigens (CD22), macrophage associated antigens (CD11c, CD14 and others), activation antigens (CD25 and others), as well as some other antigens of diagnostic interest (CD10) were found to be preserved with a staining intensity equal to that of sections of fresh frozen tissue. Although the staining intensity of other T-cell antigens (CD4 & CD5), B-cell antigens (CD19, CD21 & CD37), activation antigens (Ki-1) and nuclear proliferation antigen (Ki-67) was slightly weaker as compared with frozen sections, this could be corrected by increasing the monoclonal antibody concentration. Staining for heavy and light chains of immunoglobulins was minor, sometimes compromised due to persistence of background staining as a result of extracellular immunoglobulins. The ModAMeX method has the advantages of simplicity, low cost and the possibility of exchange of tissue material between laboratories.

[Immunochemical diagnosis of hepatic localizations in malignant lymphoid hematologic diseases. Study of 80 cases]. / Diagnostic immunohistochimique des localisations hépatiques des hémopathies lymphoïdes malignes. Etude de 80 cas.

The diagnostic value of immunohistochemistry using monoclonal antibodies was assessed in 100 liver biopsy specimens. The majority of these cases were hepatic localizations of lymphoid malignancies. Ten normal and reactive inflammatory liver biopsies were used as controls. Some monoclonal antibodies directed against leukocyte antigens revealed unexpected reactivities with normal liver structures: biliary tract (anti-CD10, anti-B MB2) and hepatocytes (anti-B LN1). In 12/17 cases of hepatic involvement by large cell malignancy, immunohistochemistry allowed the diagnosis of non Hodgkin's lymphoma (NHL); the remaining 5 cases were metastatic undifferentiated carcinoma. It was difficult to differentiate small cell liver NHL from reactive inflammatory infiltration. New anti-B (MB1, MB2, 4KB5, LN1 and LN2) and anti-T (MT1 and UCHL1) monoclonal antibodies suitable for use on paraffin sections were of value to phenotype NHL when only fixed material was available. But, information was too limited to distinguish malignant from reactive infiltrates. Immunohistochemistry on frozen sections was often necessary to diagnose inflammatory infiltrates and to phenotype NHL. Most NHL were of B cell origin (11/13 cases) and showed monotypic surface immunoglobulins as well as B cell-associated antigens (CD22+). The expression of the T CD5 antigen by B-cell NHL may have some diagnostic value. When monotypic surface immunoglobulins could not be demonstrated (due to background staining) the expression of this antigen by B lymphocytes was considered to be highly indicative of their neoplastic nature. Hairy cell leukemia exhibited a pathognomonic phenotype on frozen sections (CD11c+, CD22+, CD25+). T NHL were rare (2 cases) and difficult to diagnose due to the lack of clonal markers. The diagnosis of Hodgkin's disease in liver (15/20 cases) was facilitated by using paraffin sections of both monoclonal antibodies anti-CD15 (Leu M1) and anti-CD30 (Ber-H2) which detect fixation-resistant antigens expressed by Sternberg cells.

Stage IE nonHodgkin's lymphoma of the testis: a need for a brief aggressive chemotherapy.

Primary nonHodgkin's lymphoma of the testis is a localized disease in 50 per cent of the cases. Clinical records and pathological material from 9 stage IE cancer patients treated at our institutions were reviewed. All but 1 patient had B cell type lymphomas of intermediate (6) or high (3) grade according to the Working Formulation. Mean survival was 49 months and actuarial survival was 74 per cent at 5 years. Chemotherapy differed with time and frequently was associated with subdiaphragmatic involved field and prophylactic contralateral testis radiotherapy. In view of the good prognosis of patients receiving doxorubicin-based chemotherapy and recent reports on low stage nonHodgkin's lymphoma we recommend an aggressive brief therapy for stage IE lymphoma of the testis after orchiectomy.

Immunohistochemical detection of post-therapy residual testicular lymphoblasts in childhood acute lymphoblastic leukemia (ALL).

The aim of this study was to evaluate the diagnostic value of immunohistochemistry with monoclonal antibodies (MoAbs) in detecting residual blast cells in testicular biopsies from children with acute lymphoblastic leukemia (ALL). In a prospective study of 26 patients, testicular biopsies were performed after completion of therapy, and the average follow-up after biopsies was 29 months. After immunostaining, seven patients with negative biopsies on routine histology showed scattered, strongly calla-positive cells as well as cells reacting with anti-B (CD22) MoAb. Among these seven patients with residual blast cells, four had relapsed either in testes (n = 1), bone marrow and testes (n = 1), or in the bone marrow (n = 2). In contrast, among the 15 patients without residual blast cells, all but 1 remained in complete remission. In four other cases no definite conclusion was possible after immunohistochemical study. Four testicular biopsies from patients with occult infiltration were used as positive controls. Negative controls consisted of testicular biopsies from children with testicular ectopia and postmortem testicular tissue specimens. Results suggest that the risk of relapse is significantly higher in patients with positive immunohistochemical findings indicating persistent residual blast cells. However, the predictive value of these findings requires confirmation on a larger number of cases to have therapeutic implications.

Diagnostic features of primary malignant lymphomas of the thyroid with monoclonal antibodies.

Primary malignant lymphomas (ML) of the thyroid are rare and their conclusive morphologic diagnosis is not always possible. The authors report diagnostic features of 11 cases of ML and one case of plasmacytoma of thyroid compared with chronic lymphocytic thyroiditis and undifferentiated carcinomas of thyroid in an immunohistochemical study using monoclonal antibodies (MoAb). The lymphoid nature of tumors could be identified in all cases with three MoAb on paraffin sections. In ML, tumor cells expressed leucocyte common antigen (Dako-LC+) with negativity for epithelial membrane antigen (Dako-EMA-) and cytokeratin (KL1-). Newer MoAb identifying B-cell (LN-1, LN-2, MB2) and T-cell-associated antigens (MT1, UCHL1) not denatured by fixation, revealed B-cell nature of tumor cells in all cases of ML. Among anti-B MoAb, LN-1 and MB2 were most consistent in their reactivity. In cryostat sections of three ML cases, the tumor cells expressed one or more B-cell-associated antigens. Plasmacytoma was negative for Dako-LC and KL1 but positive for Dako-EMA and monotypic cytoplasmic Ig.

Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas. Diagnostic value in so-called malignant histiocytosis.

A group of 63 cases of anaplastic large cell lymphomas (variants of diffuse large cell lymphomas often diagnosed as "malignant histiocytosis") was characterized on both morphologic criteria and expression of epithelial membrane antigen (EMA) and Ki-1 antigen (CD30). On the basis of the reactivity of these tumors with anti-EMA and anti-Ki-1 antibodies, four subtypes could be distinguished. In the majority of cases (n = 49), neoplastic cells coexpressed EMA and Ki-1 antigens. Nineteen of these cases were tested for IL-2R, and all were positive (Type I, EMA+, Ki-1+, IL-2R+). In the second group (n = 5), the neoplastic cells expressed EMA but not the Ki-1 antigen. These cases were not tested for the presence of IL-2R (Type II, EMA+, Ki-1-, IL-2R?). There were tumors with similar morphology expressing only Ki-1 antigen (Type III, EMA-, Ki-1+, IL-2R-) or negative for both EMA and Ki-1 antigens (Type IV, EMA-, Ki-1-, IL-2R-). EMA appeared to occur predominantly on activated cells, as has been previously shown for Ki-1 antigen. Analysis using monoclonal antibodies to T-cell, B-cell, or macrophage-associated differentiation antigens showed that these tumors were heterogeneous in terms of cell lineage. Tumors coexpressing EMA, Ki-1, and IL-2R (Type I), were most commonly of T-cell origin (n = 12); the remainder in this type expressed B-cell markers (n = 4), a mixed B/T phenotype (n = 2), or no clear phenotype (n = 9). By contrast, tumors of Types II, III, and IV were mainly from B-cell origin (n = 6) or showed a mixed B/T phenotype (n = 1). Despite the fact that a significant proportion of these cases were initially classified morphologically as "malignant histiocytosis," only 3 of the 63 cases were possibly of histiocytic origin. These results confirm that true malignant histiocytosis is rare and that most tumors with histologic features currently regarded as being consistent with this diagnosis are lymphocytic in origin and express activation antigens such as EMA, Ki-1 antigen, and IL-2R.

Monoclonal antibodies in the diagnosis of Hodgkin's disease. The search for a rational panel.

A novel, comprehensive panel of monoclonal antibodies was tested in a large series of routinely processed lymph node biopsy specimens from patients with Hodgkin's disease (69 cases), with the object of developing either definitive or adjunctive diagnostic criteria. B- and T-cell lymphomas and reactive states that could mimic Hodgkin's disease were also assessed with the same monoclonal antibody panel. In addition to the popularly used anti-Leu-M1 (CD15), the panel included the recently produced Ber-H2 (CD30) antibody, which detects a formalin-resistant epitope of the Ki-1 antigen. The other monoclonal antibodies were directed against epithelial membrane antigen (Dako-EMA) and leukocyte common antigen (Dako-LC) (CD45), as well as B-cell (LN-1 and LN-2) and T-cell (MT1) associated antigens. The results showed clear phenotypic separation of nodular lymphocyte predominant subtype of Hodgkin's disease from other subtypes. The lymphocytic and histiocytic cells of nodular lymphocyte predominant Hodgkin's disease were reactive for LN-1 (all cases) and anti-EMA (most cases) but negative for anti-Leu-M1 and Ber-H2. Within the other subtypes--i.e. nodular sclerosis and mixed cellularity--nearly all Reed-Sternberg cells and Hodgkin's cells were positive for both anti-Leu-M1 and Ber-H2. Ber-H2 monoclonal antibody was observed to react more frequently with Reed-Sternberg cells and Hodgkin's cells in Bouin's- or formalin-fixed tissues. Pleomorphic T-cell lymphomas, which could mimic Hodgkin's disease on morphology, created the same problem on phenotypic analysis. However, MT1 identified a significant proportion of T-cell lymphomas with Reed-Sternberg-like cells, having proven negative for Reed-Sternberg cells and Hodgkin's cells in Hodgkin's disease. Thus, a combination of anti-Leu-M1, Ber-H2, anti-EMA, LN-1, and MT1 monoclonal antibodies appears at present to be the most useful panel for the diagnosis and the differential diagnosis of Hodgkin's disease.

[Contribution of immunohistochemical technics to the study of malignant infiltration of bone marrow]. / Apports des techniques immunohistochimiques à l'étude des infiltrations malignes de la moelle osseuse.

Immunohistochemistry using monoclonal antibodies has been proved of diagnostic value in bone marrow pathology. Several monoclonal antibodies identifying antigens not denatured by fixation are now available. In anaplastic tumors infiltrating bone marrow these antibodies allow the distinction of large cell lymphomas which express the leucocyte common antigen (Dako-LC+) from undifferentiated carcinomas which are reactive with anti-cytokeratin antibodies (KL-1+, Dako-EMA+), neuroblastoma (NSE+) and rhabdomyosarcoma (desmin+). KL-1 and Dako-EMA antibodies are also considered to be powerful tools to disclose micrometastases from carcinoma, particularly breast carcinoma, which otherwise may be undiagnosed. The detection of residual or minimal bone marrow involvement in malignant lymphomas (particularly Burkitt type) remains difficult. However, in some cases, Dako-LC and MB2 (anti-B) antibodies are useful to detect bone marrow involvement in some lymphoproliferative disorders composed of small or medium-sized cells scattered among hematopoietic cells, and in some large cell lymphomas (i.e. centroblastic or immunoblastic types). These antibodies allow the detection of minimal or residual involvement by malignant cells, which can be confused with immature hematopoietic cells, on routine stainings. No anti-T antibody was found to react satisfactorily with T cell on decalcified biopsy specimens. In anaplastic large cell lymphomas (so-called malignant histiocytosis), malignant cells coexpress Ki-1 and EMA antigens. Antibodies recognizing these two antigens were found to be of value to demonstrate scarce neoplastic cell in bone marrow.

Sinus histiocytosis with massive lymphadenopathy (Destombes-Rosai-Dorfman syndrome) occurring as a single enlarged submandibular lymph node: a light and immunohistochemical study with review of the literature.

Sinus histiocytosis with massive lymphadenopathy (SHML) is primarily a disease of children and young adults in which there is a pronounced and persistent cervical lymph node enlargement that usually is bilateral and is accompanied by fever. The histology, which varies according to the stage of the disease, is characterized by an exuberant intrasinusoidal histiocytic proliferation. The present case involves a 4-year-old girl who had several episodes of upper respiratory infection and otitis media; subsequently, a walnut-sized enlargement developed in the left anterior portion of the neck. Results of a physical examination were essentially normal. A laboratory work-up was noncontributory. Serologic tests for toxoplasmosis, infectious mononucleosis, and cat-scratch disease were negative. Immunoelectrophoresis disclosed normal values for IgG, IgM, IgA, and IgE. The histopathology was characteristic of SHML. The lymph node demonstrated pericapsular and capsular fibrosis and widely dilated subcapsular, trabecular, and medullary sinuses packed with histiocytes and plasma cells. "Lymphophagocytosis" and large atypical histiocytes resembling Reed-Sternberg cells were noted. Immunohistochemistry demonstrated a polyclonal population of plasma cells mostly stained with rabbit anti-human igG. The cytoplasm of the histiocytes, having ingested lymphocytes, was positively stained for IgG. Other groups of lymph nodes were affected during the next several months. The patient's condition has now been followed for 2 years, and the lymphadenopathy has almost completely regressed. The site distribution of the head and neck extranodal manifestations of SHML was analyzed in 54 cases.

Follicular lymphoma with abundant PAS-positive extracellular material. Immunohistochemical and ultrastructural observations.

A finding of large amounts of extracellular amorphous material is rare in malignant lymphomas. We report four such cases of follicular lymphoma that were investigated by electron microscopy and immunohistochemistry using monoclonal antibodies. This extracellular material was clearly different from the sclero-hyalinosis commonly found in malignant lymphomas. Our observations revealed that the material is ultrastructurally composed of membranous structures, membrane-bound vesicles, and electron-dense bodies. Immunohistochemistry confirmed its neoplastic cell origin and its identity with cell membrane antigens (Dako-LC+, anti-B antibodies positive). In one case investigated using frozen sections, it showed the same immunophenotype as the neoplastic cells: SB4+ (CD19), SB2+ (CD21), TO15+ (CD22), SB3+ (CD37), IgML+, and Calla+. The mechanism for accumulation of this extracellular amorphous material is probably a function of a deregulation of cell wall synthesis and an exocytosis of cell membranes.

Hodgkin's lymphoma of the oropharyngeal region: report of four cases and diagnostic value of monoclonal antibodies in detecting antigens associated with Reed-Sternberg cells.

In a review of more than 500 cases from the Lymphoma Registry, Department of Anatomic Pathology, University Hospital Purpan, Université Paul Sabatier, Toulouse, France, four cases of primary lesions in the oropharyngeal region were found. There were two lesions in the palatine tonsil, one in the nasopharynx, and one in the parotid gland. The average age of the patients was 54.5 years (range, 37 to 70 years), and all patients were men. The histologic types were lymphocyte predominance (one case), nodular-sclerosis (one case), and mixed cellularity (two cases). The patients were respectively staged as IAa, IIAa, and IIIA. They were treated with radiation, chemotherapy, or both. All four patients are now free of tumor and have been followed from 18 months to more than 6 years after definitive diagnosis and appropriate therapy. Immunohistochemistry significantly contributes to the differential diagnosis of atypical Hodgkin's disease from non-Hodgkin's lymphomas, especially in extranodal sites. Dako-EMA and Leu-M1 monoclonal antibodies are reactive, respectively, with L and H variants (Dako-EMA+, Leu-M1-) in the lymphocyte predominance type (Type 1) and with Reed-Sternberg cells (Dako-EMA-, Leu-M1+) in the nodular-sclerosis (Type 2), mixed cellularity (Type 3), and lymphocyte depletion (Type 4) types.