Childhood Histiocytoses: and the Dendritic System(L)

INDIAN PEDIATRICS VOLUME 35-FEBRAURY 1998

REFERENCES 1983; 20: 907-913. 1. Pickering H. Social and environmental 5. King J, Bratt D. Socio-economic dietary factors associated with diarrhea and and cultural factors associated with growth in young children: Child health in diarrheal disease in Trinidad and Tobago. urban Africa. Soc Sci Med 1985; 21: 121- J Trop Pediatr 1988; 34:104-107. 127. 6. Friej L, Wall S. Quantity and variation in 2. Henry EJ. Environmental sanitation and morbidity: THAID analysis of the occur- nutritional status in infants in rural St. rence of gastroenteritis among Ethiopian Lucia, West Indies. Trans R Soc Trop Med children. Inf J Epidem 1979; 8: 313-325. Hyg 1981; 75: 507-513. 7. World Development Report 1993, New 3. Shuval HI, Tilden RL, Perry BH, Grosse York, Oxford University Press, 1993; p RN. The effect of investment in water 222. supply and sanitation on health status: A threshold saturation theory. Bull Wld 8. Brisco J. The role of water supplies in im- Hlth Org 1981; 59: 243-248. proving health in poor countries. Am J Clin Nutr 1978; 31: 2100-2114. 4. Chakraborty AK, Das JC. Comparative study of incidence of diarrhea among 9. Khan MV. The interruption of Shigellosis children in two different environmental by hand washing. Trans R Soc Trop Med situations in Calcutta. Indian Pediatr Hyg 1982; 72:164-168.

cells of the mononuclear phagocyte system Childhood Histiocytoses: and the dendritic system(l). Each of the A Review of Twenty Two Cases histiocytoses of childhood is characterized by localized or generalized, reactive or neo- Anju Goyal plastic proliferation of cells similar if not Sudha Rani identical to one of these cell types(2). As Tejinder Singh per Writing Group of the Histiocyte Soci- Panna Choudhury* ety(3), various histiocytoses of childhood A.P. Dubey* have been classified into Class I, Class II and Class III. In case of Class I Histiocytosis, the proliferation cell is the Histiocytoses are a group of uncommon Langerhans cells(2). We present 22 cases of disorders characterized by proliferation of childhood histiocytosis diagnosed over a span of 10 years (1985-95). This is a retro- From the Department of Pathology and Pediatrics*, spective study emphasizing the clinico- Maulana Azad Medical College and Associated pathological features alongwith a brief Hospitals, New Delhi 110 002. review of literature. Reprint requests: Dr. Sudha Rani, D-3/9, Vasant Vihar, New Delhi 110 057. Subjects and Methods Manuscript received: September 4,1996; Twenty two children were diganosed as Initial review completed: October 23,1996; histiocytosis at the Lok Nayak Hospital, Revision accepted: August 22, 2997

151 BRIEF REFORTS

New Delhi, during the period 1985-1995. thrombocytopenia while 12 had pancyto- The age of these cases ranged from 3 penia. The clinical and hemotological months to 12 years. There were 14 males profile of these patients are summarized in and 8 females. Tables I, II and III. The morphological Pathological diagnosis was made on bone marrow aspiration (15 patients), fine needle aspiration cytology (8 patients), and/or tissue biopsy (16 patients). Hemograms were done in all cases. Special stains (PAS and Oil Red 0) were done whenever required. Results Of these 22 patients, 12 patients were anemic, 13 showed leucopenia, 16 had

152 INDIAN PEDIATRICS VOLUME 35-FEBRAURY 1998

features of these 22 cases were as follows: Discussion (i) Class I Langerhans cell histiocytosis-10; Of the 3 classes of histiocytosis in child- (ii) Class II Hemophago-cytic syndrome-9; hood, the 2 most often encountered forms and (iii) Class HI Malignant histiocytosis—3. are Langerhans cell histiocytosis (LCH) Langerhans cell histiocytosis: Diffuse histio- and hemophagocytic syndrome (HPS) cytic proliferation was observed in all the while malignant histiocytosis (MH) is 10 cases. Cells demonstrated abundant rare(4). In our series also, MH was least eosinophilic to foamy cytoplasm with large common. However, a series of 120 cases of vesicular nucleus. There were binucleate histiocytosis in children documented 54 and multinucleate forms as well. These cases of Class I, 9 of Class II and 47 of Class sheets of histiocytes, were seen admixed III histiocytosis(5). In our series, Langer- with polymorphs, lymphocytes, eosino- hans cell histiocytosis (LCH) was the com- philis and plasma cells. Eosinophilic infil- monest while malignant histiocytosis was trate was variable, being marked in 4 cases the least common in contrast to the above diagnosed as eosinophilic granuloma and study where almost an equal number of sparse in 4 cases of Letterer-Siwe disease. cases were seen in Class I and Class III These latter patients showed preponderant types. proliferation of histiocytes. In 2 cases, a diagnosis of Hand-Schuller-Christian disease Regarding the epidemiology of LCH, was made. All these cases of Class I very limited data is available largely be- histiocytosis showed rare mitotic figures cause of its relatively low incidence(6). and occasional histiocyte with phagocytic LCH can present at any age from newborn to elderly with a peak incidence between 1 activity (Fig. 1). and 4 years(7). It has a wide clinical spec- Hemophagocytic syndrome: These 9 cases trum and the prognosis varies according- showed marked increase in histiocytes with ly^). Traditional classification of clinical significant phagocytosis of platelets, eryth- variants of LCH has been based on patterns roid and myeloid cells (Fig. 2). Hemopoie- of organ involvement(8). Eosinophilic is sis was diminished to a variable degree characterized by uni-or multifocal bone le- and 7 cases showed decreased myelo- sions in the absence of organ involve- poiesis while 5 cases each showed decreas- ment^). All 4 cases of eosinophilic granu- ed megakaryopoiesis and erythropoiesis. loma in our study had lytic bone lesions Parasitic infestation was concomitantly (unifocal in 3 and multifocal in 1). Letterer- present in 4 cases of which 3 had associated Siwe disease on the other hand presents leishmaniasis and 1 had falciparum primarily with visceral involvement(lO). malaria. All of these 4 patients snowed The organs commonly affected are liver, pancytopenia. spleen, lymphnodes, bone, skin and/or Malignant histiocytosis: Only three cases of bone marrow(9). Involvement of the CNS is this entity were encountered. They showed seen less commonly(lO). In our series 3 of sheets of histiocytes with marked pleomor- the 4 patients with Letterer-Siwe disease phism. Highly cellular tumor masses were had hepatomegaly and 2 cases presented seen with atypical histiocytes showing high with lymphadenopathy and characteristic mitotic activity and large areas of necrosis. skin rash. Bone marrow involvement was observed in 3 subjects. The triad of multi- Few multinucleate forms were seen. Clus- ple bone lesions, exophthalmos and diabe- ters of pleomorphic cells were found to be tes insipidus constituting Hand-Schuller- rimmed by fibrosis (Fig. 3).

153 BRIEF REPORTS

Christian (1156356(9), was observed in 2 of ules by electron microscopy and/or posi- our cases. Seperation characterized by vis- tive stain for CDIa antigen by immunohis- ceral involvement has proved to be useful tochemistry(2) which could not be done in prognostically. However, distinction be- our cases. tween Letterer-Siwe and Hand-Schuller- Christian diseases is subtle and clinically ir- Clinical picture is usually very different in hemophagocytic syndrome. Clinical relevant^). manifestations of this entity relate to infil- Pressumptive diagnosis of LCH is tration of multiple organs, especially those based on light microscopic features(2). of the reticulo-endothelial system(9). Com- However, the definitive diagnosis requires mon presenting features are fever, in addition demonstration of Birbeck gran- splenomegaly, lymphadenopathy, hepato-

154 INDIAN PEDIATRICS VOLUME 35-FEBRAURY 1998

megaly and bone marrow involvement(11). wards specific treatment of infections, All nine patients of HPS in our study had broadspectrum antimicrobials, supportive all of the above features. The clinical profile care and steroids. These patients in particu- among familial and sporadic forms are lar show excellent response to steroids. similar and can be distinguished from other forms of histiocytosis(9). Skin rash and Malignant histiocytosis is quite rare in bone diseases are hardly ever seen in HPS. children. The cardinal features for distin- guishing between patients with malignant The morphological features are similar histiocytosis from other hematologic in both types of HPS, most prominent be- neoplasma is early widespread involve- ing proliferation of benign histiocytes dis- ment of multiple organs and tissues of the playing a striking degree of hemophago- reuculoendothelial system and extranodal cytosis(12). Infiltrates occur primarily in sites such as lung and skin(9). We encoun- lymphnode sinuses and medullary cords, tered 3 patients of malignant histiocytosis liver sinusoids and portal areas, splenic red who presented with fever and variable de- pulp and bone marrow. Variable degree of gree of hepatosplenomegaly and lympha- cytopenias are seen in these patients. Pres- denopathy. The involved lymphnodes ence of increased numbers of phagocytic show the characteristic findings(13). The histiocytes should precipitate an exhaus- cellular composition of the infiltrate is vari- tive search for underlying infection or ma- able but they demonstrate large atypical lignancy (9). In the present study 3 patients malignant cells with frequent mitoses had leishmaniasis and there was one pa- (Fig. 3). The degree of cytologic atypia is tient of falciparum malaria which were variable with nuclei having round, clefted, treated accordingly. Other 5 patients were lobulated or bizarre shapes and one or treated with broad spectrum antibiotics more prominent nucleoli(9). and steroids. All of these patients showed good response to treatment. Management In all such cases of histiocytosis, it is of infection associated HPS is directed to- suggested that clinical features, bone mar-

155 BRIEF REPORTS row findings and tissue biopsy features 1994; 70 (Suppl XXIII): S11-S16. (lymph node/liver/spleen/local site) must 7. Raney RB, D'Angio GJ. Langerhans cell be correlated to subtype the class of histiocytosis (Histiocytosis X): Experience histiocytosis for adequate management. at the Children's Hospital of Philadel- REFERENCES phia, 1970-84. Med Pediatr Oncol 1989; 17: 20-28. 1. Van Furth R. The nomenclature of mononuclear phagocytic cells: Proposal for a 8. Komp DM. Historical perspectives of new classification. In: Mononuclear Ph- Langerhans cell histiocytosis. Hemat agocytes, Vol. I. Ed Van Furth R Oxford, Oncol Clin North Am 1987; 1: 9-19. Blackwell Scientific, 1970; pp 1-6. 9. Lukeus JN. Langerhans cell histiocytosis. 2. Egeler RM, D'Angio GJ. Medical In: Witntrobe's Clinical Hematology, 9th Progress: Langerhans cell histiocytosis. J edn. Eds Lee GR. Bithell TC, Foerster J, Pediatr 1995; 127:1-11. Athens JW Philadelphia, Lea and Febiger, 1993; pp 1640-1649. 3. Writing Group of the Histiocytic Society: Histiocytosis syndromes in children. Lan- 10. Dehner LP. Morphologic findings in the cet 1987; 1: 208-209. Histiocytic Syndromes. Semin Oncol 1991; 18: 8-17. 4. Pritchard J, Broadbent V. Histiocytosis- An Introduction. Br J Cancer 1994; 70 11. Reiner AP, Spivak JL. Hemophagocytic (Suppl XXIII): S1-S3. histiocytosis: A report of 20 patients and a review of the literature. Medicine 1988; 5. Hathirat P. Chuansumirt A. Nitiyanant P, 67: 369-388. et al. Histiocytosis m children: Analysis of 120 cases and the bone marrow findings 12. Jaffe ES. Histiocytosis of lymphnodes: Bi in infection-induced hemophagocytic ology and differential diagnosis. Semin syndrome vs malignant histiocytosis. J Diagn Pathol 1988; 5: 376-386. Med Assoc Thai 1993; 76 (Suppl 2): 72-79. 13. Lampert IA, Catorsky D, Bergier N. Ma 6. Broadbent V, Egeler RM, Nesbit ME. lignant histiocytosis: A clinicopatholo- Langerhans Cell histiocytosis-Clinical gical study of 12 cases. Br ] Hematol 1978; and epidemiological aspects. Br J Cancer 40: 65-77.

Immunization Coverage in Bihar age level as reported by the State Govern- ment, which generated lot of controversy.

Padam Singh From the Institute for Research in Medical R.J. Yadav Statistics, Indian Council of Medical Research, Ansari Nagar, New Delhi 110 029. The National Family Health Survey Reprint requests: Dr. Padam Singh, Institute for Research in Medical Statistics, Indian Council (NFHS) in 1993 reported a low coverage of Medical Research, Ansari Nagar, level of immunization for children and New Delhi 110 029. mothers for the State of Bihar, using a properly designed random survey method- Manuscript received: September 2,1996; ology(1). This is in contrast to a high cover- Initial review completed: April 4,1997; Revision accepted: September 30, 1997