Granulomatous angiitis of the spinal cord associated with Hodgkin's disease

A 28-year-old man had a 5-month history of focal and generalized neurologic symptoms culminating in a thoracic myelopathy. Evaluation revealed granulomatous angiitis of the spinal cord in association with occult nodular sclerosing Hodgkin's disease. In previous reports, manifestations indicative of intracranial involvement have dominated the clinical presentation of granulomatous angiitis associated with Hodgkin's disease. Successful therapy for Hodgkin's disease may result in marked improvement of associated granulomatous angiitis, whereas the lack or failure of therapy results in a uniformly fatal outcome. Definitive antemortem diagnosis of granulomatous angiitis requires a biopsy of involved tissue. The cause of granulomatous angiitis, as well as the nature of its association with Hodgkin's disease, remains unexplained.     

Localized isolated angiitis of the central nervous system associated with primary intracerebral lymphoma

Isolated angiitis of the central nervous system (IACNS) is a form of granulomatous vasculitis that is confined to the nervous system. A patient with localized IACNS affecting the left internal carotid and posterior cerebral artery adjacent to a primary intracerebral lymphoma of the midbrain along with associated granulomatous inflammation of the dura, leptomeninges, and ependyma of the aqueduct of Sylvius is described. His course was complicated by many neurologic complications before his death. Prednisone and cyclophosphamide were unable to control his disease. More aggressive therapy may be indicated for patients with lymphoproliferative lesions and associated central nervous system (CNS) vasculitis who fail to respond to conventional therapy.     

The association of progressive, atrophying, chronic, granulomatous dermohypodermitis with Hodgkin's disease

The case of a patient with an unusual skin disorder--progressive, atrophying, chronic, granulomatous dermohypodermitis (PACGD)--who developed Hodgkin's disease is reported. A review of the literature revealed only two other cases of PACGD, one of which affected a patient who also was found to have Hodgkin's disease. In an additional report, the diagnosis of Hodgkin's disease was made in a patient who may have had the same dermatologic disorder. The case is reported because the association of these two rare diseases is believed to be more than a chance event.     

Burkitt's Lymphoma-Leukemia in Patients Treated for Hodgkin's Disease

We reviewed all reported cases of Burkitt's lymphoma and/or Burkitt's leukemia (BLL) occurring following therapy for Hodgkin's disease. In addition to the case described in this report, a total of 19 patients have been previously reported. The male/female ratio was 3.75. Treatment for Hodgkin's disease included chemotherapy combined with radiation therapy in 15 patients, chemotherapy in 3 patients, and radiation therapy alone in 1 patient. Median interval between Hodgkin's disease and the diagnosis of BLL was 97 months. Patient characteristics are similar to those with de novo BLL. Bone marrow, abdomen, central nervous system, as well as extranodal organs were commonly involved. Typical cytogenetic translocations seen in patients with primary BLL were found in 6 patients, but 5 of these patients had additional cytogenetic abnormalities. Only 2 patients achieved complete remission after chemotherapy. The mechanism for the development of BLL after treatment for Hodgkin's disease is unknown. Although the majority of cases have been seen in patients treated with combined-modality therapy, the role of previous therapy in causing this complication cannot be assessed in this study.     

Allogeneic marrow transplantation for refractory Hodgkin's disease

Eight patients with refractory Hodgkin's disease received intensive combination chemotherapy conditioning with cyclophosphamide, carmustine (BCNU), and etoposide (VP 16-213), and allogeneic marrow transplants. All patients achieved complete responses. Three patients relapsed; two died of Hodgkin's disease and one of chronic graft-v-host disease (GVHD) and infection. In all, four patients died due to transplant-related toxicity. One patient developed a fatal B-cell lymphoproliferative disorder soon after transplantation, and died without evidence of Hodgkin's disease. One patient is alive and free of progression 29 months after transplantation. These data indicate that allogeneic marrow transplantation may be considered as therapy for selected patients with advanced Hodgkin's disease and, despite substantial toxicity, will occasionally result in long-term responses. Better patient selection would likely improve results.     

Neurologic Complications of Immune Checkpoint Inhibitors in Thoracic Malignancies

Immune checkpoint inhibitors (ICIs) have transformed the prognosis of cancers previously considered lethal. The spectrum of therapeutic indications is rapidly expanding, including the vast majority of thoracic malignancies. By enhancing the immune responses against cancer, the ICI treatments lead to the development of immune-related adverse events (irAEs) that may affect any organ. Severity varies from mild to fatal clinical manifestations. Neurologic involvement is relatively rare and highly heterogeneous, including central and peripheral nervous system diseases associated with neural-specific autoantibodies or not, central nervous system vasculitis, and granulomatous and demyelinating disorders. Symptoms often manifest within the first four cycles of treatment and can develop regardless of the class of ICI used. An unfavorable outcome is found in up to one-third of patients and is generally associated with the patients’ clinical characteristics (e.g., age, coexistence of systemic adverse events), cancer type (e.g., lung cancer versus other), and specific clinical setting (e.g., ICI treatment in patients with preexisting paraneoplastic neurologic autoimmunity, ICI rechallenge after a first neurologic irAE). Diagnosis should be suspected in patients with new-onset neurologic symptoms while on ICI treatment which are not explained by metastatic disease or other metabolic/infectious disorders. Recommended treatment is based on clinical severity and consists of ICI discontinuation with or without immunosuppressive/immunomodulatory therapy, although alternative approaches are reasonable depending on cancer status (e.g., aggressive immunosuppression without discontinuing ICI in patients with initial cancer response). Early recognition and appropriate treatment of these neurologic irAEs are crucial for improved patient outcomes and therapeutic planning.     

Hodgkin's disease presenting with isolated craniospinal involvement

A 34-year-old man presented with tumor of his cervical spinal meninges and bone and the dura over the right frontal lobe, which was shown on biopsy to be Hodgkin's lymphoma. Extensive noninvasive evaluation failed to reveal any other sites of disease. Central nervous system involvement with Hodgkin's disease is extremely rare and is almost always a late complication in patients who have widely disseminated disease in the usual nodal sites. The current patient is unique in that his initial symptoms were due to involvement of the central nervous system and he had no evidence of Hodgkin's disease elsewhere.     

Death from Hodgkin's disease after 18 years' complete remission.

Survival studies on series of patients with Hodgkin's disease have indicated that localized disease and certain histologic types are associated with a favorable prognosis. The permanency of cure in such instances has seldom been proved by long-term followup and autopsy; there is evidence that the disease may remain dormant for considerable periods, with the attendant risk of recurrence. A case is reported wherein a patient was relapse-free for 18 years prior to fatal recurrence, which was confirmed by autopsy.     

Hodgkin's disease developing in a patient with angioimmunoblastic lymphadenopathy with dysproteinemia--a case report

The case of a woman presenting the clinical and pathologic phenomena of angioimmunoblastic lymphadenopathy (AILD) with dysproteinemia is reported. The patient developed lesions in the lymph nodes, skin, lungs, liver and spleen, and her response to steroid and cyclophosphamide therapy was poor. At autopsy, microscopic findings in the mediastinal and abdominal lymph nodes were consistent with the diagnosis of Hodgkin's disease. Whereas the development of immunoblastic lymphoma is frequent in AILD, Hodgkin's disease is far less common. It is argued that malignant lymphoma in AILD may be the consequence of chronically depressed lymphocyte functions.     

Intracranial Hodgkin's disease. A report of 12 cases and review of the literature

Intracranial involvement by Hodgkin's disease is rare. Of the 30 previously reported cases, in many of which central nervous system (CNS) disease was documented postmortem, no associated risk factors have been elucidated, and response to treatment has been poor. This report cites 12 additional cases treated at the Stanford University Medical Center, five of whom have enjoyed prolonged freedom from intracranial relapse.     

Intracranial presentation of systemic Hodgkin's disease

Intracranial involvement by Hodgkin's disease is rare. We report a patient with Hodgkin's disease who had intracranial disease at presentation. We also review the literature pertaining to intracranial Hodgkin's disease. Using the key words "Hodgkin's disease" and "central nervous system (CNS) disease", we searched the Pubmed and Cancerlit databases. References were systematically reviewed and data regarding the following variables was extracted: age, gender, signs and symptoms at presentation, histology of Hodgkin's disease, cerebrospinal fluid analysis, stage and treatment. Only 36 cases of intracranial Hodgkin's disease were identified in the literature. Intracranial Hodgkin's disease at presentation is even more uncommon with only 8 reported cases. Most cases of intracranial involvement by Hodgkin's disease occur at the time of relapse. The most common presenting feature of intracranial Hodgkin's disease is a cranial nerve palsy with brain parenchyma being the most common intracranial site of involvement. Mixed cellularity histology is the most frequent subtype of Hodgkin's disease among these patients and the median survival following intracranial presentation is 46 months. Treatment has varied extensively but includes whole brain radiation with or without combination chemotherapy. Our literature review suggests that the prognosis is not dismal with appropriate treatment.     

Fusarium brain abscess: case report and literature review

Severely immunocompromised patients such as those with haematological malignancies and haematopoietic stem cell transplant recipients are at an increased risk of acquiring invasive mould infections. Fusarium, a ubiquitous fungus, can cause potentially fatal infections in such hosts. It usually manifests as skin lesions, fevers and sino‐pulmonary infections. Brain abscesses have been reported, but are relatively uncommon. We report a case of a 50‐year‐old patient with acute lymphocytic leukaemia and failed autologous peripheral stem cell transplant that presented with new onset seizures and was found to have Fusarium solani brain abscess. Nasal route was the presumed mode of entry of the fungus into the cerebrum. Treatment comprised surgical excision of the lesion, and antimycotic therapy with liposomal amphotericin B and voriconazole. Despite aggressive therapy, patient succumbed to the disease. We have provided an overview of infections secondary to Fusarium, along with a review of the central nervous system involvement by this pathogenic mould.     

Malignant lymphomas in children and adolescents

Malignant lymphomas constitute the third most common group of childhood cancers in the United States. Hodgkin's disease (HD) exhibits a bimodal age peak, with the first peak occurring in the 15-34-year age group. Nodular sclerosis is the most common histologic subtype of HD seen in children. The disease tends to be primarily supradiaphragmatic at presentation. Accurate staging is essential for determination of appropriate therapy. Staging laparotomy with splenectomy is indicated for those patients with clinically localized disease whose therapy may be altered by pathologic staging. Radiation therapy is curative in the great majority of patients with localized disease. Multimodality therapy has been employed with increasing success in patients with advanced disease. The late sequelae of therapy must be considered in the design of optimum therapeutic regimens. More than 90% of non-Hodgkin's lymphoma (NHL) in childhood can be grouped into one of three histologic subtypes: lymphoblastic, undifferentiated, and diffuse large cell type. Lymphoblastic lymphomas most commonly present with mediastinal involvement. The majority of nonlymphoblastic lymphomas arise within the abdomen. Because of the tendency of NHL for extralymphatic dissemination, systemic therapy is always required. Treatment is determined by stage and histology. Significant improvements in survival rates have resulted from the development of effective combination chemotherapy programs. Cure rates in excess of 90% can be expected in children with localized disease. The outlook for children with advanced disease of undifferentiated histology remains poor. The presence of central nervous system involvement at diagnosis is a particularly ominous sign.     

Intracardiac infections due to coagulase-negative Staphylococcus associated with Hickman catheters

Three bone marrow transplant recipients experienced right-sided intracardiac infection due to coagulase-negative Staphylococcus infection associated with Hickman catheter use. In each case, multiple blood cultures yielded coagulase-negative Staphylococcus organisms, and echocardiography demonstrated mass lesions or vegetations in the right atrium. Two patients appeared to have infected intracardiac thrombi without definite valvular involvement, whereas one had both an atrial mass and a tricuspid valve vegetation. All patients were treated with catheter removal and 4 weeks of antibiotic therapy, and one patient required cardiac surgery after failure of antibiotic therapy and an apparent paradoxic embolus to the central nervous system. Intracardiac infection is a rare but potentially fatal complication of Hickman catheter use. Echocardiography may be useful in establishing the diagnosis in suspected cases.     

Recurrent cerebral venous thrombosis revealing paraneoplastic angiitis in Hodgkin’s lymphoma

Recurrent cerebral venous thrombosis (CVT), as a manifestation of paraneoplastic angiitis and revealing of nodular lymphocyte predominant Hodgkin's disease (NLPHD), is an extremely rare condition. We herein report a 55-year-old man who developed recurrent CVT despite efficacious anticoagulant therapy and subsequent stenting of the superior longitudinal sinus. Progressive neurological deterioration ensued and a body scan revealed axillary lymph nodes. Pathological analysis led to a diagnosis of NLPHD. Conventional angiography showed CVT and multiple arterial narrowings. A paraneoplastic primary cerebral angiitis with prominent venous structure involvement was suspected. Immunotherapy using rituximab and steroids provided a dramatic recovery. This case of CVT due to paraneoplastic cerebral angiitis is a rare condition and represents a new, very rare manifestation of nodular lymphocyte predominant Hodgkin's disease.     

Paraneoplastic myelopathy at diagnosis in a patient with pathologic stage 1A Hodgkin disease.

The case of a patient with pathologic Stage 1A Hodgkin disease is reported in whom subacute paraneoplastic myelopathy developed before treatment. Myelography, computed tomography, magnetic resonance imaging, and lumbar puncture examination showed no evidence of central nervous system involvement. The patient was treated with combination chemotherapy (to avoid spinal cord exposure to radiation) without neurologic improvement. The patient's neurologic condition responded well to intrathecal dexamethasone.     

Unusual breast masses. The sequential development of mammary tuberculosis and Hodgkin's disease in a young woman

A left breast mass developed in association with pulmonary tuberculosis in a woman 26 years of age. Eight years later, rapidly fatal Hodgkin's Disease with chest wall erosion by involved mediastinal nodes simulating a breast lump developed. Subsequently, a discrete breast mass due to mammary Hodgkin's disease developed. Involvement of the breast by both tuberculosis and Hodgkin's disease, two diseases often associated with immune dysfunction, in a patient with dysmorphic features and a strong family history of tuberculosis, raises the possibility of an underlying genetic defect. This defect probably involves the immune system.     

Cryptococcosis in a cancer hospital: clinical and pathological correlates in forty-six patients.

The clinical and pathological findings in 46 patients with cryptococcosis at Memorial Sloan-Kettering Cancer Center from 1956 to 1972 are reported. The striking predilection for cryptococcal infection in patients with leukemias and lymphomas is again confirmed. Of 41 patients with neoplastic disease, those with chronic lymphatic leukemia (CLL), Hodgkin's Disease, chronic myelogenous leukemia (CML), myeloma and lymphosarcoma had the highest incidence of cryptococcosis. In all cases, neoplastic disease was widespread when infection occurred. All of these patients had leukopenia and absolute lymphopenia at the time of infection. Thirty-nine were on steroids. Thirty-one patients with neoplastic disease had disseminated infection. Review of pathology revealed a spectrum of inflammatory lesions. Histiocytic-lymphocytic infiltrates occurred in the central nervous system in 10 patients. In six cases, reaction was granulomatous. There were single instances of suppurative and fibrotic reactions. Mortality from infection was high in patients with neoplastic disease. Twenty-four of 28 deaths occurred within 60 days as a result of infection. Within one year, 10 more patients died, nine of cryptococcosis. Only three survived more than one year, and all patients died within 600 days. Twenty-nine patients with neoplastic disease received amphotericin B. Only nine survived more than 60 days.     

Factors influencing treatment recommendations in early-stage Hodgkin's disease: a survey of physicians.

BACKGROUND: The aim of this study was to explore variation in practice patterns and identify factors associated with physicians' treatment decisions for early-stage Hodgkin's disease. METHODS: We conducted a one-time mail survey of oncologists randomly selected from directories of national oncology societies (n = 207) and Hodgkin's disease experts (n = 147). The survey included questions on (i) physician factors, (ii) preferred treatment choices for six case scenarios of early-stage Hodgkin's disease that varied by patient factors, and (iii) thresholds for changing treatment recommendations. RESULTS: The response rate was 50%. For non-bulky Hodgkin's disease, 69% of respondents chose combined modality therapy (CMT). On multivariate analysis, physician factors that independently predicted for choice of CMT included a high Hodgkin's disease case load (P = 0.02) and a high percentage of patients enrolled in clinical trials (P = 0.05). Radiation oncologists had a lower threshold for adding radiation therapy (P = 0.02). More experience with second malignancy cases and longer time in practice were associated with a higher threshold for adding radiation therapy (P = 0.04 and P = 0.008, respectively). In stratified analyses, treatment decisions of non-experts were significantly influenced by physician factors, but not by patient factors. Conversely, choices of Hodgkin's disease experts were insensitive to all physician factors, but experts were significantly more likely to select chemotherapy alone in young women and CMT in older patients. CONCLUSIONS: Our results indicate that physician factors including practice type and experience may in part explain variation in practice pattern for Hodgkin's disease therapy. Hodgkin's disease experts are more likely to tailor therapy according to individual patient factors.     

Management of primary intraocular lymphoma

Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which malignant lymphoid cells invade the retina, vitreous body, or optic nerve head. It is usually a large B-cell non-Hodgkin’s lymphoma. PIOL typically presents as a vitritis that is unresponsive to corticosteroid therapy. Diagnosis of PIOL requires pathologic confirmation of malignant cells in specimens of the cerebrospinal fluid, vitreous, or chorioretinal biopsies. The optimal therapy for PIOL has yet to be determined. It is generally believed that PIOL should be treated with a combination of systemic chemotherapy, including high-dose methotrexate and radiotherapy. However, several new developments for PIOL with central nervous system involvement have been reported, including intrathecal therapy and autologous stem-cell transplantation. In addition, intravitreal methotrexate has been successful in the treatment of isolated recurrent ocular disease. This article provides an overview of treatment modalities for initial, recurrent, and relapsed PIOL.