From the Departments of Pathology, Pediatrics* and Orthopedics**, JIPMER, Pondicherry 605 006, India.

Correspondence to: Dr. Surendra Kumar, Associate Professor, Department of Pathology, JIPMER, Pondicherry 605 006, India. Email:  [email protected]

Manuscript Received: January 21, 2002;
Initial review completed: May 22, 2002;
Revision Accepted: September 27, 2002.

A 10-year-old male child presented with multiple lymph node swellings. A diagnosis of Hodgkins disease was made on histopathological examination. The patient developed relapse six months after his last chemotherapy as a solitary bone tumer, which is rare. Immunohistochemical evaluation helped for the correct typing of Hodgkins disease.

Key words: Bone tumor, Hodgkins disease.

A 10-year-old male child presented with multiple lymph node swellings. A diagnosis of Hodgkins disease was made on histopathological examination. The patient developed relapse six months after his last chemotherapy as a solitary bone tumer, which is rare. Immunohistochemical evaluation helped for the correct typing of Hodgkins disease.

Key words: Bone tumor, Hodgkins disease.

Hodgkins disease (HD) rarely presents as a solitary bone tumor(1). Although HD can spread to the bones in late stages causing destructive lesions, presentation with a solitary bone lesion is uncommon(2). Fewer than 20 such cases have been reported in literature and most of them were reported prior to the development of immunological markers for Hodgkins disease and T and B cell lymphoma. Immunological markers are necessary for accurate typing of the disease. We report a child previously diagnosed as Hodgkins disease and successfully treated, who later presented with solitary bone tumor in the upper part of right humerus.

A 10 year old male child presented with multiple lymph node swellings in the axillary and cervical regions. He was diagnosed as a case of Hodgkins disease (mixed cellularity type) based on histopathological examination of the cervical lymph node. His ultrasound abdomen and whole body radiographs taken at the time of initial diagnosis were unremarkable. He was staged Ann Arber II and was put on CHOP regime consisting of cyclophosphamide 750 mg/m2 (D1), adriamycin 50 mg/m2(D1), oncovin 1.4 mg/m2(D1) and prednisolone 100mg/m2(D1-5). Six such cycles were adminstered at a gap of 21 days. Though initially he appeared to respond very well to this, he returned six months after his last chemotherapy cycle with complaints of progressive swelling over the right shoulder for 3 months. Physical examination at this presentation revealed a 5 × 4 × 3 cm size hard swelling over the right shoulder fixed to the humerus. The skin over the swelling was normal. There were no enlarged lymph nodes or hepato-splenomegaly. The radiograph showed lytic lesions over the right upper humerus. A clinical diagnosis of osteosarcoma of humerus was made. The patient’s hematological profile revealed a hemoglobin of 8.5 g/dL, a total count of 10,500/cu mm and a differential count of P40L35E15M7B3. The peripheral smear showed normocytic, normochromic red blood cells and adequate platelets. The patient was subjected to fine needle aspiration cytology.

On microscopic examination the smears revealed good cellularity. There were classical binuclear and mononuclear Reed-Sternberg cells and plasma cells in lymphoid background. A few eosinophils, neutrophils and histiocytes were also seen. A diagnosis of Hodgkins disease was made and confirmed by histopathological examination subsequently. Immunohistochemical analysis revealed staining of the atypical cells for CD15 and CD30. The cells were negative for S-100, Keratin, CD-45, CD3, CD4 and CD4sRO. The tumor was excised and he was put on a BACOP regime i.e. bleomycin-5 mg/m2iv(D15, 22), adriamycin-25 mg/m2iv(D1, 8), cyclophosphamide-650 mg/m2iv(D1,8). vincristine 1.4 mg/m2iv(D1,8) and prednisolone 60 mg/m2(D15-22). Six such cycles were given at an interval of 28 days each and the site involved was irradiated along with the axilla with 1500 rads of radiation using a 4 MeV linear accelerator. The child is doing well after one year of follow up.

Approximately 3% of primary malignant bone tumors are lymphomas. Non Hodgkins lymphoma of large B cell type are the most common type of lymphomas(4). Hodgkins disease can spread to the bones in terminal stages. Bone marrow involvement is common in Hodgkins disease, but this does not usually produce bone tumors. The lesions in Hodgkins disease have been described in detail by several authors(2,5). Radiographic evidence of bone involvement is seen in about 14% of Hodgkins disease. Lytic, sclerotic or mixed bone lesions may be present in Hodgkins disease. Sometimes periosteal new bone formation is also seen(6). Multifocal bone involvement, stage IV is usually due to hematogenous dissemination(6). But sometimes direct invasion from an adjacent lymph node leads to a small solitary lesion (Stage 1E). The prognosis in stage 1E is similar to that of local nodal disease without osseous involvement.

Newcomer et al.(7) observed 24% lytic, 20% sclerotic and 15% mixed lesions in their study. The remaining 41% were unclassifiable. Granger et al(2) demonstrated 75% lytic lesions and only 5% mixed periosteal reactions. Sclerotic lesions are thought to indicate hematogenous dissemination, whereas lytic lesions may be the result of direct extension from adjacent lymph nodes(8). The most commonly involved bones are the ileum followed by vertebrae, ribs, and proximal femur(1). In the present case proximal humerus was involved which is unusual. The term primary Hodgkins disease of bone is commonly used to describe those cases presenting with osseous involvement(3,9). Many cases reported in literature had clinically detectable local or distant lymph node involvement, suggesting that true primary Hodgkins disease of the bone is quite rare.

Fig.1. Photomicrograph showing classical binucleate Read sternberg cell in lymphoid background (MGGx400).

Solitary bone lesion at the time of diagnosis is an uncommon presentation in Hodgkins disease. In our case, the boy presented with cervical and axillary lymphadenopathy and other constitutional signs and symptoms of Hodgkins disease initially, whereas later on, in relapse only solitary bone lesion was found at the right upper end of humerus. We had not come across any such case in literature who presented with solitary bone lesion during relapse, although there are a few case reports of Hodgkins disease initially presenting as solitary bone tumor.

The patient was put on chemotherapy as well as radiotherapy because patients with lymphoma of the bone especially with a previous systemic disease are better treated as for systemic disease. In a study(10) done at the Dana Farber Center on 11 children treated with radiation and chemotherapy consisting of APO (adriamycin, prednisolone and oncovin), the 8 year actuarial lymphoma free survival was 90%. There were no relapses. In the bone tumor center Bologna, Italy 23 out of 26 patients (88%) were disease free following radiation and chemotherapy (adriamycin, vincristine and cyclophosphamide) with no local relapses at 7.5 year median follow up(11). The survival of patients in Hodgkins disease of the bone receiving a combined modality treatment is around 84%. However we have found no statistics for the survival rate for patients with relapse in bone presenting as tumor.

In our case the immunohistochemical pattern was typical of Hodgkins disease (nodular sclerosis type). At the time of initial diagnosis immunocytochemistry studies were not done and the diagnosis of mixed cellularity was based on morphological picture alone. It is possible that the intial tumor was also a nodular sclerosis in its early stages, however in the absence of an initial immunocytochemistry report we can not be sure. We are of the opinion that Hodgkins disease should be considered in the differential diagnosis of solitary bone lesions particularly if radiological findings are indicative. Immunohistochemical studies are useful in the accurate typing.

The authors are grateful to Dr. Naresh of Tata Memorial Hospital, Mumbai for conducting the immunohistochemical examination of the specimen.

Contributors: SK, SF and BVB drafted the manuscript. SK conducted the pathological examination. DKP conducted the surgery and managed the patient.

Funding: None.

Competing interests: None stated.

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