HODGKIN'S DISEASE ACCOMPANIED WITH THYMOMA

An autopsy case of Hodgkin's disease accompanied with thymoma is reported. The patient died of acute interstitial pneumonitis 9 years after the development of lymphadenopathy. On post-mortem examination thymoma was recognized. We believe that the present case is a very rare Hodgkin's disease complicating thymoma. The occurrence of second neoplasia in Hodgkin's disease is also discussed.     

Hodgkin's disease coexistent with plasma cell dyscrasia.

We describe a case of Hodgkin's disease, mixed cellularity type, associated with nodal monotypic plasma cells and monoclonal serum gammopathy. Although plasma cells are often found in tissues involved by Hodgkin's disease and may be numerous, the occurrence of Hodgkin's disease with monotypic plasmacytosis and/or monoclonal serum gammopathy is rare. The simultaneous occurrence of Hodgkin's disease and monotypic plasma cell proliferation may represent a coincidental occurrence. However, previously we have described cases of Hodgkin's disease associated with B-cell non-Hodgkin's lymphoma, perhaps suggesting a relationship between the Reed-Sternberg and Hodgkin cells and B-lineage lymphoid cells. The case presented further extends these observations.     

A primary mediastinal Hodgkin's lymphoma with asymptomatic myasthenia gravis: a rare association

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder that is frequently associated with other autoimmune diseases. It has been only rarely reported in association with thymic Hodgkin's lymphoma. We report a case of a 22-year-old man who presented with thoracic symptoms. Clinical examination was normal. Simple chest radiography showed a heterogeneous mediastinal mass. Thoracic computed tomography revealed an antero-superior mediastinal mass measuring 6 cm and invading the upper lobe of the left lung with parenchymal micronodules of the left lung and an involvement of mediastinal nodes. In order to consider a diagnosis of thymoma, electromyography was performed despite the fact that the patient was asymptomatic. This exam demonstrated signs specific of MG. After stabilising the MG with symptomatic therapies, surgical intervention was performed. Histological and immunohistochemical findings led to the diagnosis of thymic Hodgkin's lymphoma. The MG regressed completely after surgical removal of the lesion. The patient is currently receiving complementary chemotherapy. An association between asymptomatic MG and thymic Hodgkin's lymphoma has not been documented in the literature, and the present case appears to be the first reported. The pathogenesis of this association remains unknown. Some authors support a genetic origin, while others propose a hypothesis based on immunological studies. The treatment of thymic Hodgkin's lymphoma is based on Cotswold staging system. Nonetheless, MG generally regresses after surgical removal of the thymic lesion.     

A case report of sclerosing thymoma of the anterior mediastinum: an exceedingly rare morphology

The morphology of thymoma is diverse, although 5 basic subtypes are recognized in the World Health Organization classification system. Sclerosing thymoma was first documented in 1994 and to date only 13 cases have been reported. Sclerosis itself is considered to be an ancient change and can occur in various histological subtypes. Herein, we present a case of a 62-year-old woman incidentally found to have an anterior mediastinal mass, 31 × 24 × 17 mm in size, without an associated autoimmune disease such as myasthenia gravis. The mass was finally diagnosed as sclerosing thymoma derived from type A thymoma. Intraoperative pathological examination using a limited amount of sample did not allow a definitive diagnosis of thymoma in this case. When dealing with fibrous lesions observed in limited samples such as biopsy and intraoperative frozen specimens, recognizing sclerosing thymoma is important since there are several disease entities accompanying fibrosis in the anterior mediastinum.     

Non-Hodgkin's lymphoma of the central nervous system after treatment of Hodgkin's disease

A case of a 34-year-old man with stage IIIB nodular sclerosis Hodgkin's disease complicated by the development of a central nervous system non-Hodgkin's lymphoma is described. The second tumor became symptomatic eight months after the initial diagnosis of Hodgkin's disease, but a tissue diagnosis was not made until autopsy two months later. The Hodgkin's disease was, at that time, in remission, and the autopsy revealed no persistent or recurrent Hodgkin's disease. Despite radiotherapy, the brain lymphoma had progressed to involve the spinal leptomeninges extensively, but there was no lymphoma outside the central nervous system (CNS) at autopsy. The significance of this unique case is discussed in light of the known risk for non-Hodgkin's lymphoma as a second malignancy after Hodgkin's disease and in view of recent information concerning CNS lymphoma.     

Primary Adenoidal Hodgkin's Disease: Report of a Case with an Unusual Morphology and Review of the Literature

The nasopharyngeal lymphoid tissue (adenoids) is an uncommonly reported primary site for Hodgkin's disease. We report a case of primary adenoidal, interfollicular, epithelioid cell-rich variant of mixed cellularity Hodgkin's disease. The combination of an interfollicular pattern and richness of epithelioid histiocytes made it very difficult to make the diagnosis of Hodgkin's disease without the help of immunohistochemistry. To our knowledge, only 39 cases of Hodgkin's disease primarily involving the Waldeyer's ring have been reported in the English literature, 24 of these primarily involving the adenoids. Our case shows the difficulty encountered in making the diagnosis when a very unusual morphologic appearance of Hodgkin's disease is seen at a rare presentation site. The appropriate immunohistochemical work-up should be performed in unusual lymphohistiocytic proliferations involving the Waldeyer's ring. Int J Surg Pathol 8(3):241-246, 2000     

MINIMAL CHANGE RENAL DISEASE ASSOCIATED WITH THYMOMA AND PANCREATIC CARCINOMA

A case of minimal change renal disease associated with thymoma and pancreatic carcinoma is reported. A clinical manifestation of nephrotic syndrome developed about 5 weeks before the patient's demise and two different primary tumors were revealed only at the time of autopsy. Circumstantial evidences support that minimal change disease was a paraneoplastic process related to thymoma rather than either the one related to pancreatic carcinoma or a mere coincidence. Review of the literature disclosed five cases of thymoma with associated nephrotic syndrome. Herein, we report another case of such an unusual association and compare the present case with the previously reported.     

An unusual case of spontaneous remission of Hodgkin's disease after a single cycle of COPP-ABV chemotherapy followed by infectious complications

Advanced Hodgkin's disease is usually treated with six or more cycles of combination chemotherapy. Spontaneous regression of the cancer is very rarely reported in patients with Hodgkin's disease. We present an unusual case of a patient with Hodgkin's disease who experienced complete remission with a single cycle of chemotherapy, followed by pneumonia. The case was a 36-year-old man diagnosed with stage IVB mixed cellularity Hodgkin's disease in November 2000. After treatment with one cycle of COPP-ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine) chemotherapy without bleomycin, the patient developed interstitial pneumonia and was cared in the intensive care unit (ICU) for two months. Follow-up chest computerized tomography (CT), performed during the course of ICU care, revealed markedly improved mediastinal lymphomatous lesions. Furthermore, follow-up whole body CT and 18-fluorodeoxyglucose positron emission tomography showed complete disappearance of the lymphomatous lesions. Four years later, the patient is well and without relapse. This report is followed by a short review of the literature on spontaneous regression of Hodgkin's disease. To the best of our knowledge, this is the first case report of spontaneous remission of Hodgkin's disease in Korea.     

Hodgkin's disease of the endometrium

We report a case of Hodgkin's disease of the endometrium. The endometrial stroma is replaced by a polymorphic cellular infiltrate in which Reed-Sternberg cells are seen. The patient also has a history of stage IV-B Hodgkin's disease that was diagnosed and treated three years earlier. To our knowledge, Hodgkin's disease of the endometrium has not been described.     

Monoclonal antibodies reactive in routinely processed tissue sections of malignant lymphoma, with emphasis on T-cell lymphomas

The immunoreactivity of eight monoclonal antibodies was evaluated on 45 routinely processed lymphomas (22 T-cell lymphomas, 11 B-cell lymphomas, and 12 cases of Hodgkin's disease). Two antibodies reactive with leukocyte common (T200) antigens (PD7/26 and 2B11) stained most of the B- and T-cell lymphomas but did not stain the Reed-Sternberg cells and variants in Hodgkin's disease. Two antibodies known to stain B cells (LN-1 and LN-2) reacted with some of the B-cell lymphomas, but LN-2 also reacted with the neoplastic cells in six of 22 T-cell lymphomas and with the Reed-Sternberg variants in eight of 12 cases of Hodgkin's disease. The granulocyte antibody anti-Leu M1 reacted with most cases of Hodgkin's disease but also reacted with two of 11 B-cell non-Hodgkin's lymphomas. An antibody to epithelial membrane antigen (anti-EMA) stained some cases of T-cell lymphoma, B-cell lymphoma, and Hodgkin's disease. Leu 7 was expressed in one T-cell lymphoma and in one case of Hodgkin's disease. A novel antibody reactive with T cells (L60) stained all cases of T-cell lymphoma but also stained some cases of B-cell lymphoma and one case of Hodgkin's disease. We conclude that none of these antibodies, when used alone on routinely fixed paraffin-embedded material, is completely sensitive and specific for T-cell lymphoma, B-cell lymphoma, or Hodgkin's disease. However, a panel of antibodies is useful in distinguishing Hodgkin's disease from non-Hodgkin's lymphoma and in suggesting the B- or T-cell phenotype of non-Hodgkin's lymphomas.     

The original illustrations of Hodgkin's disease

In this report, the illustrations from the original papers on Hodgkin's disease are used to trace its early history. Thomas Hodgkin's report included six cases of his own and a seventh given to him by Robert Carswell, whose beautiful colored pictures of the latter case accompanied Hodgkin's presentation. Early clinical pictures are also presented. The histologic definition of the disease, with its characteristic cell, is traced with drawings from the reports of Greenfield, Sternberg, Reed, and Andrews. Modern histologic and immunocytochemical confirmation (Leu-M1 reactivity) of some of Hodgkin's original cases, preserved at Guy's Hospital, London, UK, are also illustrated. It is concluded that not only did Hodgkin describe cases of Hodgkin's disease that meet present-day criteria, he also included at least one case of non-Hodgkin's lymphoma, a term that now might be considered a misnomer.     

The distinction of Hodgkin's disease from B cell lymphoma.

Workshop C included cases with a differential diagnosis of Hodgkin's disease and B cell lymphoma. In general, the cases could be placed into one of the following four major categories: (1) usual Hodgkin's disease versus T cell-rich B cell lymphoma; (2) syncytial Hodgkin's disease versus B large cell lymphoma; (3) nodular and/or diffuse lymphocyte-predominance Hodgkin's disease (LPHD) versus T cell-rich B cell lymphoma; and (4) LPHD with composite or discordant large cell lymphoma versus T cell-rich B cell lymphoma progressing to large cell lymphoma. A final case illustrated the differential diagnosis of B cell Hodgkin's disease, ie, nodular LPHD versus the cellular phase of nodular sclerosing Hodgkin's disease (NSHD). The cases from this session have been grouped into these five categories and tables have been constructed to highlight features favoring each of the diagnostic possibilities. A brief discussion is given after each case, and selected cases have been illustrated to demonstrate some of the unusual histologic features.     

Immune thrombocytopenia in Hodgkin's disease

Thrombocytopenic purpura of the idiopathic thrombocytopenic purpura (ITP) type is an unusual and poorly documented complication of Hodgkin's disease. In an eight year period, three patients out of 140 with Hodgkin's disease developed thrombocytopenia; two of them presented a clinical picture undistinguishable from classic ITP. In both platelet antibody could be demonstrated. The third patient developed thrombocytopenia during an acute exacerbation of the underlying disease. Successful therapy of thrombocytopenia was achieved by methylprednisolone alone in one case and by cyclophosphamide in combination with methylprednisolone in the other two cases. These case reports demonstrate again that thrombocytopenia in Hodgkin's disease take place in active phases as well as in periods of complete remission; in the latter thrombocytopenia may reflect a part of immunological imbalance closely related to the pathophysiological background of Hodgkin's disease.     

Hodgkin's disease: immunoglobulin heavy and light chain gene rearrangements revealed in single Hodgkin/Reed-Sternberg cells.

AIM: To corroborate and investigate the nature of Hodgkin/Reed-Sternberg cells (H/R-S) of various subtypes of Hodgkin's disease. METHOD: Single H/R-S cells were micro-picked from frozen sections of tissues affected by Hodgkin's disease. The DNA from these cells was amplified by the polymerase chain reaction (PCR) with immunoglobulin heavy chain (IgH) gene FRIIIa/JH primers and light chain gene family specific primers. RESULTS: Fifty two of 135 isolated cells gave specific reaction products (36%). IgH and V kappa 4 gene rearrangements were found repeatedly in many H/R-S cells from one case of lymphocyte predominant Hodgkin's disease. Repeated V kappa 4 and individual IgH/V kappa 4,2 rearrangements were seen in one case, and individual IgH and V lambda 3/V kappa 4 rearrangements were seen in another case of nodular sclerosis-type Hodgkin's disease. Repeated IgH/V lambda 3 and individual V lambda 2,4 rearrangements, repeated V kappa 4 and individual IgH/V kappa 3 rearrangements, and repeated IgH and individual V kappa 3/V kappa 4 rearrangement were detected, respectively, in three cases of mixed cellularity-type Hodgkin's disease. Repeated and individual IgH rearrangements were found in another two cases of mixed cellularity-type Hodgkin's disease. CONCLUSION: The H/R-S cells isolated from lymphocyte predominant Hodgkin's disease had IgH and V kappa 4 gene rearrangements, which supports the conclusion that this disease results from a proliferation of neoplastic B cells. The IgH and kappa and/or lambda gene rearrangements seen in H/R-S cells isolated from classic Hodgkin's disease (mixed cellularity-type and nodular sclerosis-type) support the theory that these cells derive from B lineage cells at various stages of differentiation. To our knowledge, this is first time that lambda gene rearrangements have been detected in H/R-S cells.     

Paraneoplastic vanishing bile duct syndrome in a case of Hodgkin's disease

We report the case of a man whose Hodgkin's disease was diagnosed at the same time as ductopenia. Cholestasis partially regressed after lymphoma was treated. When Hodgkin's disease relapsed two years later, cholestasis reappeared and liver biopsy again showed ductopenia. Treatment of relapse resulted in remission and cholestasis resolved. Liver biopsies never showed infiltration by lymphoma during the course of the disease. The usual causes of ductopenia were ruled out. This case report emphasizes that paraneoplastic ductopenia may complicate Hodgkin's disease. Such ductopenia may evolve towards biliary cirrhosis and require liver transplantation.     

Detection of immunoglobulin heavy chain gene rearrangements in Hodgkin's disease using PCR.

AIM--To detect clonal rearrangements of the immunoglobulin (Ig) heavy chain gene in Hodgkin's disease tissue using the polymerase chain reaction (PCR). METHODS--DNA extracted from 36 samples of Hodgkin's disease was analysed using PCR and primers from conserved sequences in the variable (VH) and joining (JH) regions. RESULTS--Clonal rearrangement was detected only in one case. Evidence of clonal immunoglobulin gene rearrangement had been detected previously in this case using conventional Southern blot analysis. CONCLUSIONS--The sensitivity of the two techniques is equivalent and clonal Ig heavy chain gene rearrangements are rare in Hodgkin's disease.     

Progressive transformation of germinal centers with and without association to Hodgkin's disease

Progressively transformed germinal centers occurred in about 3.5% of cases of chronic nonspecific lymphadenitis. They are larger than germinal centers and are composed of follicular mantle lymphocytes, small clusters of proliferating mainly medium-sized B- and T-cells, as well as an extensive network of follicular dendritic cells. Sixty-six patients with lymph node enlargement containing progressively transformed germinal centers and staging and sequential biopsies of 213 patients with Hodgkin's disease (mixed and nodular sclerosis type) were investigated with special reference to the relationship of this lesion to Hodgkin's disease. In most cases, progressively transformed germinal centers developed without any obvious signs of illness and seemed to have no association with Hodgkin's disease. The patients could be differentiated into two groups. The larger group, Group 1 (n = 55 of 66) consisted of patients showing progressively transformed germinal centers without association to Hodgkin's disease. The smaller group, Group 2 (n = 11 of 66) showed progressively transformed germinal centers obviously with association to nodular paragranuloma (Hodgkin's disease lymphocytic predominance type). Progressively transformed germinal centers preceding (n = 3), simultaneously (n = 4), and after development of nodular paragranuloma (n = 4) were found. With regard to subtypes of Hodgkin's disease other than paragranuloma, progressively transformed germinal centers also could be found in sequential biopsies of Hodgkin's disease of mixed and nodular sclerosis type. In one case, progressively transformed germinal centers preceded, in another case they occurred simultaneously in mixed type of Hodgkin's disease, and in two cases of nodular sclerosis type progressively transformed germinal centers developed after the onset of Hodgkin's disease. These findings suggest that progressively transformed germinal centers may be a result of different processes that may be occasionally related not only to nodular paragranuloma, but also in rare cases to nodular sclerosis and mixed type of Hodgkin's disease.     

Coexisting mycosis fungoides and Hodgkin's disease as a composite lymphoma: a case report.

Within the past few years, an increasing number of reports of Hodgkin's disease following the diagnosis of, and frequently coexisting with, mycosis fungoides have appeared. Previously, Hodgkin's disease found in the lymph nodes of the patient diagnosed as mycosis fungoides was considered as a transformed form of the mycosis fungoides. But, now it has been proven that Hodgkin's disease and mycosis fungoides are histologically and immunohistochemically distinct disease entities. We report a well-documented case of a man who developed Hodgkin's disease and mycosis fungoides simultaneously as a composite lymphoma. Our case emphasizes the importance of considering the diagnosis of another lymphoma in patients with mycosis fungoides who have lymphadenopathy. The cutaneous mycosis fungoides and the Hodgkin's disease should be treated as an independent disease.     

CD20-Positive peripheral T-cell lymphoma: report of a case after nodular sclerosis Hodgkin's disease and review of the literature.

We present a case of peripheral T-cell lymphoma co-expressing CD3 and CD20, as well as demonstrating T-cell receptor gene rearrangement, in a patient who had been diagnosed with nodular sclerosis Hodgkin's disease 5 years previously. Although 15 cases of CD20-positive T-cell neoplasms have been previously reported in the literature, this is the first report of CD20-positive T-cell lymphoma occurring subsequent to treatment of Hodgkin's disease. The current case affords an opportunity to review the rarely reported expression of CD20 in T-cell neoplasms as well as the relationship between Hodgkin's disease and subsequently occurring non-Hodgkin's lymphomas. In addition, the identification of this case supports the suggestion that the use of CD20 antibodies alone in paraffin sections may lead to an incorrect determination of cell lineage in some cases.     

Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin

Fifteen cases of non-Hodgkin's lymphoma of the anterior mediastinum are reported. In the first group of four, fresh tissue was available and immunohistochemical studies demonstrated their B-cell origin, with monotypic immunoglobulin production in two. Only fixed tissue was available in the second group of 11 patients. All stained with antibody to leucocyte common antigen (PD7/26) and three showed monotypic immunoglobulin production. If the two groups are combined seven of the 15 tumours were clearly of B-cell origin. Classification on morphological grounds was difficult, with most tumours showing mixtures of centroblasts and large centrocytes, and the original diagnoses had included Hodgkin's disease (three), thymoma (one) and undifferentiated carcinoma (two). None of the patients had evidence of extra-thoracic disease at presentation and when this developed the organs involved were liver (one), kidney (two) and thyroid (one). Direct extension within the chest led to infiltration of chest wall, sternum, lung, superior vena cava and other structures. The site of origin, lack of nodal involvement and, in one case, presence of residual thymus around the tumour indicate an origin in thymic B-cells.