Extrahepatic Hodgkin's disease with intrahepatic cholestasis: report of two cases.

Liver is involved in about 5-8% of newly diagnosed Hodgkin's disease (HD) cases. The incidence reaches up to 50-60% in postmortem studies. In the literature only a few cases of idiopathic cholestatic jaundice have been described without an apparent cause and a paraneoplastic etiology has been suggested. We report 2 cases with HD presenting with obstructive jaundice without obvious liver involvement. The first case died soon after diagnosis; the second case received chemotherapy and radiotherapy, and she is well at 26 months' follow-up. Extrahepatic HD with intrahepatic cholestasis is an extremely rare situation without an established approach. Such cases like the present ones may help to understand the pathogenesis of the liver involvement of HD and determine the best management of these cases.     

Hodgkin's disease diagnosed post mortem: a population based study.

All cases of Hodgkin''s disease (HD) notified to the Danish Cancer Registry from 1976 through 1987 in patients less than 70 years old were reviewed in order to identify patients in whom a correct diagnosis was established only post mortem. The case records of such patients were reviewed in a search for clinical features that could have ensured a correct pre mortem diagnosis. HD was diagnosed after death in 31 patients in this unselected population based study and thus constituting only 2.4% of all patients less than 70 years with HD, but 14.1% of the group aged 65-69 years. Most patients were identified during the first part of the study period, which may reflect a decreasing autopsy rate. HD was considered to be a coincidental finding in four patients and the primary cause of death in 27 patients. Among the later 27 patients a number of unfavourable prognostic factors were a common finding: persistent unexplained fever and weight loss, pancytopenia, hepatic involvement, bone marrow involvement, advanced stage disease, and lymphocytic depletion histology. However, most of the patients had no concurrent diseases and may have benefitted from a correct diagnosis and a potentially curative treatment. The many uncommon features of HD together with the frequent findings of falsely negative chest X-ray, bone marrow examination, liver biopsy, and ultrasound contributed to the difficulty in diagnosis. In about 1/3 of the patients clinical findings suggestive of lymphoma did not result in relevant diagnostic procedures.     

桥本病及其合并甲状腺癌的诊治

目的　探讨桥本病及其合并甲状腺癌的诊断、治疗措施。方法　收集甲状腺手术病例 5 2 9例 ,分析 42例桥本病的甲状腺素、甲状腺微粒体抗体 (TMA)、球蛋白抗体 (TGA)的变化及其中 5例合并甲状腺癌时与桥本病、甲状腺结节之间的关系。结果　桥本病术前误诊率为 83 3%,桥本病的TSH、TMA、TGA显著升高 ,桥本病合并甲状腺癌发生率为 11 9%,肿块呈不规则结节表现时合并癌发生率为18 2 %;经个体化治疗 ,术后随访期间无甲低、癌复发转移病例。结论　桥本病误诊率高 ,术前常规测TSH、TMA、TGA升高有助于提高桥本病的诊断 ;对甲状腺不规则结节病例 ,应警惕桥本病合并癌可能 ;术中作冰冻切片 ,并遵循个体化原则手术 ,使治疗更有效。     

原发性上颌骨霍奇金淋巴瘤一例并文献复习

 目的　提高对原发性骨霍奇金淋巴瘤的诊断和治疗的认识,加强对其病理组织学和影像学表现特点的认识。方法　报道1例原发性上颌骨霍奇金淋巴瘤的临床表现、实验室特征和治疗经过,并复习国内外相关文献。结果　患者以右上颌骨疼痛起病,X线显示上颌骨右侧可见大片溶骨性破坏,破损边缘不清晰,有部分骨硬化表现。手术摘除肿块,病理检查为霍奇金淋巴瘤淋巴细胞消减型,临床诊断为右上颌骨原发性霍奇金淋巴瘤（Ⅰ期）。给予ABVD方案治疗,无明显不良反应。结论　原发性骨霍奇金淋巴瘤是一种非常罕见的骨恶性淋巴瘤,容易误诊,目前确诊主要依靠病理及免疫组织化学。应尽早明确诊断,并加以鉴别诊断,现代化疗方案的预后较好。     

Non-Hodgkin's lymphoma of the brain after Hodgkin's disease. An immunohistochemical study

Non-Hodgkin's lymphoma (NHL) of the central nervous system (CNS) is a rarely reported complication of Hodgkin's disease (HD). Two patients with NHL of the brain after HD were studied by histologic and immunohistochemical methods. Both patients were in the second decade, had been treated with radiation and chemotherapy, had experienced a relapse of HD before development of NHL, had no evidence of HD at the time of diagnosis of NHL, and died within 1 year of diagnosis. Both brain neoplasms were large cell immunoblastic lymphomas of B-cell lineage. Patients with HD appear to be at increased risk for NHL of the CNS, which may have a poor prognosis.     

Hodgkin's disease and AIDS. Twenty-three new cases and a review of the literature

Despite numerous reports suggesting an association of Hodgkin's disease (HD) with the acquired immunodeficiency syndrome (AIDS), HD in an individual seropositive for the human immunodeficiency virus (HIV) still is not considered a criterion for the diagnosis of AIDS. The authors report 23 new cases of HD in individuals at risk for AIDS and review the literature. As a group, individuals at risk for AIDS who develop HD have a more aggressive form of the illness (82% with stage III or IV), have or develop AIDS-related opportunistic infections (54%), second neoplasms (10%), and /or profound cytopenias (32%), and 85 to 90% are HIV positive when tested. More than two thirds die within 1 year of the diagnosis of HD. The authors conclude that HIV infection alters the clinical course of HD, that advanced or high-grade HD in HIV-infected individuals should be considered indicative of AIDS, and all patients with HD should be tested for HIV.     

Fine-needle aspiration cytology of Hodgkin disease: a study of 89 cases with emphasis on false-negative cases

INTRODUCTION. Although the cytologic features of Hodgkin disease (HD) has been well described, HD accounts for most of the false-negative fine-needle aspiration (FNA) biopsies of malignant lymphomas. In this study, the authors examined the factors contributing to a false-negative diagnosis of HD. METHODS: Eighty-nine cases from 72 patients (23 females and 49 males) with HD evaluated by FNA were identified between 1990 and 1999. The patients' ages ranged from 5 to 90 years (median, 38 years). Eighty-five FNAs were from lymph nodes, and 4 were from extranodal sites. Histologic correlation was available for all patients. RESULTS: Based on the original cytologic diagnosis, 43 (48.3%) cases had a positive diagnosis of HD, 20 (22.5%) suspicious or atypical diagnosis, 13 (14.6%) a benign diagnosis (false-negative cases), and 10 (11.2%) were nondiagnostic. Three (3.4%) additional cases had a malignant diagnosis other than HD. After review, three false-negative cases were reclassified as HD and seven as atypical lymphoid proliferation. Three of these 10 cases also showed conspicuous collections of histiocytes mimicking poorly formed granulomas. In those "atypical" cases, only rare Reed-Sternberg (R-S) cells variants were identified. No R-S cells or its variants were identified in the remaining three false-negative cases; subsequent excisional biopsy showed partial involvement of the lymph node by HD in two cases. Among the nondiagnostic cases, nine cases showed considerable fibrosis in the resected lymph node. In addition, six cases were performed without on-site assessment. CONCLUSIONS: The cytologic diagnosis of HD can be challenging when classic R-S cells are absent. Contributing factors for a false-negative diagnosis include obscuring reactive inflammatory cells, fibrosis of the involved lymph nodes, partial involvement of the lymph node by HD, sampling error, and misinterpretation. On-site assessment significantly minimizes the false-negative diagnostic rate. Furthermore, additional material can be obtained for ancillary studies. Cancer (Cancer Cytopathol) Copyright 2001 American Cancer Society.     

Second malignancies after treatment for Hodgkin's disease

The occurrence of treatment-related second malignancy following Hodgkin's disease (HD) has now been recognized as a major problem. The purpose of this study was to review our experience with second malignancies in patients treated for Hodgkin's disease, comparing the results with the international literature data. Six hundred and sixty five patients with HD were treated in our department, between 1978 and 1996. Second neoplasm developed in 32 cases (4.8%). Seven secondary hematological malignancies were observed: four acute nonlymphocytic leukemias, two non-Hodgkin's lymphomas and one chronic myeloid leukemia. Among patients with second hematological malignancies, the mean age at diagnosis of HD was 44 years and the mean interval until the development of second malignancy was 6.1 years. Five patients received chemo- and radiotherapy and in two cases chemotherapy was used. Three of the seven patients are alive. Twenty-five patients have had solid tumors, affecting lung (5), breast (3), colon (3), stomach (2), urinary bladder (2), head-and-neck (1), thyroid gland (1), esophagus (1), liver (1), pancreas (1), furthermore, three sarcomas and two malignant melanomas were observed. Their mean age at the diagnosis of HD was 46 years and the mean period of latency was 8.3 years. Chemotherapy was applied to nine patients, 16 patients received both chemo- and radiotherapy. Eleven patients had solid tumors in the region irradiated earlier. Ten out of the 25 patients are alive, three patients' present state is unknown. Since alkylating agents increase the risk of leukemia and irradiation contributes mainly to other malignancies, future treatment protocols should attempt to reduce the most serious consequence of therapy without compromising the survival. It is necessary to investigate the impact of additional risk factors. Careful, lifelong observation is indicated for patients with HD, with special attention given to new clinical signs and symptoms.     

桥本氏病合并甲状腺乳头状腺癌

目的：探讨桥本氏病(HD)合并甲状腺乳头状腺癌(PTC)的发病机理、诊断和治疗。方法：回顾性分析9年间收治的HD合并PTC12例的临床资料，均行手术治疗，随访。结果：HD合并PTC的患病率为25%(12／48)术前误诊、漏诊达75％，术中快速切片确诊11例，术后病理切片确诊1例。全组病例均出现甲状腺结节，根据患者具体情况采取不同范围的甲状腺切除术，3例加行颈淋巴结清扫术。术后病理切片发现颈淋巴结转移3例，术后服用甲状腺素片。所有患者均获随访，随访时间为6个月～8年，患者预后好，无一例死亡、复发或转移。结论：HD可继发PTC。HD合并PTC诊断困难。诊断关键在于充分了解HD和PTC的临床表现，综合运用血清免疫学检查、B超、同位素扫描、细针抽吸细胞学等检查。对怀疑HD合并PTC者应予以手术治疗。术中快速病理切片大多可确诊，手术方式应个体化，术后服用甲状腺素片等。     

The clinical course of nonsmall cell lung carcinoma in survivors of Hodgkin disease

BACKGROUND: The objective of this study was to document the natural history of second lung carcinomas, common second tumors that arise in survivors of Hodgkin disease (HD). METHODS: The data bases of the Memorial Sloan-Kettering Cancer Center were searched to retrieve those patients who were listed with a diagnosis of both lung carcinoma and HD. Information was extracted regarding their HD (including age at diagnosis and treatment received) and their lung carcinoma (including smoking history, latency from HD, histology, disease stage, treatment received, treatment response, and survival). RESULTS: Twenty-one lung carcinomas were diagnosed in 19 patients, with a median latency of 13 years from the time of diagnosis of HD. Only five patients underwent complete resection, and four patients were alive and disease free at the last follow-up. In contrast, the median survival of 14 patients with unresectable disease was 3 months. No major objective responses were documented after chemotherapy. Poor performance status and prior thoracic radiotherapy limited treatment in patients with advanced disease. All patients had either received radiotherapy to the chest for HD or had a history of smoking; 74% of patients had both risk factors for the development of lung carcinoma. CONCLUSIONS: In patients with a history of HD, survival after the development of lung carcinoma is poor. Because surgical resection can lead to long-term survival, early detection is crucial. HD survivors, especially those with a history of smoking, should undergo careful surveillance for second primary lung carcinomas and other diseases. Patients who are diagnosed with HD should abstain from smoking. Physicians should assess specifically the smoking status of all HD patients and prescribe a smoking cessation program.     

Humoral hypercalcemia in Hodgkin's disease. Clinical and laboratory evaluation

To provide further understanding of humoral hypercalcemia in Hodgkin's disease (HD) the authors describe the clinical features and laboratory investigation of three patients recently treated at Massachusetts General Hospital. All were middle-aged men who presented with symptomatic hypercalcemia which led to a diagnosis of bulky intraabdominal HD. None had evidence of bone involvement or hyperparathyroidism. In the two cases tested 1,25(OH)2D3 was elevated at the time of diagnosis. These characteristics are remarkably similar to those of ten patients with HD and probable humoral hypercalcemia described in the literature. The diagnosis of HD was supported in Cases 1 and 3 by genomic blot analysis which showed no evidence of T-cell or B-cell tumor origin. In an in vitro assay, primary tumor medium from Case 1 stimulated dose-dependent bone resorption which was not entirely ascribable to 1,25(OH)2D3. The authors conclude that humoral hypercalcemia in HD predominantly affects males of middle age, that intraabdominal bulky disease is common, and that hypercalcemia appears to be mediated by tumor related production of 1,25(OH)2D3 in concert with a second factor.     

Hodgkin's disease occurring in a child after liver transplantation

Here we describe the case of a 14-year-old boy who underwent livertransplantation for post-Kasai biliary atresia when aged 4. Antirejectiontreatment consisted of prednisone and cyclosporine. At the age of 11 years thepatient developed left cervical lymphadenopathy; the biopsy showed classicalHodgkin's disease(HD) of the mixed cellularity (MC) type. Neoplastic cellsexpressed CD30 and CD15, and were negative for CD45, CD20, CD3, CD43, andCD79a. Furthermore, they carried the EBV-related products LMP1 and EBER1/2.Treatment consisted of three cycles of adriamycin, bleomycin, vinblastine andDTIC (ABVD), followed by radiotherapy (2,000 cGys) on involved fields. Atpresent, 42 months after the diagnosis of HD, the patient is still in completeremission. This is, to the best of our knowledge, the first reported case ofclassical HD following liver transplantation. The positivity of neoplasticcells for LMP1 and EBER1/2 indicates a possible role for immunosuppression inthe development of the tumor, and whether a reduction in immunosuppressionmight have influenced the course of the disease is open to question.     

Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease: an independent biological prognostic marker.

Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnosis or clinical factors, we compared the prognostic value of these parameters in an expanded group of classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of activated CTLs by immunohistochemistry, using a monoclonal antibody directed against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT, and their prognostic value was compared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentage of activated CTLs (ie > or = 15%) identified a group of patients with poor overall and progression-free survival time, even when adjusted for stage. In multivariate analysis, percentage of activated CTLs remained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or clinical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the differentiation between ALK negative ALCL and HD remains difficult.     

Establishment of a Human Monoclonal Antibody to Hanganutziu-Deicher Antigen as a Tumor-associated Carbohydrate Antigen

We have established a human-human hybridoma producing a monoclonal antibody against a tumor-associated carbohydrate-specific antigen, Hanganutziu-Deicher (HD) antigen. Human spleen lymphocytes from a patient with esophageal varices complicated with liver cirrhosis were cultured in serum-free medium and co-stimulated with both anti-human μ-chain antibodies and supernatants of concanavalin A-stimulated human spleen cell culture (ConA sup). The activated lymphocytes were subsequently primed in vitro with particulate HD3 antigen and fused with a parent hybrid myeloma cell line, KR-12. A hybridoma, 1F43E31G7 produced anti-HD human monoclonal antibody (IgM λ). This monoclonal antibody reacted strongly with N-glycolyl-neuraminyl α2-3 lactosylceramide (HD3) and slightly with N-glycolylneuraminyl α2-3 lactoneotetraosylceramide (HD3), but did not react with N-glycolylneuraminyl α2-3 lactoneohexaosylceramide (HD7), N-acetylneuraminyl α2-3 lactosylceramide (GM3) and other derivatives of HD3 prepared by chemical modification of the sialic acid residue of HD3, which indicates that the monoclonal antibody is directed precisely toward the terminal sialic acid and whole structure of HD3.     

Establishment of a human monoclonal antibody to Hanganutziu-Deicher antigen as a tumor-associated carbohydrate antigen

We have established a human-human hybridoma producing a monoclonal antibody against a tumor-associated carbohydrate-specific antigen, Hanganutziu-Deicher (HD) antigen. Human spleen lymphocytes from a patient with esophageal varices complicated with liver cirrhosis were cultured in serum-free medium and co-stimulated with both anti-human mu-chain antibodies and supernatants of concanavalin A-stimulated human spleen cell culture (ConA sup). The activated lymphocytes were subsequently primed in vitro with particulate HD3 antigen and fused with a parent hybrid myeloma cell line, KR-12. A hybridoma, 1F43E31G7 produced anti-HD human monoclonal antibody (IgM lambda). This monoclonal antibody reacted strongly with N-glycolylneuraminyl alpha 2-3 lactosylceramide (HD3) and slightly with N-glycolylneuraminyl alpha 2-3 lactoneotetraosylceramide (HD5), but did not react with N-glycolylneuraminyl alpha 2-3 lactoneohexaosylceramide (HD7), N-acetylneuraminyl alpha 2-3 lactosylceramide (GM3) and other derivatives of HD3 prepared by chemical modification of the sialic acid residue of HD3, which indicates that the monoclonal antibody is directed precisely toward the terminal sialic acid and whole structure of HD3.     

Delivering Chemotherapy to a Metastatic Poor Risk Testicular Cancer Patient on Hemodialysis

A standard curative intent approach of chemotherapy treatment for metastatic testicular cancer has been well established. However, there is little guidance for patients undergoing hemodialysis (HD) who require chemotherapy for this disease. Thus, we describe our treatment approach and rationale for a patient on HD with poor risk metastatic nonseminomatous germ cell tumor involving the testicle, lymph nodes, liver, and bone. After orchiectomy, five cycles of cisplatin and modified dose etoposide were delivered and strategically timed with HD. Treatment was complicated by significant neuropathy. Surgical resection of two liver lesions was performed after chemotherapy. Ten years post-chemotherapy, he remains free of clinical, biochemical, or radiological recurrence. While our patient remains free of disease after this treatment, the optimal chemotherapy and dialysis dose and schedule to maximize cure and minimize toxicity remains unknown.     

The Pathology of Hodgkin's Disease: What's New?

From the viewpoint of the pathologist, there are three major issues concerning Hodgkin's disease (HD) that must be addressed. First is making the correct diagnosis; second is identifying any pathological features that may be of prognostic importance; and third is defining the identity of the neoplastic cell. Since Hodgkin's disease (HD) was first described, the origin of the Reed-Sternberg cell and the pathogenesis of HD have remained elusive. Recently developed techniques have allowed investigators to analyze the immunophenotype and genotype of Reed-Sternberg cells. The results of these studies include recognition that, in many cases, Reed-Sternberg cells are of lymphoid origin. Thus, although in most cases of HD the diagnosis is straightforward on routinely stained sections, the conceptual dividing line between HD and non-Hodgkin's lymphoma is not as sharp as it once seemed. Occasionally, there is difficulty in distinguishing between HD and non-Hodgkin's lymphoma. Nevertheless, fundamental differences in the clinical features, histology, immunophenotype, and genotype between non-Hodgkin's lymphoma and HD remain. The impact of histological features on prognosis are controversial, largely because of the excellent prognosis of most cases of HD.     

Non-Hodgkin's lymphoma involving the uterine cervix after treatment for Hodgkin disease

The occurrence of second malignancies is an important late event following the treatment of Hodgkin's disease (HD). Occurrence of a non-Hodgkin's lymphoma (NHL) involving the uterine cervix after treatment for HD has not been previously reported. We describe a rare case of a 34-year old woman, with NHL involving the uterine cervix 7.5 years after treatment for HD. The follow-up of patients treated for HD should also include regular gynecological evaluation. In cases of abnormal findings, accurate diagnosis can only be made histologically.     

Epstein-Barr virus and survival after Hodgkin disease in a population-based series of women

BACKGROUND: Epstein-Barr virus (EBV) positive Hodgkin disease (HD), as defined by the presence of EBV genes or gene products in the malignant cells, differs epidemiologically from EBV negative HD. However, survival patterns for EBV-defined HD have not been well studied. To determine if EBV status influenced survival time after HD, the authors investigated a large, population-based series of female patients. METHODS: For 311 female patients living in the Greater San Francisco Bay Area who were aged 19-79 years with HD diagnosed between mid-1988 and 1994, histopathologically rereviewed archived biopsy specimens were assayed for EBV with immunohistochemistry and in situ hybridization. The 53 subjects with EBV positive and the 258 with EBV negative HD were observed for vital status through 1998; overall survival was analyzed with Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Epstein-Barr virus positive HD patients were older, received diagnosis at a later stage, and were less likely to have nodular sclerosis histology than EBV negative patients. Deaths were reported for 21 (40%) EBV positive and 37 (14%) EBV negative patients. No survival differences were observed between EBV positive and negative women aged 19-44 years, but survival was significantly poorer in women aged 45-79 years with EBV positive HD. Regression analysis confirmed this strong negative effect of EBV positive status on survival (hazard ratio for death, 3.0; 95% confidence interval, 1.5-6.2) as unrelated to age, stage at diagnosis, or tumor histology. CONCLUSIONS: This study found a marked survival disadvantage for EBV positive HD in older but not young adult women. These findings suggest influences of both EBV status and age on HD survival, as well as pathogenesis.     

Breast cancer in patients irradiated for Hodgkin's disease: a clinical and pathologic analysis of 45 events in 37 patients.

PURPOSE: To characterize the clinical and pathologic features of patients who developed breast cancer (BC) after treatment for Hodgkin's disease (HD). Recent epidemiologic studies have shown that women who are cured of HD have an increased risk of developing BC. PATIENTS AND METHODS: The clinical data, mammograms, and pathologic specimens of 37 women who developed 45 BCs (eight bilateral events), and had a prior history of treatment for HD were analyzed. RESULTS: The median age at diagnosis of HD was 27 years (range, 11 to 60). All patients received radiotherapy (RT) to the upper part of their body, and 10 also had chemotherapy for HD. The median interval from the treatment of HD to the diagnosis of BC was 15 years (range, 8 to 34). The median age at diagnosis of BC was 43 years (range, 27 to 75), 41% of patients were 39 years old or younger. Most mammograms (81%) showed abnormal findings of mass and/or microcalcifications. Of the eight patients (22%) with bilateral tumors, four were synchronous and four were metachronous. Involvement of the medial half of the breast occurred more frequently than in patients with primary BC (39% and 21%, respectively; P < .002). But, the histologic types, grades, presence of lymphocytic reaction, and lymphatic invasion were similar to those observed in 935 primary BC patients who were previously analyzed at our center. The 6-year actuarial relapse-free survival (RFS) for node-negative BC after HD was 85%. Node-positive patients had a significantly lower RFS of 33% (P = .002). CONCLUSIONS: In comparison to patients with primary BC, patients who develop BC after HD are more likely to be younger, have bilateral disease, and have their tumors more frequently involve the medial half of the breast. Pathologic characteristics, nodal involvement, and prognosis are similar to those of primary BC. BC in women who were treated for HD is becoming an increasing problem, as more patients cured of HD reach a follow-up time of 10 to 15 years. Breast examination and mammography at an early age should be part of the follow-up program for women who are cured of HD.