Osseous Hodgkin disease

Authors


Abstract

BACKGROUND

Hodgkin disease rarely presents as an osseous lesion, and the majority of patients are found at staging to have concurrent disease in lymph nodes. Many cases of osseous Hodgkin disease have been misdiagnosed on initial biopsy.

METHODS

All cases of Hodgkin disease diagnosed by open bone biopsy at the Mayo Clinic were identified. These included patients with primary osseous tumors, those presenting with multiple sites of involvement (with osseous lesions), and those with recurrence in bone. Recut sections were subjected to immunohistochemical stains to confirm the diagnosis. Clinical data and follow-up information were obtained from patients' charts.

RESULTS

Twenty-five patients (15 males and 10 females with an average age of 37 years) with osseous Hodgkin disease were identified during the years 1927–1996. Three patients had solitary, osseous tumors and two had primary, multifocal, osseous Hodgkin disease without involvement of nonosseous sites. Twelve patients who presented with lesions in osseous sites also had nonosseous tumors detected at staging, and 8 patients had recurrent Hodgkin disease that presented in bone. The majority of patients with primary and recurrent tumors presented only with bone pain; >50% of patients with concurrent osseous and nonosseous disease also had B-type symptoms. Nearly all lesions were in the axial and proximal appendicular skeleton. Radiographic features included osteosclerotic, osteolytic, and mixed lytic/sclerotic patterns. Cortical destruction, periosteal new bone formation, and soft tissue masses were present in 50% of cases. The histologic diagnosis of osseous Hodgkin disease occasionally was problematic; osteomyelitis was the most frequent misdiagnosis. Immunohistochemical stains revealed expression of CD15 and CD30 in neoplastic cells (which were negative for CD45 and B-cell and T-cell antigens) in all but two cases. Involved lymph nodes typically exhibited nodular sclerosis Hodgkin disease. Three patients with primary solitary osseous Hodgkin disease received radiation treatment only; at last follow-up 2 patients were alive at 22 months and 10 years, respectively. Patients with concurrent osseous and nonosseous tumors exhibited a 60% overall survival rate, but at last follow-up all 4 patients diagnosed after 1986 still were alive; those with Hodgkin disease that recurred as osseous lesions had a 60% survival rate at 8 years, but only 1 of the 5 patients diagnosed since 1984 had died of disease.

CONCLUSIONS

Osseous Hodgkin disease typically presents with bone pain, and the majority of patients have concurrent nonosseous lesions detected at staging. Radiographic features of osseous Hodgkin disease vary but indicate an aggressive malignant process. The histologic diagnosis may be problematic; immunohistochemical stains aid in establishing the diagnosis of Hodgkin disease in bone. Survival of patients with osseous Hodgkin disease has been found to be good for the last 10 years. Cancer 1999;85:1166–78. © 1999 American Cancer Society.

Lymphomas of bone are uncommon, comprising only 8% of primary malignant bone tumors.1 Most malignant lymphomas of bone are diffuse non-Hodgkin lymphomas of B-cell type.2–7 A previous study of 422 malignant lymphomas of bone included 13 cases of Hodgkin disease and no cases of primary solitary osseous Hodgkin disease.5 Although radiologically detectable osseous lesions are present in Hodgkin disease in 10–20% of cases,8–13 presentation with an osseous lesion is distinctly uncommon, with only about 20 cases reported in the literature. In most of these cases, associated lymph node involvement has been detected at staging or surgery. The histologic diagnosis of osseous Hodgkin disease is often problematic, but it is facilitated by immunohistochemical studies. We present a series of 25 cases of osseous Hodgkin disease, 17 of which presented initially as osseous lesions (including 5 primary osseous tumors), from clinical, radiologic, and pathologic perspectives.

METHODS

For this study, only patients with bone lesions biopsied at the Mayo Clinic and with medical records and slides available for review were included. Medical records were reviewed for staging, treatment, and follow-up information with approval from the Institutional Review Board of the Mayo Foundation (M.O., T.E.W.). Original slides from all lymphomas of bone were reviewed (M.O.) and those with Hodgkin disease were selected for study. All cases of osseous Hodgkin disease were reviewed by four authors (M.O., C.Y.I., J.G.S., and K.K.U.). Histologic sections were prepared from 10% formalin or B-5 fixed, paraffin embedded tissue, and stained with hematoxylin and eosin. Immunohistochemical staining was performed on recut sections using an avidin-biotin technique with diaminobenzidine, employing microwave technology for antigen retrieval.14 The antibodies used were against CD3, CD30, CD45, and L26 (DAKO, Carpinteria, CA) and CD15 (Boehringer Mannheim, Indianapolis, IN). For the diagnoses of primary osseous Hodgkin disease and primary multifocal osseous Hodgkin disease, we required that only osseous lesions be present at the time of diagnosis and staging, and for at least the following 6 months of follow-up, as in a previous study of lymphomas of bone.5

RESULTS

From representative slides of over 500 malignant lymphomas of bone, 33 cases of Hodgkin disease were found. Two cases from 1918 and 1926 were eliminated due to histologic features and immunohistochemical studies not supportive of this diagnosis. From the remaining 31 cases, 25 had medical records available for review. The skeletal distribution of the lesions and patient ages at presentation are illustrated in Figure 1. There were 38 lesions in 25 patients (15 males and 10 females; age range, 11–73 years). Twenty-seven lesions occurred in the axial skeleton; most others involved the proximal appendicular bones. Patients were subdivided into four groups, with clinical features, treatment, and follow-up data shown in Tables 1–4. Since 1980, bilateral bone marrow biopsies have been performed in staging Hodgkin disease. Radiologic studies were available for review in 16 patients with 21 lesions (Table 5). Concurrent nonosseous disease was of nodular sclerosis type in 11 of 12 classifiable cases, a slightly higher percentage of this subtype than that recently noted in Hodgkin disease overall. (Of 662 patients with Hodgkin disease who were seen at the Mayo Clinic from January 1988 through August 1997, 494 [75%] had nodular sclerosis type.)

Figure 1.

Distribution of Hodgkin disease in 25 patients by age and site of lesion (38 lesions in 25 patients). *Three cases of primary solitary osseous Hodgkin disease were present in the humerus, vertebra, and femur.

Table 1. Primary Osseous Hodgkin Disease
Case/yearAge/genderSymptomsBone siteTreatmentStatus
  1. Chemo: chemotherapy; DOD: dead of disease; AWD: alive without evidence of diseaase; LTFU: lost to follow-up.

1 196073/FRight hip painRight femurRadiationMultiple recurrences (3 and 4 yrs), inguinal lymph nodes, spleen, mediastinum, thoracic and lumbar spine, pelvic bones; treated with chemo, DOD (4 yrs)
2 196834/MLeft distal arm painLeft humerusRadiationAWD (10 yrs), then LTFU
3 199561/FLeft thoracolumbar painT11Resection and radiationAWD (22 mos)
Table 2. Primary Multifocal Osseous Hodgkin Disease
Case/yearAge/genderSymptomsBone sitesTreatmentStatus
  1. LTFU: lost to follow-up; DOD: dead of disease.

1 192742/MRight flank pain, pain in abdomen, shouldersT4–T8RadiationAlive (10 mos), then LTFU
2 195853/MLeft shoulder painLeft humerus, left iliumRadiationDOD (4 mos)
Table 3. Hodgkin Disease Presenting Simultaneously in Osseous and Nonosseous Sites
CaseYearAge/genderSigns and symptomsBone site(s)Other site(s)TreatmentStatus
  • Chemo: chemotherapy; AWD: alive without evidence of disease; DOD: dead of disease; LTFU: lost to follow-up.

  • a

    Site biopsied if more than one listed.

  • b

    Other sites biopsied in addition to bone site(s), all with nodular sclerosis Hodgkin disease, except Case 1, which exhibited Hodgkin disease of unclassifiable type.

1193458/MChest massManubriumAnterior chest wall soft tissuebRadiationDOD (date unknown)
2195350/MChest painSternumBilateral axillary lymph nodesRadiationDOD (9 mos)
3196730/MLeft leg pain, night sweats, feverLeft tibiaBilateral cervical lymph nodesRadiation, ChemoMultiple recurrences (9 mos–6 yrs) in ribs, right tibia, vertebrae, lung, treated with radiation and chemo; DOD (6 yrs)
4197137/FDraining sinuses right axilla, right axillary lymphadenopathy, feverRight scapulaRight axillary lymph nodesbChemoDOD (9 mos)
5198021/MBack pain, hip pain, weight loss, night sweats, feverLeft iliac crest,a right sacrumParaaortic and pancreatic lymph nodes, T3, T10, L4ChemoAWD (16 yrs)
6198332/MRight thigh pain, left supraclavicular lymphadenopathy, night sweatsRight femurLeft supraclavicular lymph node,b mediastinumChemoMultiple recurrences (diagnosed elsewhere, unknown sites), bone marrow transplant; DOD (6 yrs)
7198629/FLow back pain, feverRight acetabulum,a right humerusMediastinum, right supraclavicular lymph nodebChemoLTFU
8198641/MRib, chest painRight ribsRight chest wall, intercostal muscleChemoRecurrences in right chest wall (3 and 5 yrs); alive (5 yrs), then LTFU
9198641/MUpper back pain, night sweats, feverT10Lung,b T4, T6, L1; cervical, inguinal, paraaortic lymph nodes, spleenChemoRecurrence in left cervical lymph nodes, bone marrow transplant (2 yrs); AWD (10 yrs)
10199113/FChronic back pain, feverL1, L4aMediastinum, lungbChemoRecurrence (1 yr) in spleen and supraclavicular lymph nodes, bone marrow transplant; AWD (5 yrs)
11199351/FRight leg painRight iliumMediastinumChemoAWD (3 yrs)
12199611/MLeft leg pain, feverLeft iliumCervical lymph nodes,b mediastinum, liver, left ischium, right femurChemoAlive (1 yr) after multiple cycles of chemo with residual right paratracheal/anterior mediastinal mass; will possibly receive radiation
Table 4. Recurrent Hodgkin Disease Presenting in Osseous Sites
CaseYearAge/genderSigns and symptomsBone site(s)Original site/yearInitial treatmentTreatmentbStatusc
  • Chemo: chemotherapy; AWD: alive without evidence of disease; DOD: dead of disease; LTFU: lost to follow-up.

  • a

    Site biopsied if more than one listed.

  • b

    Treatment of osseous recurrence.

  • c

    Time is measured from date of diagnosis of osseous lesion.

1196420/MUnknownLeft sternuma and clavicleaCervical lymph node, 1962UnknownRadiationMultiple recurrences L1–L3 (2, 6, 7 yrs), all treated with chemo and radiation. DOD (7 yrs) with cryptococcal meningitis
2196550/FPain, right thighRight femurNasopharynx, 1962UnknownRadiationAWD (12 yrs), then LTFU
3196722/MSpinal cord compressionT7a–T11aCervical, axillary, inguinal lymph nodes, mediastinum, 1964Chemo and radiationChemo and radiationDOD (20 mos)
4198431/MBack painRight ilium,a L2Right scalene, paraaortic lymph nodes, liver, spleen, 1983ChemoChemo and radiationLTFU
5198546/FPain, numbness of right lower extremitiesL5, sacrum,a coccyxLeft cervical lymph nodes, 1984RadiationChemoAWD (8 yrs)
6198827/FHip painRight proximal femurCervical, supraclavicular lymph nodes, mediastinum, 1987Chemo and radiationChemo and radiationRecurrence in left femur (1 yr), bone marrow transplant (2 yrs); AWD (8 yrs)
7199021/FBack painRight proximal femur; ilium,a left ischiumMediastinum, 1988Chemo and radiationChemoWill have bone marrow transplant elsewhere; LTFU
8199136/MBack pain, leg painL2,a left femurCervical, axillary, inguinal lymph nodes, 1978Chemo and radiationChemoDOD (1 yr)
Table 5. Summary of Radiographic Features of 21 Skeletal Lesions in 15 Patients with Osseous Hodgkin Diseasea
Radiographic featuresGroup 1b n = 2Group 2c n = 14Group 3d n = 5Total
  • a

    No films were available from patients with multifocal osseous Hodgkin disease (Table 2).

  • b

    Primary osseous Hodgkin disease (Table 1).

  • c

    Simultaneous presentation of osseous and nonosseous Hodgkin disease (Table 3).

  • d

    Osseous recurrence of Hodgkin disease (Table 4).

Pattern of bone destruction
 Osteolysis2215
 Osteosclerosis0505
 Mixed (lytic and sclerotic)0639
Negative conventional X-ray0112
Periosteal reaction17311
Cortical destruction26311
Soft tissue mass26210
Pathologic fracture2013

Clinical Features

Primary Osseous Hodgkin disease

Features of three patients with primary osseous Hodgkin disease are listed in Table 1. Case 1, from 1960, had only a limited work up, with a negative chest radiograph but without bone marrow biopsies, bone survey, or lymphangiography. The erythrocyte sedimentation rate was elevated at 47 mm/hour (n = 0–22 mm/hour). Chemotherapy at that time consisted only of intravenous nitrogen mustard. In Case 2, staging included a negative lymphangiogram and bone survey. In Case 3, two nondiagnostic fine-needle aspiration biopsies were obtained, 1 and 2 months before a diagnosis of Hodgkin disease was rendered on examination of the resected vertebra. The results of bone survey, bone scan, bilateral iliac bone marrow biopsies, and computed tomography (CT) of the chest, abdomen, and pelvis were negative, and the patient was treated with 40 gray after surgery.

Primary multifocal osseous Hodgkin disease

Two patients presented with primary multifocal osseous Hodgkin disease (without nonosseous disease) (Table 2). Diagnosed in 1927 and 1958, these patients had very limited evaluations, compared with current standards. In Case 2, initial biopsies performed elsewhere, 18 months before presentation to the Mayo Clinic, were diagnosed as eosinophilic granuloma of both osseous sites.

Concurrent osseous and nonosseous Hodgkin disease

The largest group of patients in our study presented with osseous lesions but were found at staging to have nonosseous Hodgkin disease, or presented with such within 6 months of the osseous tumor diagnosis (Table 3). There were four Stage II lesions, two Stage III lesions, and six Stage IV lesions.15 Biopsies from three of these patients were initially misdiagnosed as osteomyelitis. Case 5 had biopsies that were interpreted as osteomyelitis on frozen section, but the diagnosis was amended the following day. In Case 9, a diagnosis of osteomyelitis was made initially elsewhere. After 1 year of antibiotic treatment, during which time B symptoms continued and additional lesions developed in many sites, biopsies revealed Hodgkin disease, which was treated with MOPP/ABVD (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vinblastine, dacarbazine). Case 12 was originally diagnosed as osteomyelitis of the left ilium. Two months later, cervical lymphadenopathy developed, and biopsies of these lymph nodes revealed nodular sclerosis Hodgkin disease. One patient (Case 8) presented 15 years after presentation with a diffuse large cell lymphoma of the left axillary region and scapula.

Hodgkin disease recurrent in bone

Eight patients had recurrent Hodgkin disease, which presented in osseous sites, more than 6 months after the original diagnoses of nonosseous Hodgkin lymphoma (Table 4). The original cases included two Stage I lesions, three Stage II lesions, and three Stage III lesions.15 Of those classifiable, there were four cases of nodular sclerosis and one of mixed cellularity subtype. One patient (Case 8) who initially presented with Hodgkin disease involving multiple lymph nodes developed cutaneous T-cell lymphoma and T-cell lymphoma of an axillary lymph node in 1983; an anaplastic plasmacytoma in a cervical lymph node in 1987; and recurrent Hodgkin disease, syncytial variant of nodular sclerosis, in a cervical lymph node in 1988, prior to developing recurrent Hodgkin disease in bone.

Radiologic Features

Radiographs of 15 patients were available for review; features are shown in Table 5. Studies included conventional radiography (18 lesions), CT (10 lesions), nuclear scintigraphy (9 lesions), and magnetic resonance imaging (MRI) (5 lesions). Lesions were located in the axial and proximal appendicular skeleton; two-thirds were axial. The five appendicular lesions were present in the proximal regions of long bones; two also showed epiphyseal involvement.

The radiographic features of osseous Hodgkin disease were variable, with osteolysis in 24% of cases (Figs. 2 and 3), osteosclerosis in 24% (Fig. 4), and an admixture of osteolysis and osteosclerosis in 45% (Figs. 5 and 6). Lesional margins were ill-defined, and there was frequent cortical destruction, periosteal reaction, and extension of tumor into surrounding soft tissue. Two lesions were detectable only with MRI (Fig. 7). CT was beneficial for assessing periosteal reaction and cortical destruction. Bone scans invariably showed increased activity at the sites of osseous Hodgkin disease. The radiographic differential diagnosis included primary sarcomas of bone, non-Hodgkin lymphomas and leukemia, osteomyelitis, and metastatic lesions.

Figure 2.

Anterior-posterior radiograph of the left humerus in a male age 34 years with primary osseous Hodgkin disease. There is a large, predominantly osteolytic destructive lesion in the proximal humerus with a comminuted pathologic fracture. The lesion is poorly marginated and permeative, characteristic of an infiltrative neoplasm involving the bone marrow.

Figure 3.

Primary Hodgkin disease of the T11 vertebra in a female patient age 61 years. Lateral radiograph of the thoracic spine (A) and axial computed tomography image (B) show a destructive lytic lesion of the vertebral body and left pedicle, with pathologic fracture and soft tissue mass.

Figure 4.

A female age 13 years with Hodgkin disease of L1 and L4. Lateral radiograph of the lumbar spine (A) shows subtle sclerosis of the L4 vertebral body. Sagittal T1-weighted magnetic resonance imaging (MRI) (B) (TR/TE, 500/20 msec) with fat saturation and gadolinium enhancement shows enhancing lesions in the bodies of L1 and L4. MRI was valuable in this case for evaluating the extent of disease at L4 and for identifying the unsuspected lesion at L1.

Figure 5.

A male age 36 years with osseous recurrence of Hodgkin disease. Anterior-posterior radiograph of the left femur shows a subtle mixed lytic and sclerotic lesion in the subtrochanteric region of the femur with ill-defined margins. Subtle periosteal new bone formation is present just inferior to the lesser trochanter (curved arrow).

Figure 6.

Recurrent Hodgkin disease of the right ilium in a female patient age 21 years with a mixed lytic and sclerotic pattern. Computed tomography scan shows a large soft tissue mass involving anterior and posterior peri-ilial soft tissues and identifies spiculated periosteal new bone (arrow), which was not identified on conventional radiographs. (There is also an artefact due to a metallic object on the skin surface).

Figure 7.

A female age 27 years with recurrent Hodgkin disease of the left femur. Coronal T1-weighted magnetic resonance imaging (MRI) (A) (TR/TE, 500/20 msec) and T2-weighted MRI (B) (TR/TE 2000/60 msec) hip images show a large, infiltrative, destructive lesion completely replacing the normal bone marrow signal in the proximal third of the left femur. The signal characteristics are typical of osseous Hodgkin disease, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Conventional radiographs were negative in this case.

In our study, there were no radiographic features that distinguished between groups when cases of primary solitary osseous Hodgkin disease were compared to those with multiple sites of involvement at presentation or osseous recurrence. However, it is noteworthy that two of three pathologic fractures occurred in patients with primary solitary osseous Hodgkin disease (Table 1, Cases 2 and 3), and both of these were lytic lesions with cortical destruction and soft tissue masses. Mineralization was not detected in either bone or soft tissue components, and classic “ivory vertebrae” were not present.

Pathologic Features

Histologically, osseous Hodgkin disease was typically present as an infiltrate between intact bone trabeculae, similar to non-Hodgkin lymphoma involving bone (Fig. 8). In some cases, bone formation was noted in cortical regions or around bone trabeculae (Fig. 9), corresponding to the periosteal reactions and osteosclerosis noted on radiographs. The infiltrate consisted of lymphocytes, eosinophils, plasma cells, and histiocytes, with atypical mononuclear cells and Reed–Sternberg cells (Fig. 10). The latter were identified in every case. Fibrosis, necrosis, and acute inflammatory cells were present to varying degrees. Only 1 case (Fig. 11; Table 3, Case 6) exhibited features diagnostic of a specific subtype of Hodgkin disease (nodular sclerosis), identical to those in a left supraclavicular lymph node. Well-formed granulomata, such as those present in fungal or mycobacterial infection, or sarcoidosis, were not present in any case.

Figure 8.

Biopsy of Hodgkin disease of the right acetabulum showing a diffusely infiltrative process without destruction of trabecular bone.

Figure 9.

Reactive bone formation in osseous Hodgkin disease along (A) cortical and (B) trabecular bone surfaces.

Figure 10.

Typical osseous Hodgkin disease infiltrate with mixed, predominantly lymphocytic background (A) and Reed–Sternberg cells (B).

Figure 11.

Biopsy of the right femur. This unusual example shows destruction of bone by nodular sclerosis Hodgkin disease.

Immunohistochemical stains for CD15 and CD30 were positive in neoplastic cells (Fig. 12), with corresponding nonimmunoreactivity for B- and T-cell markers and CD45 in all but 2 cases. In one case, sufficient material was not available in paraffin blocks for additional studies. In the second, histologic features were typical of Hodgkin disease, but the atypical cells of Reed–Sternberg type lacked immunoreactivity to CD15, CD30, CD45, and B- and T-cell markers. Molecular genetic studies revealed no clonal rearrangements of immunoglobulin genes or T-cell receptor genes. In this case, Hodgkin disease was diagnosed on the basis of the histomorphologic features in conjunction with these findings.

Figure 12.

Immunohistochemical stains (A) for CD15, showing immunoreactivity of Reed–Sternberg cells with characteristic perinuclear dotlike pattern, and (B) for CD30, showing immunoreactivity of Reed–Sternberg cells in osseous Hodgkin disease.

The most frequent misdiagnosis was acute osteomyelitis. This diagnosis was suggested by large areas of necrosis with prominent polymorphonuclear cell infiltration (Fig. 13), alternating with areas of fibrosis and chronic inflammation. Reed–Sternberg cells were sparsely present, however, and immunohistochemical results were identical to those noted above. In two cases, eosinophils were very prominent (Fig. 14), but Reed–Sternberg cells were also present, and there were no Langerhans cells.

Figure 13.

Reed–Sternberg cells were sparsely present in this case of osseous Hodgkin disease, in a background of acute inflammatory cells.

Figure 14.

Reed–Sternberg cell and prominent eosinophils in osseous Hodgkin disease.

DISCUSSION

Hodgkin disease usually presents clinically with painless lymphadenopathy, most typically in the cervical region. Although radiologically detectable bone involvement is not unusual in advanced cases of Hodgkin lymphoma, osseous lesions are seldom the primary manifestations of this disease. In a previous study of 422 malignant lymphomas of bone, there were only 13 cases of Hodgkin disease,5 none of which was a primary lesion, as defined in our study. Hodgkin disease involving osseous sites must also be distinguished from involvement of the bone marrow by Hodgkin disease, which occurs in approximately 5–10% of patients.16–21 Unlike cases with bone marrow involvement, however, Hodgkin disease with clinically symptomatic osseous involvement has been associated with prognoses similar to, or slightly better than, those with lymph node disease alone.22, 23

In our study, of 17 patients who presented with osseous lesions, 3 had primary solitary osseous tumors. Four cases of primary solitary osseous Hodgkin disease have been previously reported in the English-language literature.23–26 Two were reported before 1944, however, and thus were inadequately staged by current standards.23, 24 Gold and Mirra25 reported a case of primary humeral Hodgkin disease in a woman age 25 years who survived for 4 1/2 years after receiving radiation only. The survival of their patient, and of two primary solitary cases reported herein, after only radiation to the osseous sites, attests to the true primary nature of these rare lesions.27 This point is important, because Hodgkin disease involving osseous sites has sometimes been considered to portend an unfavorable prognosis, or even to represent Stage IV disease.

Three previously reported cases of primary Hodgkin disease involving multifocal osseous sites were treated with chemotherapy, with or without radiation.28–30 As in our examples of primary multifocal osseous Hodgkin disease, 2 of these cases29, 30 had limited follow-up (less than 6 months); 1 survived without recurrence for 3 years.28

Radiographic evidence of bone involvement has been noted in 10–15% of cases of Hodgkin disease;13 these lesions are not typically biopsied. Although these lesions are distinct from those in the current study with regard to clinical presentation, Parker et al.31 reported a distribution of lesions similar to that in our study, with a predilection for the axial and proximal appendicular skeleton. Of interest, all except one of our cases presented in adults in bones containing hematopoietic marrow. Osseous Hodgkin disease presenting in the sternum, sometimes with an associated soft tissue mass, has been reported as an unusual presentation of this tumor,32–34 and three of our cases had sternal and/or manubrial involvement.

The radiologic features of osseous Hodgkin disease have been described as osteosclerotic, osteolytic, or mixed osteosclerotic/osteolytic.9, 35–37 Lytic lesions were sometimes interpreted as representative of hematogenous spread, and sclerotic lesions as direct extensions of disease from contiguous lymph nodes.16, 36 However, two of our three primary solitary cases were lytic, and the cases that presented with osseous recurrence were not distinct radiologically. Furthermore, although regional lymph nodes may be involved in cases of osseous Hodgkin disease, less than half of the cases in our study that presented with both osseous and nonosseous disease had lymph node disease that might be considered contiguous with osseous foci.

The histologic diagnosis of osseous Hodgkin disease may be very problematic, undoubtedly related to the rarity of presentation of Hodgkin disease in bone. All four cases reported by Ozdemirli et al.37 were described as diagnostic problems. Osteomyelitis is a particularly difficult differential diagnostic entity, as the clinical and radiologic features of this and osseous Hodgkin disease may be quite similar. Necrosis and extensive polymorphonuclear cell infiltration (similar to that sometimes noted in Hodgkin disease in lymph nodes) were present in two of our cases initially misdiagnosed as osteomyelitis. In these cases, the patient had concurrent lymphadenopathy, or developed such within 6 months.

The misdiagnosis of eosinophilic granuloma has been noted previously in Hodgkin disease,38, 39 and in 1 case the 15-month delay in diagnosis was stated to have resulted in the death of that patient.39 In a study by Chan et al.,40 of four adolescent patients who presented with “primary” bone lesions (all of whom had lymph node disease at diagnosis), eosinophilic granuloma was initially suspected or favored in all cases, based on histologic studies. Eosinophilic granuloma may be associated with fever, and the sites of presentation of this entity may overlap with those of osseous Hodgkin disease. Radiographically, however, eosinophilic granuloma usually shows well-delineated osteolytic lesions, a feature which is helpful in distinguishing this from osseous Hodgkin disease.

Most cases of osseous non-Hodgkin lymphoma are B-cell neoplasms with a significant large-cell component. Non-Hodgkin osseous lymphoma may be associated with fibrosis or sclerosis. In a previous study, fibrosis with spindling of cells contributed significantly to diagnostic dilemmas in 2% of lymphomas of bone.5 Fibrosis was part of the reactive background in most of our cases of osseous Hodgkin disease, but was not a prominent feature (except in the nodular sclerosis case). In a recent study,37 however, the initial diagnosis in one case was malignant fibrous histiocytoma. Thus, it appears that Hodgkin disease should be included in the differential diagnosis of osseous lesions with cellular spindling or a fibrous stromal component.

In summary, patients who present with apparent solitary osseous Hodgkin disease almost always harbor nonosseous disease that becomes manifest with staging studies. Osseous Hodgkin disease presents with bone pain; many patients have B-type symptoms. Lymph nodes typically demonstrate nodular sclerosis Hodgkin disease. The radiographic features of osseous Hodgkin disease are nonspecific but indicate a destructive malignant process with osteosclerosis and/or osteolysis. Hodgkin disease should be included in the histologic differential diagnosis of bone lesions in cases in which osteomyelitis, eosinophilic granuloma, or a lesion with cellular spindling or a fibrous component is considered. Immunohistochemical stains are very helpful in the diagnosis of osseous Hodgkin disease. Primary, solitary osseous Hodgkin disease is extremely rare; a few cases have been cured with radiation therapy. With current chemotherapeutic regimens, the long term prognosis of patients with osseous Hodgkin disease appears good. The presence of osseous lesions in Hodgkin disease, at either presentation or recurrence, should not be interpreted to imply a worse prognosis than Hodgkin disease without involvement of osseous sites.

Ancillary