Histopathology 1977, I, 31-37
Eosinophilic granuloma of lymph nodes
H . R E I D , H.FOX & J . S . W H I T T A K E R Departnlents of Pathology, University of Manchester and Christie Hospital, Manchester Accepted for publication 30 September 1976 REIDH., FOXH. & WHITTAKER J.S. (1977) Histopathology I, 31-37 Eosinophilic granuloma of lymph nodes Two examples are reported of eosinophilic granuloma presenting as lymphadenopathy and being apparently confined to lymph nodes. The affected nodes were characterized by a striking sinus histiocytosis, a heavy infiltration with mature eosinophils and retention of normal lymphoid follicles. The differential diagnosis of this histological picture is discussed and the prognosis considered. Keywords : lymph node, eosinophilic granuloma
Introduction
Eosinophilic granuloma of bone was described as a distinct entity by Otani & Ehrlich (1940) and Lichtenstein & Jaffe (1940). It is a benign non-neoplastic disease and the lesions may be solitary or multiple; extraosseous involvement is not of great rarity and occurs principally in the skin, oral cavity, anogenital region, lymph nodes, liver and kidney (Lichtenstein 1964). When lymph nodes are involved these are usually in the close vicinity of a skeletal lesion and it is most exceptional both for a patient with this condition to present as a lymphadenopathy and for the disease to be confined to the lymph nodes. We report here two such cases, partly because only one comparable example has been previously recorded in detail (Morgenfeld & Schajowicz 1971) and partly because the histological appearances are, though both striking and characteristic, not commonly described in standard accounts of lymph node pathology.
Case reports CASE I
A man, aged 34, presented with bilateral, painless axillary lymphadenopathy and left
3'
32
H.Reid, H.Fox and J S ,Whittaker
inguinal lymphadenopathy ;the enlarged nodes had been present for about T 2 weeks. He had no other symptoms and his previous medical history contained nothing of note. On examination no abnormal findings were noted apart from the enlarged lymph nodes in the axillae and groin. His blood count and chest X-ray were normal whilst his ESR was 29 mm/h. The left inguinal lymph nodes were excised for histological study,
Pathologicalfindings The biopsy specimen consisted of a chain of lymph nodes embedded in fat. The nodes measured up to 2 cm in diameter and were formed of firm, pinkish-grey tissue. On microscopy the basic architectural pattern of the nodes was retained but the sinuses were massively dilated and contained numerous histiocytes and eosinophils together with a sprinkling of lymphocytes and erythrocytes (Figure I). The histiocytes had vesicular nuclei, some of which had folded nuclear membranes, and pale eosinophilic cytoplasm (Figure 2); they showed no pleomorphism or atypia, did not exhibit mitotic activity and were confined to the sinuses. No phagocytic activity was seen in the histiocytes. The eosinophils were seen principally in the sinuses but were, to a lesser extent, also present in the cortical areas; within the sinuses the eosinophils were
Figure I. Case I : a markedly dilated sinus within the lymph node containing histiocytes and eosinophils. H & E. x 150. Figure 2. Case I : histiocytes in a dilated lymph node sinus. H & E.
x 450.
Figure 3. Case I : a dilated lymph node sinus containing histiocytes and diffusely distributed eosinophils. H & E. x 300. Figure 4. Case I : a dilated lymph node sinus containing histiocytes and a central ‘abscess-like’ mass of eosinophils. H & E. x 100. Figure 5. Case I : higher power view of an eosinophilic ‘abscess’in a dilated lymph node sinus. H & E. ~ 4 5 0 . Figure 6. Case I : a cortical follicle containing a germinal centre. H & E.
x 50.
34
H.Reid, H.Fox and J.S. Whittaker
diffusely distributed (Figure 3) but were also, in some areas, aggregated together in masses to form eosinophilic ‘abscesses’ (Figures 4 and 5 ) ; a quite high proportion of these aggregated masses of eosinophils showed central necrosis. A few multinucleated cells were present in the sinuses but Reed-Sternberg cells were not seen. The follicles contained small germinal centres (Figure 6). The capsule was not infiltrated by histiocytes or eosinophils. A diagnosis of eosinophilic granuloma was made. Progress
Following the histological diagnosis a skeletal survey was performed which failed to reveal any evidence of an osseous lesion. The patient was seen three months later at follow-up when his condition was unchanged. CASE 2
A man, aged 25, presented with painless lymphadenopathy of 2-3 months’ duration in
Figure 7. Case tissue. H & E.
2:
eosinophilic infiltration of the nodal capsule and perinodal fat and connective
x 120.
Figure 8. Case 2 : higher power view of eosinophilic infiltration of nodal capsule and perinodal tissue. H & E. xz50.
Eosinophilic granuloma of lymph nodes
35
the posterior triangle of the neck. There were no other symptoms and physical examination, whilst confirming the localized lymphadenopathy, revealed no other abnormality. A cervical lymph node was removed for histological examination.
Pathological findings The histological findings were very similar to those of Case I with massive infiltration of the sinuses by histiocytes and eosinophils. Eosinophil aggregates with central necrosis were again seen, but, in contrast to Case I, there was also a marked eosinophi1 infiltrate in the capsule and perinodal connective tissue (Figures 7 and 8). The histiocytes did not show any atypical features and phagocytic activity was evident in some areas; no Reed-Sternberg cells were present. Progress Following a histological diagnosis of eosinophilic granuloma a skeletal survey was performed and found to be normal. The patient was seen two months after the biopsy and the lymph node enlargement in the neck was noted to be subsiding.
Discussion The histological appearances seen in the lymph nodes of these two patients were similar to those described by Morgenfeld & Schajowicz (1971) who reported the only previously detailed documented case of eosinophilic granuloma confined to lymph nodes; they were also very similar to the findings of Lichtenstein (1953) who studied involved lymph nodes from three patients with eosinophilic granuloma of bone. The combination of striking sinus histiocytosis, a heavy infiltration with mature eosinophils and retention of normal lymphoid follicles is distinctive and not seen in any other form of lymphadenopathy. Confusion may, however, arise with other conditions associated with sinus histiocytosis or nodal eosinophilia. The absence of Reed-Sternberg cells, the retention of a normal architecture, the regularity of the histiocytes and their confinement to the sinuses help to differentiate eosinophilic granuloma from Hodgkin’s disease with marked eosinophilia whilst the appearances are quite dissimilar to those of nodal filariasis in which the eosinophils can usually be seen to be related to the presence of a worm. The absence of erythrophagocytosis and of intrahistiocytic lymphocytes, the normal nodal pattern, the presence of eosinophils and the lack of infiltrating, pleomorphic histiocytes tend to rule out malignant histiocytosis (Liao, Rosai & Daneshbod .I972), histiocytic medulIary reticulosis (Marshall 1956), sinus histiocytosis with massive lymphadenopathy (Rosai & Dorfman 1969), familial histiocytic reticulosis (Marrian & Sanerkin 1963), generalized lymphohistiocytic infiltration (Nelson, Santamaria, Olson & Nayak 1961) and familial haemophagocytic reticulosis (Farquhar & Claireaux 1952). Brucellosis, infectious mononucleosis and toxoplasmosis are readily eliminated from the differential histological diagnosis. It is not our intention to enter here into the controversy as to whether eosinophilic
36
H.Reid, H.Fox and J.S. Whittaker
granuloma is a distinct entity or simply one component of a wider histiocytic disease that includes Letterer-Siwe disease and Hand-Schuller-Christian disease-a subject that has been extensively debated without a firm conclusion having been reached. It is clear, however, that in pathological terms eosinophilic granuloma is a distinct histological entity, though one that is not confined to bone. That the lymph node lesjons described here represent an extraosseous manifestation of eosinophilic granuloma seems highly probable, for the histological features are virtually identical to those seen in the skeletal lesions of this disease and, on occasions, in the lymph nodes adjacent to such lesions. One point of note is the relatively advanced age of our two patients. Although both osseous and extraosseous eosinophilic granuloma can occur at any age, the vast majority of patients with this disease are aged less than 20 years at the time of diagnosis (Lieberman, Jones, Dargeon & Begg 1969, Schajowicz & Slullitel 1973). Although these are only the second and third documented case reports to be recorded of eosinophilic granuloma presenting as a lymphadenopathy there is reason to believe that the infrequent appearance of this lesion in the literature underestimates its true incidence, for pathologists with a special interest in lymph node disease have seen a number of unreported cases; thus Lukes (personal communication) has encountered nearly a dozen examples of this rare form of eosinophilic granuloma whilst Gowing (personal communication) has also seen a number of cases. Lieberman et al. (1969) also mention having come across a few examples of isolated nodal involvement by eosinophilic granuloma, but do not give any details. It should be noted that although this nodal lesion appears to be a true extraosseous manifestation of eosinophilic granuloma, the term is also loosely applied to lesions that do not appear to be related to this disease and which are never associated with skeletal lesions. This is certainly true of the ‘eosinophilic granuloma’ of the gastrointestinal tract (Morson & Dawson 1972) and is possibly true of the ‘eosinophilic granuloma’ that has been described in the lung (Spencer 1968). These appear to be simple nonspecific inflammatory lesions in which there is a moderately prominent eosinophilic component and lack the characteristic features of the true eosinophilic granuloma as seen in both skeletal and extraosseous lesions of this disease. The prognosis for eosinophilic granuloma presenting as lymphadenopathy and apparently being confined to lymph nodes is not well defined but the 2-year-old child with eosinophilic granuloma presenting solely with enlargement of a submaxillary node described by Morgenfeld & Schajowicz (1971) was alive and well 5 years later with no evidence of any other manifestation of the disease. Lieberman et al. (1969) believe isolated nodal involvement to be an innocuous lesion but Gowing (personal communication) considers the outlook to be variable for in most of his patients presenting in this fashion the disease has usually evolved in a chronic protracted form with the eventual development of mucosal or skeletal lesions. Lukes (personal communication) has noted that though several of his patients have subsequently developed bone lesions, the majority have not shown any evidence of extranodal extension. Both Rappaport and Ackerman (personal communications) consider that a lesion of this type may develop into a malignant histiocytosis and that it is impossible to predict the outcome with any degree of assurance.
Eosinophilic granuloma of lymph nodes
37
Acknowledgements We are particularly grateful to Professor N.F.C. Gowing (London), Dr R.J. Lukes (Los Angeles), Dr L.V. Ackerman (New York) and Dr H. Rappaport (Duarte, California) for reviewing the sections from Case I and for giving us their comments on the incidence and prognosis of this lesion. We are indebted to Mr J. Chapman and Dr R. Stone for the clinical details of these patients.
References FARQUHAR J.W. & CLAIREAUX A.E. (1952) Familial haemophagocytic reticulosis. Archives of Diseases of Childhood 27, 519-525 LIAOK.T., ROSAIJ. & DANESHBOD K. (1972) Malignant histiocytosis with cutaneous involvement and eosinophilia. American Journal of Clinical Pathology 57,438-448 LICHTENSTEIN L. (1953) Histiocytosis X. Integration of eosinophilic granuloma of bone, ‘LettererSiwe disease’ and ‘Schuller-Christian disease’ as related manifestations of a single nosologic entity. Archives of Pathology 56, 84-102 LICHTENSTEIN L. (1964) Histiocytosis X. (eosinophilic granuloma of bone, Letterer-Siwe disease and Schuller-Christian disease). Further observations of pathological and clinical importance. Journal of Bone and Joint Surgery 46A, 76-90 LICHTENSTEIN L. & JAFFEH.L. (1940) Eosinophilic granuloma of bone. With report of a case. American Journal of Pathology 16, 595-604 LIEBERMAN P.H., JONESC.R., DARGEON H.W.K. & BEGGC.F. (1969) A reappraisal of eosinophilic granuloma of bone, Hand-Schuller-Christian syndrome and Letterer-Siwe syndrome. Medicine (Baltimore) 48, 375-400 MARRIAN V.J. & SANERKIN N.G. (1963) Familial histiocytic reticulosis. Journal of ClinicalPathology 16, 65-69 MARSHALL A.H.E. ( I956) Histiocytic medullary reticulosis. Journal of Pathology and Bacteriology 71, 61-71 MORGENFELD M.D. & SCHAJOWICZ F. (1971) Solitary eosinophilic granuloma of lymph node; five year follow up. Pediatrics 48, 301-305 MORSON B.C. & DAWSON I.M.P. (1972) Gastrointestinal Pathology, pp. 281-282. Blackwell Scientific Publications, Oxford, London, Edinburgh NELSONP., SANTAMARIA A., OLSONR.L. & NAYAK N.C. (1961) Generalised lymphohistiocytic infiltration. A familial disease not previously described and different from Letterer-Siwe disease and Chediak-Higashi syndrome. Pediatrics 27, 93 1-950 OTANIS. & EHRLICH J.C. (1940) Solitary granuloma of bone simulating primary neoplasm. American Journal of Pathology 16, 479-490 ROSAIJ. & DORFMAN K.F. (1969) Sinus histiocytosis with massive lymphadenopathy. A newly recognised benign clinicopathological entity. Archives of Pathology 87, 63-70 SCHAJOWICZ F. & SLULLITEL J. (1973) Eosinophilic granuloma of bone and its relationship to Hand-Schuller-Christian and Letterer-Siwe syndromes. Journal of Bone and Joint Surgery 55% 545-565 SPENCER H. (1968) Pathology of the Lung, pp. 960-963. Pergamon Press, Oxford
Eosinophilic granuloma of lymph nodes
H . R E I D , H.FOX & J . S . W H I T T A K E R Departnlents of Pathology, University of Manchester and Christie Hospital, Manchester Accepted for publication 30 September 1976 REIDH., FOXH. & WHITTAKER J.S. (1977) Histopathology I, 31-37 Eosinophilic granuloma of lymph nodes Two examples are reported of eosinophilic granuloma presenting as lymphadenopathy and being apparently confined to lymph nodes. The affected nodes were characterized by a striking sinus histiocytosis, a heavy infiltration with mature eosinophils and retention of normal lymphoid follicles. The differential diagnosis of this histological picture is discussed and the prognosis considered. Keywords : lymph node, eosinophilic granuloma
Introduction
Eosinophilic granuloma of bone was described as a distinct entity by Otani & Ehrlich (1940) and Lichtenstein & Jaffe (1940). It is a benign non-neoplastic disease and the lesions may be solitary or multiple; extraosseous involvement is not of great rarity and occurs principally in the skin, oral cavity, anogenital region, lymph nodes, liver and kidney (Lichtenstein 1964). When lymph nodes are involved these are usually in the close vicinity of a skeletal lesion and it is most exceptional both for a patient with this condition to present as a lymphadenopathy and for the disease to be confined to the lymph nodes. We report here two such cases, partly because only one comparable example has been previously recorded in detail (Morgenfeld & Schajowicz 1971) and partly because the histological appearances are, though both striking and characteristic, not commonly described in standard accounts of lymph node pathology.
Case reports CASE I
A man, aged 34, presented with bilateral, painless axillary lymphadenopathy and left
3'
32
H.Reid, H.Fox and J S ,Whittaker
inguinal lymphadenopathy ;the enlarged nodes had been present for about T 2 weeks. He had no other symptoms and his previous medical history contained nothing of note. On examination no abnormal findings were noted apart from the enlarged lymph nodes in the axillae and groin. His blood count and chest X-ray were normal whilst his ESR was 29 mm/h. The left inguinal lymph nodes were excised for histological study,
Pathologicalfindings The biopsy specimen consisted of a chain of lymph nodes embedded in fat. The nodes measured up to 2 cm in diameter and were formed of firm, pinkish-grey tissue. On microscopy the basic architectural pattern of the nodes was retained but the sinuses were massively dilated and contained numerous histiocytes and eosinophils together with a sprinkling of lymphocytes and erythrocytes (Figure I). The histiocytes had vesicular nuclei, some of which had folded nuclear membranes, and pale eosinophilic cytoplasm (Figure 2); they showed no pleomorphism or atypia, did not exhibit mitotic activity and were confined to the sinuses. No phagocytic activity was seen in the histiocytes. The eosinophils were seen principally in the sinuses but were, to a lesser extent, also present in the cortical areas; within the sinuses the eosinophils were
Figure I. Case I : a markedly dilated sinus within the lymph node containing histiocytes and eosinophils. H & E. x 150. Figure 2. Case I : histiocytes in a dilated lymph node sinus. H & E.
x 450.
Figure 3. Case I : a dilated lymph node sinus containing histiocytes and diffusely distributed eosinophils. H & E. x 300. Figure 4. Case I : a dilated lymph node sinus containing histiocytes and a central ‘abscess-like’ mass of eosinophils. H & E. x 100. Figure 5. Case I : higher power view of an eosinophilic ‘abscess’in a dilated lymph node sinus. H & E. ~ 4 5 0 . Figure 6. Case I : a cortical follicle containing a germinal centre. H & E.
x 50.
34
H.Reid, H.Fox and J.S. Whittaker
diffusely distributed (Figure 3) but were also, in some areas, aggregated together in masses to form eosinophilic ‘abscesses’ (Figures 4 and 5 ) ; a quite high proportion of these aggregated masses of eosinophils showed central necrosis. A few multinucleated cells were present in the sinuses but Reed-Sternberg cells were not seen. The follicles contained small germinal centres (Figure 6). The capsule was not infiltrated by histiocytes or eosinophils. A diagnosis of eosinophilic granuloma was made. Progress
Following the histological diagnosis a skeletal survey was performed which failed to reveal any evidence of an osseous lesion. The patient was seen three months later at follow-up when his condition was unchanged. CASE 2
A man, aged 25, presented with painless lymphadenopathy of 2-3 months’ duration in
Figure 7. Case tissue. H & E.
2:
eosinophilic infiltration of the nodal capsule and perinodal fat and connective
x 120.
Figure 8. Case 2 : higher power view of eosinophilic infiltration of nodal capsule and perinodal tissue. H & E. xz50.
Eosinophilic granuloma of lymph nodes
35
the posterior triangle of the neck. There were no other symptoms and physical examination, whilst confirming the localized lymphadenopathy, revealed no other abnormality. A cervical lymph node was removed for histological examination.
Pathological findings The histological findings were very similar to those of Case I with massive infiltration of the sinuses by histiocytes and eosinophils. Eosinophil aggregates with central necrosis were again seen, but, in contrast to Case I, there was also a marked eosinophi1 infiltrate in the capsule and perinodal connective tissue (Figures 7 and 8). The histiocytes did not show any atypical features and phagocytic activity was evident in some areas; no Reed-Sternberg cells were present. Progress Following a histological diagnosis of eosinophilic granuloma a skeletal survey was performed and found to be normal. The patient was seen two months after the biopsy and the lymph node enlargement in the neck was noted to be subsiding.
Discussion The histological appearances seen in the lymph nodes of these two patients were similar to those described by Morgenfeld & Schajowicz (1971) who reported the only previously detailed documented case of eosinophilic granuloma confined to lymph nodes; they were also very similar to the findings of Lichtenstein (1953) who studied involved lymph nodes from three patients with eosinophilic granuloma of bone. The combination of striking sinus histiocytosis, a heavy infiltration with mature eosinophils and retention of normal lymphoid follicles is distinctive and not seen in any other form of lymphadenopathy. Confusion may, however, arise with other conditions associated with sinus histiocytosis or nodal eosinophilia. The absence of Reed-Sternberg cells, the retention of a normal architecture, the regularity of the histiocytes and their confinement to the sinuses help to differentiate eosinophilic granuloma from Hodgkin’s disease with marked eosinophilia whilst the appearances are quite dissimilar to those of nodal filariasis in which the eosinophils can usually be seen to be related to the presence of a worm. The absence of erythrophagocytosis and of intrahistiocytic lymphocytes, the normal nodal pattern, the presence of eosinophils and the lack of infiltrating, pleomorphic histiocytes tend to rule out malignant histiocytosis (Liao, Rosai & Daneshbod .I972), histiocytic medulIary reticulosis (Marshall 1956), sinus histiocytosis with massive lymphadenopathy (Rosai & Dorfman 1969), familial histiocytic reticulosis (Marrian & Sanerkin 1963), generalized lymphohistiocytic infiltration (Nelson, Santamaria, Olson & Nayak 1961) and familial haemophagocytic reticulosis (Farquhar & Claireaux 1952). Brucellosis, infectious mononucleosis and toxoplasmosis are readily eliminated from the differential histological diagnosis. It is not our intention to enter here into the controversy as to whether eosinophilic
36
H.Reid, H.Fox and J.S. Whittaker
granuloma is a distinct entity or simply one component of a wider histiocytic disease that includes Letterer-Siwe disease and Hand-Schuller-Christian disease-a subject that has been extensively debated without a firm conclusion having been reached. It is clear, however, that in pathological terms eosinophilic granuloma is a distinct histological entity, though one that is not confined to bone. That the lymph node lesjons described here represent an extraosseous manifestation of eosinophilic granuloma seems highly probable, for the histological features are virtually identical to those seen in the skeletal lesions of this disease and, on occasions, in the lymph nodes adjacent to such lesions. One point of note is the relatively advanced age of our two patients. Although both osseous and extraosseous eosinophilic granuloma can occur at any age, the vast majority of patients with this disease are aged less than 20 years at the time of diagnosis (Lieberman, Jones, Dargeon & Begg 1969, Schajowicz & Slullitel 1973). Although these are only the second and third documented case reports to be recorded of eosinophilic granuloma presenting as a lymphadenopathy there is reason to believe that the infrequent appearance of this lesion in the literature underestimates its true incidence, for pathologists with a special interest in lymph node disease have seen a number of unreported cases; thus Lukes (personal communication) has encountered nearly a dozen examples of this rare form of eosinophilic granuloma whilst Gowing (personal communication) has also seen a number of cases. Lieberman et al. (1969) also mention having come across a few examples of isolated nodal involvement by eosinophilic granuloma, but do not give any details. It should be noted that although this nodal lesion appears to be a true extraosseous manifestation of eosinophilic granuloma, the term is also loosely applied to lesions that do not appear to be related to this disease and which are never associated with skeletal lesions. This is certainly true of the ‘eosinophilic granuloma’ of the gastrointestinal tract (Morson & Dawson 1972) and is possibly true of the ‘eosinophilic granuloma’ that has been described in the lung (Spencer 1968). These appear to be simple nonspecific inflammatory lesions in which there is a moderately prominent eosinophilic component and lack the characteristic features of the true eosinophilic granuloma as seen in both skeletal and extraosseous lesions of this disease. The prognosis for eosinophilic granuloma presenting as lymphadenopathy and apparently being confined to lymph nodes is not well defined but the 2-year-old child with eosinophilic granuloma presenting solely with enlargement of a submaxillary node described by Morgenfeld & Schajowicz (1971) was alive and well 5 years later with no evidence of any other manifestation of the disease. Lieberman et al. (1969) believe isolated nodal involvement to be an innocuous lesion but Gowing (personal communication) considers the outlook to be variable for in most of his patients presenting in this fashion the disease has usually evolved in a chronic protracted form with the eventual development of mucosal or skeletal lesions. Lukes (personal communication) has noted that though several of his patients have subsequently developed bone lesions, the majority have not shown any evidence of extranodal extension. Both Rappaport and Ackerman (personal communications) consider that a lesion of this type may develop into a malignant histiocytosis and that it is impossible to predict the outcome with any degree of assurance.
Eosinophilic granuloma of lymph nodes
37
Acknowledgements We are particularly grateful to Professor N.F.C. Gowing (London), Dr R.J. Lukes (Los Angeles), Dr L.V. Ackerman (New York) and Dr H. Rappaport (Duarte, California) for reviewing the sections from Case I and for giving us their comments on the incidence and prognosis of this lesion. We are indebted to Mr J. Chapman and Dr R. Stone for the clinical details of these patients.
References FARQUHAR J.W. & CLAIREAUX A.E. (1952) Familial haemophagocytic reticulosis. Archives of Diseases of Childhood 27, 519-525 LIAOK.T., ROSAIJ. & DANESHBOD K. (1972) Malignant histiocytosis with cutaneous involvement and eosinophilia. American Journal of Clinical Pathology 57,438-448 LICHTENSTEIN L. (1953) Histiocytosis X. Integration of eosinophilic granuloma of bone, ‘LettererSiwe disease’ and ‘Schuller-Christian disease’ as related manifestations of a single nosologic entity. Archives of Pathology 56, 84-102 LICHTENSTEIN L. (1964) Histiocytosis X. (eosinophilic granuloma of bone, Letterer-Siwe disease and Schuller-Christian disease). Further observations of pathological and clinical importance. Journal of Bone and Joint Surgery 46A, 76-90 LICHTENSTEIN L. & JAFFEH.L. (1940) Eosinophilic granuloma of bone. With report of a case. American Journal of Pathology 16, 595-604 LIEBERMAN P.H., JONESC.R., DARGEON H.W.K. & BEGGC.F. (1969) A reappraisal of eosinophilic granuloma of bone, Hand-Schuller-Christian syndrome and Letterer-Siwe syndrome. Medicine (Baltimore) 48, 375-400 MARRIAN V.J. & SANERKIN N.G. (1963) Familial histiocytic reticulosis. Journal of ClinicalPathology 16, 65-69 MARSHALL A.H.E. ( I956) Histiocytic medullary reticulosis. Journal of Pathology and Bacteriology 71, 61-71 MORGENFELD M.D. & SCHAJOWICZ F. (1971) Solitary eosinophilic granuloma of lymph node; five year follow up. Pediatrics 48, 301-305 MORSON B.C. & DAWSON I.M.P. (1972) Gastrointestinal Pathology, pp. 281-282. Blackwell Scientific Publications, Oxford, London, Edinburgh NELSONP., SANTAMARIA A., OLSONR.L. & NAYAK N.C. (1961) Generalised lymphohistiocytic infiltration. A familial disease not previously described and different from Letterer-Siwe disease and Chediak-Higashi syndrome. Pediatrics 27, 93 1-950 OTANIS. & EHRLICH J.C. (1940) Solitary granuloma of bone simulating primary neoplasm. American Journal of Pathology 16, 479-490 ROSAIJ. & DORFMAN K.F. (1969) Sinus histiocytosis with massive lymphadenopathy. A newly recognised benign clinicopathological entity. Archives of Pathology 87, 63-70 SCHAJOWICZ F. & SLULLITEL J. (1973) Eosinophilic granuloma of bone and its relationship to Hand-Schuller-Christian and Letterer-Siwe syndromes. Journal of Bone and Joint Surgery 55% 545-565 SPENCER H. (1968) Pathology of the Lung, pp. 960-963. Pergamon Press, Oxford
