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Unusual Bony Lesions of Histiocytosis X in a Patient Previously Treated for Hodgkin's Disease
Path. Res. Pract. 186,519-525 (1990)
Unusual Bony Lesions of Histiocytosis X in a Patient Previously Treated for Hodgkin's Disease
c. E. Keen, G. Philip 1, B. C. Parker2 and R. L. Souhami3
Departments of Histopathology! and Orthopaedic Surgery2, Kingston Hospital, Surrey, and the Department of Oncology, University College and Middlesex School of Medicine, London, UK
SUMMARY
We present an unusual case ofmultifocal Histiocytosis X in a 78-year-old man treated for Hodgkin's Disease 33 and 24 years previously. The Hodgkin's Disease at first involved cervical nodes and 9 years later axillary and inguinal nodes and was treated by radiotherapy. Chronic destructive lesions developed in the femora and pelvis and bone biopsies showed a curious mixture of fibroblastic tissue and foamy macrophages. These lesions eventually resulted in pathological fractures ofthe femoral necks, and bilateral hip replacements were required seven years after initial detection of the bony lesions. There was a focal infiltrate of5-100 protein positive histiocytic cells containing Birbeck granules in the femoral heads. There was radioisotopic and radiological evidence of other skeletal lesions. The association between Histiocytosis X and Hodgkin's Disease is recognised but rare and its significance is discussed.
Introduction The lesions of Histiocytosis X in bone are usually easily recognisable histologically, with a typical mix of Langerhans type histiocytes and inflammatory cells including eosinophils, making up so called eosinophilic granuloma. Occasionally in adults the pattern may be far less easily recognisable, with a mixture of fibroblastic tissue and foamy macrophages predominating 12 , and we report such a case where this much less specific pattern resulted in delay in the diagnosis. Our case is also exceptional in demonstrating chronic, destructive multifocal bone lesions decades after apparently successful treatment for Hodgkin's Disease. An association between Hodgkin's Disease and the subsequent development of symptomatic Histiocytosis X (now also known as Langerhans-cell histiocytosis 14 ) is recognised but rare. Case Report The patient presented in 1947, aged 37, with a swelling in the left side of his neck. A lymph node biopsy was © 1990 by Gustav Fischer Verlag, Stuttgart
performed and reported as Hodgkin's Disease. A chest X-ray at that time showed no evidence of lymphoma and he was treated by radiotherapy to his neck. He remained well until 1956 when he developed swellings in the right axilla and the right groin. Another node was biopsied. The histology of this node and the original biopsy were reviewed and reported as Hodgkin's Disease of the "paragranulomatous" types. He was given further radiotherapy treatment (2500 rads to both sites). In 1980, at the age of 71 years, the patient was referred to the Orthopaedic Department and was investigated for right sciatic pain which was clinically thought to be due to a degenerative lumbar disc lesion. An X-ray of the pelvis taken at that time showed an area of disorganised bone architecture of the right greater trochanter, with areas of irregular lucency and sclerosis (Fig. 1). The pelvic bones and the upper end of the left femur appeared normal. Blood investigations revealed an ESR of 94 mm in 1 hour. A biopsy was performed and large quantities of necroticlooking material were curetted from the right greater trochanter. No firm diagnosis was made on histological 0344-0338/90/0186-0519$3.50/0
520 . C. E. Keen et al.
Fig. 1. X-ray of the hips in 1980 showing the lesion in the right greater trochanter.
Fig. 2. X-ray of the hips in 1986 showing new lesions and fracture of the left neck of femur. Note that the lesion in the right greater trochanter does not appear to have progressed.
examination. The patient's sciatic pain resolved and his ESR fell to 20 mm in 1 hour. After this episode the patient remained quite well and defaulted from follow up. In 1986 he presented with a pathological fracture of the neck of the left femur. X-rays showed lesions in the left upper femur and right ilium that were not apparent in 1980, and smaller lesions were present in both lower femora and the right upper humerus. The previously noted lesion in the right trochanteric region did not appear to have progressed (Fig. 2). His fracture was fixed with a dynamic hip screw and more tissue was obtained for histology, both from the fracture site and adjacent bone but again no definite diagnosis was made from the histological material. His ESR was 98 mm in 1 hour. A technetium radioisotope scan showed increased uptake in the right humerus, both lower femora, the base of the skull and cervical vertebrae. One year later it became clear that the fracture of the neck of the left femur had not united and a total hip replacement was performed. Four months after this he sustained a pathological fracture of the right femoral neck and was treated by primary total hip
replacement. Histological examination of these specimens led to the definitive diagnosis. Low dose radiotherapy was given to his hips and thighs. He developed back pain due to pathological fractures of his lumbar vertebrae for which he received further radiotherapy, but his general condition deteriorated and he died eight years after the detection of the bony lesions. Post mortem examination was not performed. In the previous history it was noted that in 1968 an episode of thirst and polyuria was treated by a nasal hormonal spray and is presumed to have been diabetes insipidus. The symptoms from this resolved within eighteen months. In 1979 a skin lesion reported as a basal cell carcinoma was excised from his back. Pathological Findings The histology of the lymph nodes removed in 1947 and 1956 was reviewed and a diagnosis of mixed cellularity Hodgkin's Disease was confirmed (Fig. 3). The biopsy
Histiocytosis X . 521
material from the right greater trochanter in 1980 and from the region of the pathological fracture in 1986 consisted of similar yellow to orange tissue replacing bone marrow. Sections showed uniform spindle cell fibroblastic tissue (Fig. 4) replacing and enveloping pre-existing bone. There was a focal storiform growth pattern. Foamy histiocytes were prominent in many areas. A few chronic
Fig. 3. Section of the lymph node removed in 1956, showing a mixed cellular infiltrate and a Reed-Sternberg cell. H & E, x 660.
Fig. 4. Fibroblastic and xanthomatized tissue in the biopsy from the left femur in 1986. H & E, x 660.
inflammatory cells including occasional eosinophils were admixed. No acid fast bacilli, fungi or other organisms were identified by appropriate stains. Diagnoses considered at this stage included recurrent Hodgkin's Disease, low grade malignant fibrous histiocytoma and fibrous dysplasia.
522 . C. E. Keen et al.
The femoral heads removed at the time of the hip replacements in 1987 showed replacement of much of the marrow by similar yellowish tissue (Fig. 5), but small areas of paler tissue could also be seen. These areas contained a uniform population of medium sized histiocytic cells with oval, indented to folded nuclei (Fig. 6), in places admixed with lymphocytes, plasma cells and eosinophils (Fig. 7). Occasional cells were in mitosis. There was strong positive staining of cytoplasm and nuclei with polyclonal antiserum to 5-100 protein as demonstrated by an avidinbiotin immunoperoxidase technique, similar results being obtained with both decalcified and undecalcified sections. Further material was transferred to glutaraldehyde and processed for electron microscopy. In areas Birbeck granules were easily found (Fig. 8). The rest of the sections showed replacement of marrow by similar fibroblastic and xanthomatized tissue to that seen in the previous biopsy material, with smaller areas of active Histiocytosis X. The fibroblastic and xanthomatized cells were negative for 5-100 protein. There was extensive necrosis of bone and marrow in relation to the fracture sites, and within the viable lesional bone there was extensive destruction and remodelling of bone trabeculae. Discussion Eosinophilic granuloma of bone is more common in childhood than adulthood and in adults tends to be unifocal rather than multifocaP2. The destructive bony lesions in this case have been demonstrated to be due to Histiocytosis X, with active areas showing aggregation of
Langerhans type histiocytes, some of which were in mitosis, and more chronic lesions becoming fibrosed and xanthomatized in areas thus obscuring the underlying pathological process. This pattern of lesion falls within the spectrum of Histiocytosis X of bone in adults 12 but is unusual and may represent local regression3 • This fibrosing nature of the process delayed the diagnosis from 1980 to 1987. Even in retrospect it is not possible to recognise obvious diagnostic features in the earlier bone biopsy material. There are small focal accumulations of histiocytes that stain with anti-5-100 in the xanthomatized marrow in the 1986 biopsy and it is possible that if the diagnosis had been considered at that stage it could have been substantiated by that technique 4 . Alternative diagnoses included recurrent indolent Hodgkin's Disease, low grade malignant fibrous histiocytoma and fibrous dysplasia. The first possibility was suggested more on clinical than pathological grounds, although L'Hoste et aU pointed out in a discussion of possible aetiological linkage the superficial histologic resemblance between Hodgkin's Disease and Histiocytosis X which may occasionally occur. The second possibility was suggested in part by a focally prominent storiform pattern in the spindle cell fibroblastic element and the more frequent association of that condition as a second malignancy following Hodgkin's Disease. Although the age would be very unusual, the distribution of the lesions and the fibrotic and xanthomatous histology were consistent with fibrous dysplasia. A further diagnostic possibility rested on the review of the skin lesion removed in 1979. This is in fact a remarkable combined lesion consisting of a basal cell
Fig. 5. Right femoral head slice showing the yellowish
and pale tissue which has largely replaced the marrow, X 2.3.
Histiocytosis X . 523
carcinoma with an admixed and adjacent component of typical Histiocytosis X (Fig. 9). Finally, the history of possible diabetes insipidus and the area of increased radioisotope uptake in the base of the skull could have led to a consideration of the diagnosis. Three of 61 adults with Histiocytosis X of bone had involvement of the hypothalamic-pituitary axis 12 . These two possible leads to the
Fig. 6. Langerhans type histiocytes in the left femoral head. Note mitotic figure. H&E, X 560.
Fig. 7. Aggregation of Langerhans type histiocytes with admixed inflammatory cells. H & E, X 660.
diagnosis re-emphasize for the pathologist the need to avail himself of the full clinical details and to review all available histological material in cases of diagnostic difficulty. There are a few reports of cases of symptomatic Histiocytosis X following Hodgkin's Disease7- 11 , but none of these had such a long interval as the present case. Four reports 1,2,6,13 also document or mention the incidental
524 . C. E. Keen et aI.
Fig. 8. Electron mIcrograph showing Birbeck granules. Uranyl acetate and lead citrate, x 81000.
Fig. 9. Basal cell carcinoma with admixed and adjacent 5-100 positive histiocytic infiltrate. Immunoperoxidase method for 5-100 protein, X 25.
finding of Histiocytosis X in lymph nodes in a total of fourteen patients with Hodgkin's Disease and eight similar cases with non-Hodgkin's lymphoma. One case of Histiocytosis X subsequently developed Hodgkin's Disease3. The rarity of the reported association between Hodgkin's Disease and Histiocytosis X has led to the suggestion that the association is one of chance rather than an aetiological association or a complication of therapy? On the other hand, whilst the association may also occur with nonHodgkin's lymphomas, Burns et al. l point out that they have never seen Histiocytosis X in association with metastatic carcinoma in lymph nodes. Murray and Ha1l9 however, report a lytic skull lesion due to Histiocytosis X in a patient being treated for breast carcinoma, and refer to
reports of single cases in association with breast carcinoma, retinoblastoma and acute lymphoblastic leukaemia. They suggest that the paucity of reported cases in association with solid tumours other than lymphomas is due to the lack of curative salvage therapy and less thorough investigation of subsequent lesions in the majority of these patients. Neumann and Frizzera lO divide the reported cases into types according to the temporal relationship of the two conditions and suggest that while the simultaneous occurrences may be related, later occurrence of Histiocytosis X is likely to be coincidental. Objective assessment of the significance of the association of the two diseases would require population based studies of their prevalences, and we could find no such studies published. There
Histiocytosis X . 525
is a report2 of a review of 659 cases of Hodgkin's Disease yielding two examples of focal Histiocytosis X in the diagnostic node which is quoted 1 as a "crude incidence" of 0.3%. Acknowledgements We would like to thank our colleagues involved with this case including the pathologists at several hospitals without whose help the diagnosis would have been further delayed.
References 1 Burns BF, Colby TV, Dorfman RF (1983) Langerhans' cell granulomatosis (Histiocytosis X) associated with malignant lymphomas. Am J Surg Pathol 7: 529-533 2 Colby TV, Hoppe RT, Warnke RA (1981) Hodgkin's disease: A clinicopathological study of 659 cases. Cancer 49: 1848-1858 3 Frederiksen P, Thommesen P (1978) Histiocytosis X. III. Clinical value of serial biopsies. Acta Radiol Oncol 17: 362-368 4 Hall PA, O'Doherty Cj, Levison DA (1987) Langerhans cell histiocytosis: an unusual case illustrating the value of immunohistochemistry in diagnosis. Histopathology 11: 1181-1191
5 Jackson H, Parker F (1944) Hodgkin's disease. II. Pathology. New Engl J Med 231: 35-44 6Kjeldsberg CR, Kim H (1980) Eosinophilic granuloma as an incidental finding in malignant lymphoma. Arch Pathol Lab Med
104: 137-140
7 L'Hoste RJ, Arrowsmith WR, Leonard GL, McGaw H (1982) Eosinophilic granuloma occurring in a patient with Hodgkin disease. Hum Pathol 13: 592-595 8 Lyon JM, Pezzimenti J, Kranwinkel RN (1985) The development of histiocytosis X in a patient with Hodgkin's lymphoma. Conn Med 49: 354-356 9 Murray PA, Hall PA (1988) Histiocytosis X mimicking recurrent malignant disease: a report of two cases. Clin Radiol39: 310-312 10 Neumann MP, Frizzera G (1986) The coexistence of Langerhans' cell granulomatosis and malignant lymphoma may take different forms: report of seven cases with a review of the literature. Hum Pathol 17: 1060-1065 11 Sajjad SM, Luna MA (1982) Primary pulmonary histiocytosis X in two patients with Hodgkin's disease. Thorax 37: 110-113 12 Wester SM, Unni KK, Beabout JW, Dahlin DC (1982) Langerhans' cell granulomatosis (Histiocytosis X) of bone in adults. Am J Surg Pathol 6: 413-426 13 Williams JW, Dorfman RF (1979) Lymphadenopathy as the initial manifestation of histiocytosis X. Am J Surg Pathol 3: 405-421 14 Writing Group of the Histiocyte Society (1987) Histiocytosis syndromes in children. Lancet i: 208-209
Received May 25, 1989 . Accepted December 11, 1989
Key words: Bone - Hodgkin's Disease - Histiocytosis X - Basal cell carcinoma Dr. C. E. Keen, Department of Histopathology, Kingston Hospital, Surrey, KT 2 7 QB, United Kingdom
Unusual Bony Lesions of Histiocytosis X in a Patient Previously Treated for Hodgkin's Disease
c. E. Keen, G. Philip 1, B. C. Parker2 and R. L. Souhami3
Departments of Histopathology! and Orthopaedic Surgery2, Kingston Hospital, Surrey, and the Department of Oncology, University College and Middlesex School of Medicine, London, UK
SUMMARY
We present an unusual case ofmultifocal Histiocytosis X in a 78-year-old man treated for Hodgkin's Disease 33 and 24 years previously. The Hodgkin's Disease at first involved cervical nodes and 9 years later axillary and inguinal nodes and was treated by radiotherapy. Chronic destructive lesions developed in the femora and pelvis and bone biopsies showed a curious mixture of fibroblastic tissue and foamy macrophages. These lesions eventually resulted in pathological fractures ofthe femoral necks, and bilateral hip replacements were required seven years after initial detection of the bony lesions. There was a focal infiltrate of5-100 protein positive histiocytic cells containing Birbeck granules in the femoral heads. There was radioisotopic and radiological evidence of other skeletal lesions. The association between Histiocytosis X and Hodgkin's Disease is recognised but rare and its significance is discussed.
Introduction The lesions of Histiocytosis X in bone are usually easily recognisable histologically, with a typical mix of Langerhans type histiocytes and inflammatory cells including eosinophils, making up so called eosinophilic granuloma. Occasionally in adults the pattern may be far less easily recognisable, with a mixture of fibroblastic tissue and foamy macrophages predominating 12 , and we report such a case where this much less specific pattern resulted in delay in the diagnosis. Our case is also exceptional in demonstrating chronic, destructive multifocal bone lesions decades after apparently successful treatment for Hodgkin's Disease. An association between Hodgkin's Disease and the subsequent development of symptomatic Histiocytosis X (now also known as Langerhans-cell histiocytosis 14 ) is recognised but rare. Case Report The patient presented in 1947, aged 37, with a swelling in the left side of his neck. A lymph node biopsy was © 1990 by Gustav Fischer Verlag, Stuttgart
performed and reported as Hodgkin's Disease. A chest X-ray at that time showed no evidence of lymphoma and he was treated by radiotherapy to his neck. He remained well until 1956 when he developed swellings in the right axilla and the right groin. Another node was biopsied. The histology of this node and the original biopsy were reviewed and reported as Hodgkin's Disease of the "paragranulomatous" types. He was given further radiotherapy treatment (2500 rads to both sites). In 1980, at the age of 71 years, the patient was referred to the Orthopaedic Department and was investigated for right sciatic pain which was clinically thought to be due to a degenerative lumbar disc lesion. An X-ray of the pelvis taken at that time showed an area of disorganised bone architecture of the right greater trochanter, with areas of irregular lucency and sclerosis (Fig. 1). The pelvic bones and the upper end of the left femur appeared normal. Blood investigations revealed an ESR of 94 mm in 1 hour. A biopsy was performed and large quantities of necroticlooking material were curetted from the right greater trochanter. No firm diagnosis was made on histological 0344-0338/90/0186-0519$3.50/0
520 . C. E. Keen et al.
Fig. 1. X-ray of the hips in 1980 showing the lesion in the right greater trochanter.
Fig. 2. X-ray of the hips in 1986 showing new lesions and fracture of the left neck of femur. Note that the lesion in the right greater trochanter does not appear to have progressed.
examination. The patient's sciatic pain resolved and his ESR fell to 20 mm in 1 hour. After this episode the patient remained quite well and defaulted from follow up. In 1986 he presented with a pathological fracture of the neck of the left femur. X-rays showed lesions in the left upper femur and right ilium that were not apparent in 1980, and smaller lesions were present in both lower femora and the right upper humerus. The previously noted lesion in the right trochanteric region did not appear to have progressed (Fig. 2). His fracture was fixed with a dynamic hip screw and more tissue was obtained for histology, both from the fracture site and adjacent bone but again no definite diagnosis was made from the histological material. His ESR was 98 mm in 1 hour. A technetium radioisotope scan showed increased uptake in the right humerus, both lower femora, the base of the skull and cervical vertebrae. One year later it became clear that the fracture of the neck of the left femur had not united and a total hip replacement was performed. Four months after this he sustained a pathological fracture of the right femoral neck and was treated by primary total hip
replacement. Histological examination of these specimens led to the definitive diagnosis. Low dose radiotherapy was given to his hips and thighs. He developed back pain due to pathological fractures of his lumbar vertebrae for which he received further radiotherapy, but his general condition deteriorated and he died eight years after the detection of the bony lesions. Post mortem examination was not performed. In the previous history it was noted that in 1968 an episode of thirst and polyuria was treated by a nasal hormonal spray and is presumed to have been diabetes insipidus. The symptoms from this resolved within eighteen months. In 1979 a skin lesion reported as a basal cell carcinoma was excised from his back. Pathological Findings The histology of the lymph nodes removed in 1947 and 1956 was reviewed and a diagnosis of mixed cellularity Hodgkin's Disease was confirmed (Fig. 3). The biopsy
Histiocytosis X . 521
material from the right greater trochanter in 1980 and from the region of the pathological fracture in 1986 consisted of similar yellow to orange tissue replacing bone marrow. Sections showed uniform spindle cell fibroblastic tissue (Fig. 4) replacing and enveloping pre-existing bone. There was a focal storiform growth pattern. Foamy histiocytes were prominent in many areas. A few chronic
Fig. 3. Section of the lymph node removed in 1956, showing a mixed cellular infiltrate and a Reed-Sternberg cell. H & E, x 660.
Fig. 4. Fibroblastic and xanthomatized tissue in the biopsy from the left femur in 1986. H & E, x 660.
inflammatory cells including occasional eosinophils were admixed. No acid fast bacilli, fungi or other organisms were identified by appropriate stains. Diagnoses considered at this stage included recurrent Hodgkin's Disease, low grade malignant fibrous histiocytoma and fibrous dysplasia.
522 . C. E. Keen et al.
The femoral heads removed at the time of the hip replacements in 1987 showed replacement of much of the marrow by similar yellowish tissue (Fig. 5), but small areas of paler tissue could also be seen. These areas contained a uniform population of medium sized histiocytic cells with oval, indented to folded nuclei (Fig. 6), in places admixed with lymphocytes, plasma cells and eosinophils (Fig. 7). Occasional cells were in mitosis. There was strong positive staining of cytoplasm and nuclei with polyclonal antiserum to 5-100 protein as demonstrated by an avidinbiotin immunoperoxidase technique, similar results being obtained with both decalcified and undecalcified sections. Further material was transferred to glutaraldehyde and processed for electron microscopy. In areas Birbeck granules were easily found (Fig. 8). The rest of the sections showed replacement of marrow by similar fibroblastic and xanthomatized tissue to that seen in the previous biopsy material, with smaller areas of active Histiocytosis X. The fibroblastic and xanthomatized cells were negative for 5-100 protein. There was extensive necrosis of bone and marrow in relation to the fracture sites, and within the viable lesional bone there was extensive destruction and remodelling of bone trabeculae. Discussion Eosinophilic granuloma of bone is more common in childhood than adulthood and in adults tends to be unifocal rather than multifocaP2. The destructive bony lesions in this case have been demonstrated to be due to Histiocytosis X, with active areas showing aggregation of
Langerhans type histiocytes, some of which were in mitosis, and more chronic lesions becoming fibrosed and xanthomatized in areas thus obscuring the underlying pathological process. This pattern of lesion falls within the spectrum of Histiocytosis X of bone in adults 12 but is unusual and may represent local regression3 • This fibrosing nature of the process delayed the diagnosis from 1980 to 1987. Even in retrospect it is not possible to recognise obvious diagnostic features in the earlier bone biopsy material. There are small focal accumulations of histiocytes that stain with anti-5-100 in the xanthomatized marrow in the 1986 biopsy and it is possible that if the diagnosis had been considered at that stage it could have been substantiated by that technique 4 . Alternative diagnoses included recurrent indolent Hodgkin's Disease, low grade malignant fibrous histiocytoma and fibrous dysplasia. The first possibility was suggested more on clinical than pathological grounds, although L'Hoste et aU pointed out in a discussion of possible aetiological linkage the superficial histologic resemblance between Hodgkin's Disease and Histiocytosis X which may occasionally occur. The second possibility was suggested in part by a focally prominent storiform pattern in the spindle cell fibroblastic element and the more frequent association of that condition as a second malignancy following Hodgkin's Disease. Although the age would be very unusual, the distribution of the lesions and the fibrotic and xanthomatous histology were consistent with fibrous dysplasia. A further diagnostic possibility rested on the review of the skin lesion removed in 1979. This is in fact a remarkable combined lesion consisting of a basal cell
Fig. 5. Right femoral head slice showing the yellowish
and pale tissue which has largely replaced the marrow, X 2.3.
Histiocytosis X . 523
carcinoma with an admixed and adjacent component of typical Histiocytosis X (Fig. 9). Finally, the history of possible diabetes insipidus and the area of increased radioisotope uptake in the base of the skull could have led to a consideration of the diagnosis. Three of 61 adults with Histiocytosis X of bone had involvement of the hypothalamic-pituitary axis 12 . These two possible leads to the
Fig. 6. Langerhans type histiocytes in the left femoral head. Note mitotic figure. H&E, X 560.
Fig. 7. Aggregation of Langerhans type histiocytes with admixed inflammatory cells. H & E, X 660.
diagnosis re-emphasize for the pathologist the need to avail himself of the full clinical details and to review all available histological material in cases of diagnostic difficulty. There are a few reports of cases of symptomatic Histiocytosis X following Hodgkin's Disease7- 11 , but none of these had such a long interval as the present case. Four reports 1,2,6,13 also document or mention the incidental
524 . C. E. Keen et aI.
Fig. 8. Electron mIcrograph showing Birbeck granules. Uranyl acetate and lead citrate, x 81000.
Fig. 9. Basal cell carcinoma with admixed and adjacent 5-100 positive histiocytic infiltrate. Immunoperoxidase method for 5-100 protein, X 25.
finding of Histiocytosis X in lymph nodes in a total of fourteen patients with Hodgkin's Disease and eight similar cases with non-Hodgkin's lymphoma. One case of Histiocytosis X subsequently developed Hodgkin's Disease3. The rarity of the reported association between Hodgkin's Disease and Histiocytosis X has led to the suggestion that the association is one of chance rather than an aetiological association or a complication of therapy? On the other hand, whilst the association may also occur with nonHodgkin's lymphomas, Burns et al. l point out that they have never seen Histiocytosis X in association with metastatic carcinoma in lymph nodes. Murray and Ha1l9 however, report a lytic skull lesion due to Histiocytosis X in a patient being treated for breast carcinoma, and refer to
reports of single cases in association with breast carcinoma, retinoblastoma and acute lymphoblastic leukaemia. They suggest that the paucity of reported cases in association with solid tumours other than lymphomas is due to the lack of curative salvage therapy and less thorough investigation of subsequent lesions in the majority of these patients. Neumann and Frizzera lO divide the reported cases into types according to the temporal relationship of the two conditions and suggest that while the simultaneous occurrences may be related, later occurrence of Histiocytosis X is likely to be coincidental. Objective assessment of the significance of the association of the two diseases would require population based studies of their prevalences, and we could find no such studies published. There
Histiocytosis X . 525
is a report2 of a review of 659 cases of Hodgkin's Disease yielding two examples of focal Histiocytosis X in the diagnostic node which is quoted 1 as a "crude incidence" of 0.3%. Acknowledgements We would like to thank our colleagues involved with this case including the pathologists at several hospitals without whose help the diagnosis would have been further delayed.
References 1 Burns BF, Colby TV, Dorfman RF (1983) Langerhans' cell granulomatosis (Histiocytosis X) associated with malignant lymphomas. Am J Surg Pathol 7: 529-533 2 Colby TV, Hoppe RT, Warnke RA (1981) Hodgkin's disease: A clinicopathological study of 659 cases. Cancer 49: 1848-1858 3 Frederiksen P, Thommesen P (1978) Histiocytosis X. III. Clinical value of serial biopsies. Acta Radiol Oncol 17: 362-368 4 Hall PA, O'Doherty Cj, Levison DA (1987) Langerhans cell histiocytosis: an unusual case illustrating the value of immunohistochemistry in diagnosis. Histopathology 11: 1181-1191
5 Jackson H, Parker F (1944) Hodgkin's disease. II. Pathology. New Engl J Med 231: 35-44 6Kjeldsberg CR, Kim H (1980) Eosinophilic granuloma as an incidental finding in malignant lymphoma. Arch Pathol Lab Med
104: 137-140
7 L'Hoste RJ, Arrowsmith WR, Leonard GL, McGaw H (1982) Eosinophilic granuloma occurring in a patient with Hodgkin disease. Hum Pathol 13: 592-595 8 Lyon JM, Pezzimenti J, Kranwinkel RN (1985) The development of histiocytosis X in a patient with Hodgkin's lymphoma. Conn Med 49: 354-356 9 Murray PA, Hall PA (1988) Histiocytosis X mimicking recurrent malignant disease: a report of two cases. Clin Radiol39: 310-312 10 Neumann MP, Frizzera G (1986) The coexistence of Langerhans' cell granulomatosis and malignant lymphoma may take different forms: report of seven cases with a review of the literature. Hum Pathol 17: 1060-1065 11 Sajjad SM, Luna MA (1982) Primary pulmonary histiocytosis X in two patients with Hodgkin's disease. Thorax 37: 110-113 12 Wester SM, Unni KK, Beabout JW, Dahlin DC (1982) Langerhans' cell granulomatosis (Histiocytosis X) of bone in adults. Am J Surg Pathol 6: 413-426 13 Williams JW, Dorfman RF (1979) Lymphadenopathy as the initial manifestation of histiocytosis X. Am J Surg Pathol 3: 405-421 14 Writing Group of the Histiocyte Society (1987) Histiocytosis syndromes in children. Lancet i: 208-209
Received May 25, 1989 . Accepted December 11, 1989
Key words: Bone - Hodgkin's Disease - Histiocytosis X - Basal cell carcinoma Dr. C. E. Keen, Department of Histopathology, Kingston Hospital, Surrey, KT 2 7 QB, United Kingdom