Case Report
Langerhans’ Cell Histiocytosis – Case Report Sqn Ldr P Kinra*, Lt Col B Mukherjee+, Lt Col V Srinivas#, Lt Col SS Thind**, Air Cmde H Subramanya++ MJAFI 2005; 61 : 88-90 Key Words : Langerhan’s cell histiocytosis
Introduction angerhans’ cell histiocytosis is a disease of unknown cause and diverse manifestations. In 1953, Lichtenstein [1] proposed that the disease entities known as eosinophilic granuloma, Hand-Schuller-Christian disease and Letterer-Siwe disease all share a common pathologic appearance. This view was challenged by Lieberman et al [2]. They suggested that Letterer-Siwe disease is not a specific entity but may involve several pathologic processes. Evidence however, suggests that at least some examples of disseminated disease with features of Letterer-Siwe syndrome are examples of Langerhans’ cell histiocytosis [3]. It was once thought that Langerhans’ cell histiocytosis most likely represented a reactive disorder rather than a neoplastic process. More recent studies, however, have demonstrated clonality in Langerhans’ cell histiocytosis, supporting a neoplastic origin [4]. Langerhans’ cell histiocytosis affects mostly children and adolescents, involves one or many body systems or tissues such as bone, lung, hypothalamus, posterior pituitary gland, skin, lymph node, liver and various soft tissues. The clinical features of Langerhans’ cell histiocytosis depend on the extent of involvement. Ordinarily, patients with solitary disease have localized pain. Patients with disseminated disease may have lymphadenopathy, skin lesions, or diabetes insipidus. We report a case of Langerhans’ histiocytosis in a 16-year-old adolescent male.
L
Case Report A 16-year male patient reported to the OPD with a swelling skull at the left parietal region of 1-month duration (Fig 1). He gave a history of trauma at the same site 1 month back. Post trauma there was no history of loss of consciousness, vomiting or bleeding from ear or nose. Examination revealed
a 5 cm diameter swelling. No punctum was noticed. The swelling was non-tender. The overlying skin was normal. Systemic examination revealed no abnormality. Aspirate revealed approximately 7-8 ml thin blood stained fluid. Direct smears and centrifuged deposit were prepared. Radiological Findings X-ray skull AP, lateral and tangential view showed a well defined soft tissue swelling over left parietal bone overlying left parietal eminence. There was an erosion of the outer table underneath the soft tissue swelling measuring approximately 2.5 cm. Multiple well defined lytic lesions of variable size were seen in the left parietal bone and left pareito-occipital
Fig. 1 : Lateral view of patient showing a swelling on left parietal region measuring 5 cm in diameter
* Graded Specialist (Pathology), 7 Air Force Hospital, Kanpur, +Classified Specialist (Pathology), Military Hospital Agra, #Classified Specialist (Pathology & Onco Pathology), Command Hospital (Eastern Command), Kolkata, **Classified Specialist (Radiology) 167 MH, ++ Commandant, IAM, Bangalore
Received : 31.01.2003; Accepted : 08.05.2003
Langerhans’ Cell Histiocytosis
89
Fig. 2 : X-ray skull (lateral view) showing a well defined lytic lesion in the left parietal bone and left pareito-occipital region Fig. 4 : Electron micrograph showing racquet shaped bierbeck granules in the cytoplasm (arrow) (14000X)
Bierbeck granules in the cytoplasm (Fig 4). The discoid shape of granules was better appreciated in tangential cuts.
Fig. 3 : Photomicrograph of aspirate cell block showing large histocytes with prominent groove (arrow) and numerous eosinophils (arrowhead 400 x)
region (Fig. 2). The largest lesion was seen in the left parietal bone measuring 2.5 x 5 cm. The margins were not sclerosed. Sella was normal in size and contour. There were no signs of increased intracranial tension. There was no evidence of intracranial calcification. The lesion was suggestive of Histiocytosis-X on radiology. Microscopy Smears showed aggregates and sheets of histiocytes with some lying separately. The histiocytes exhibited nuclear folding, coffee bean grooving and multinucleation. Scattered giant cells were seen (Fig. 3). Many cells had voluminous bubbly cytoplasm. RBC, lymphocytes, polymorphs and several eosinophils were seen in the background. No cytophagy, epithelioid cells, filarial worm or necrosis was seen. No mitotic figures were seen. Final opinion given was: Histiocytic proliferative lesion. Suggestive of Langerhans’ cell histiocytosis (Histiocytosis X). Electron Microscopy Electron microscopy showed typical racquet shaped MJAFI, Vol. 61, No. 1, 2005
Discussion Langerhans’ cell histiocytosis is a proliferative disorder of Langerhans’ cells, but its nature whether reactive, benign or malignant is still controversial. The differential diagnosis includes osteomyelitis on one hand and malignant lymphoma on the other. Rarely special stains may help in separating an unusual form of osteomyelitis from Langerhans’ cell histiocytosis. Langerhans’ cell histiocytosis cells are usually positive for S-100 protein. However, the most specific marker of Langerhans’ cell histiocytosis is CD1a. CD1a expression can be detected in frozen or in paraffinembedded tissue by use of the monoclonal antibody O10 [5]. In malignant lymphoma, the characteristic nuclear features of Langerhans’ cell histiocytosis are absent. Some authors have suggested that histologic features correlate with prognosis in Langerhans’ cell histiocytosis [6]. Contrarily, several studies suggest that the stage of the disease is much more important than the histologic appearance in predicting prognosis in Langerhans’ cell histiocytosis [7]. Kilpatrick et al [8] in a large series on Langerhans’ cell histiocytosis of bone, found hepatosplenomegaly, thrombocytopenia, young age at diagnosis, and polyostotic occurrence (three bones or more) to be associated with a poor prognosis. The radiographic features are usually quite characteristic. In the skull, Langerhans’ cell histiocytosis is manifested by areas of lucency that has a hole-inhole appearance because of the different rates of destruction of the two tables of the bone. In long bones,
90
lucent areas are frequent, with pronounced benignappearing reactive new bone formation. References 1. Lichtenstein L. histiocytosis X: Integration of Eosinophilic granulomas of bone, “Letterer-Siwe disease,” and “Schuller Christian Disease” as related manifestations of single nosologic entity. Arch Pathol 1953;56:84-102.
Das and Kashyap 1994;331:154-60. 5. Emile JF, Wechsler J, Brousse N. Langerhans’ cell histiocytosis. Definitive diagnosis with use of monoclonal antibody O10 on routine paraffin embedded samples. Am J Surg Pathol 1995;19:636-41. 6. Newton WA Jr, Hamoudi AB. Histiocytosis: a histological classification with clinical correlation. Perspect Pediatr Pathol 1973;1:251-83.
2. Liberman PH, Jones CR, Dargeon HW, Begg CF. A reappraisal of eosinophilic granulomas of bone, Hand Schuller Christian syndrome and Letter Siwe syndrome. Medicine (Baltimore) 1969;48:375-400.
7. Risdall RJ, Dehner LP, Durray P, Kobrinsky N, Robinson L, Nesbit ME Jr. Histiocytosis X (Langerhans’ cell histiocytosis). Prognostic role of histopathology. Arch Pathol Lab Med 1983;107:59-63.
3. Novice FM, Collision DW, Kleinsmith DM, Osband ME, Burdakin JH, Coskey RJ. Letterer Siwe disease in adults. Cancer 1989;63:166-74.
8. Kilpatrick SE, Wenger DE, Gilchrist GS, Shives TC, Wollan PC, Unni KK. Langerhans’ cell histiocytosis of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer 1995’76:2471-84.
4. William CL, Busque L, Griffith BB. Langerhans’ cell histiocytosis – a clonal proliferative disease. N Engl J Med
MJAFI, Vol. 61, No. 1, 2005
Langerhans’ Cell Histiocytosis – Case Report Sqn Ldr P Kinra*, Lt Col B Mukherjee+, Lt Col V Srinivas#, Lt Col SS Thind**, Air Cmde H Subramanya++ MJAFI 2005; 61 : 88-90 Key Words : Langerhan’s cell histiocytosis
Introduction angerhans’ cell histiocytosis is a disease of unknown cause and diverse manifestations. In 1953, Lichtenstein [1] proposed that the disease entities known as eosinophilic granuloma, Hand-Schuller-Christian disease and Letterer-Siwe disease all share a common pathologic appearance. This view was challenged by Lieberman et al [2]. They suggested that Letterer-Siwe disease is not a specific entity but may involve several pathologic processes. Evidence however, suggests that at least some examples of disseminated disease with features of Letterer-Siwe syndrome are examples of Langerhans’ cell histiocytosis [3]. It was once thought that Langerhans’ cell histiocytosis most likely represented a reactive disorder rather than a neoplastic process. More recent studies, however, have demonstrated clonality in Langerhans’ cell histiocytosis, supporting a neoplastic origin [4]. Langerhans’ cell histiocytosis affects mostly children and adolescents, involves one or many body systems or tissues such as bone, lung, hypothalamus, posterior pituitary gland, skin, lymph node, liver and various soft tissues. The clinical features of Langerhans’ cell histiocytosis depend on the extent of involvement. Ordinarily, patients with solitary disease have localized pain. Patients with disseminated disease may have lymphadenopathy, skin lesions, or diabetes insipidus. We report a case of Langerhans’ histiocytosis in a 16-year-old adolescent male.
L
Case Report A 16-year male patient reported to the OPD with a swelling skull at the left parietal region of 1-month duration (Fig 1). He gave a history of trauma at the same site 1 month back. Post trauma there was no history of loss of consciousness, vomiting or bleeding from ear or nose. Examination revealed
a 5 cm diameter swelling. No punctum was noticed. The swelling was non-tender. The overlying skin was normal. Systemic examination revealed no abnormality. Aspirate revealed approximately 7-8 ml thin blood stained fluid. Direct smears and centrifuged deposit were prepared. Radiological Findings X-ray skull AP, lateral and tangential view showed a well defined soft tissue swelling over left parietal bone overlying left parietal eminence. There was an erosion of the outer table underneath the soft tissue swelling measuring approximately 2.5 cm. Multiple well defined lytic lesions of variable size were seen in the left parietal bone and left pareito-occipital
Fig. 1 : Lateral view of patient showing a swelling on left parietal region measuring 5 cm in diameter
* Graded Specialist (Pathology), 7 Air Force Hospital, Kanpur, +Classified Specialist (Pathology), Military Hospital Agra, #Classified Specialist (Pathology & Onco Pathology), Command Hospital (Eastern Command), Kolkata, **Classified Specialist (Radiology) 167 MH, ++ Commandant, IAM, Bangalore
Received : 31.01.2003; Accepted : 08.05.2003
Langerhans’ Cell Histiocytosis
89
Fig. 2 : X-ray skull (lateral view) showing a well defined lytic lesion in the left parietal bone and left pareito-occipital region Fig. 4 : Electron micrograph showing racquet shaped bierbeck granules in the cytoplasm (arrow) (14000X)
Bierbeck granules in the cytoplasm (Fig 4). The discoid shape of granules was better appreciated in tangential cuts.
Fig. 3 : Photomicrograph of aspirate cell block showing large histocytes with prominent groove (arrow) and numerous eosinophils (arrowhead 400 x)
region (Fig. 2). The largest lesion was seen in the left parietal bone measuring 2.5 x 5 cm. The margins were not sclerosed. Sella was normal in size and contour. There were no signs of increased intracranial tension. There was no evidence of intracranial calcification. The lesion was suggestive of Histiocytosis-X on radiology. Microscopy Smears showed aggregates and sheets of histiocytes with some lying separately. The histiocytes exhibited nuclear folding, coffee bean grooving and multinucleation. Scattered giant cells were seen (Fig. 3). Many cells had voluminous bubbly cytoplasm. RBC, lymphocytes, polymorphs and several eosinophils were seen in the background. No cytophagy, epithelioid cells, filarial worm or necrosis was seen. No mitotic figures were seen. Final opinion given was: Histiocytic proliferative lesion. Suggestive of Langerhans’ cell histiocytosis (Histiocytosis X). Electron Microscopy Electron microscopy showed typical racquet shaped MJAFI, Vol. 61, No. 1, 2005
Discussion Langerhans’ cell histiocytosis is a proliferative disorder of Langerhans’ cells, but its nature whether reactive, benign or malignant is still controversial. The differential diagnosis includes osteomyelitis on one hand and malignant lymphoma on the other. Rarely special stains may help in separating an unusual form of osteomyelitis from Langerhans’ cell histiocytosis. Langerhans’ cell histiocytosis cells are usually positive for S-100 protein. However, the most specific marker of Langerhans’ cell histiocytosis is CD1a. CD1a expression can be detected in frozen or in paraffinembedded tissue by use of the monoclonal antibody O10 [5]. In malignant lymphoma, the characteristic nuclear features of Langerhans’ cell histiocytosis are absent. Some authors have suggested that histologic features correlate with prognosis in Langerhans’ cell histiocytosis [6]. Contrarily, several studies suggest that the stage of the disease is much more important than the histologic appearance in predicting prognosis in Langerhans’ cell histiocytosis [7]. Kilpatrick et al [8] in a large series on Langerhans’ cell histiocytosis of bone, found hepatosplenomegaly, thrombocytopenia, young age at diagnosis, and polyostotic occurrence (three bones or more) to be associated with a poor prognosis. The radiographic features are usually quite characteristic. In the skull, Langerhans’ cell histiocytosis is manifested by areas of lucency that has a hole-inhole appearance because of the different rates of destruction of the two tables of the bone. In long bones,
90
lucent areas are frequent, with pronounced benignappearing reactive new bone formation. References 1. Lichtenstein L. histiocytosis X: Integration of Eosinophilic granulomas of bone, “Letterer-Siwe disease,” and “Schuller Christian Disease” as related manifestations of single nosologic entity. Arch Pathol 1953;56:84-102.
Das and Kashyap 1994;331:154-60. 5. Emile JF, Wechsler J, Brousse N. Langerhans’ cell histiocytosis. Definitive diagnosis with use of monoclonal antibody O10 on routine paraffin embedded samples. Am J Surg Pathol 1995;19:636-41. 6. Newton WA Jr, Hamoudi AB. Histiocytosis: a histological classification with clinical correlation. Perspect Pediatr Pathol 1973;1:251-83.
2. Liberman PH, Jones CR, Dargeon HW, Begg CF. A reappraisal of eosinophilic granulomas of bone, Hand Schuller Christian syndrome and Letter Siwe syndrome. Medicine (Baltimore) 1969;48:375-400.
7. Risdall RJ, Dehner LP, Durray P, Kobrinsky N, Robinson L, Nesbit ME Jr. Histiocytosis X (Langerhans’ cell histiocytosis). Prognostic role of histopathology. Arch Pathol Lab Med 1983;107:59-63.
3. Novice FM, Collision DW, Kleinsmith DM, Osband ME, Burdakin JH, Coskey RJ. Letterer Siwe disease in adults. Cancer 1989;63:166-74.
8. Kilpatrick SE, Wenger DE, Gilchrist GS, Shives TC, Wollan PC, Unni KK. Langerhans’ cell histiocytosis of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer 1995’76:2471-84.
4. William CL, Busque L, Griffith BB. Langerhans’ cell histiocytosis – a clonal proliferative disease. N Engl J Med
MJAFI, Vol. 61, No. 1, 2005
