Histiocytosis-X: role of histology and S-100 protein in grading the severity of disease.
SY Sane, KH Nainaney
Department of Pathology, Seth G. S. Medical College, Parel, Bombay, Maharashtra.
S Y Sane
Department of Pathology, Seth G. S. Medical College, Parel, Bombay, Maharashtra.
Histiocytosis-X encompasses a wide clinical spectrum from a benign localised lesion to acute generalised disease with malignant behaviour. We have reviewed material from our 18 retrospective cases comparing histological features with clinical data. Degree of positivity for S-100 protein was studied by immunoperoxidase method. Our results indicate that diagnosis of histiocytosis-X necessitates histological confirmation but grading of histological criteria and S-100 positivity do not allow prediction of severity and extent of the disease.
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Sane S Y, Nainaney K H. Histiocytosis-X: role of histology and S-100 protein in grading the severity of disease. J Postgrad Med 1990;36:16-9
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Sane S Y, Nainaney K H. Histiocytosis-X: role of histology and S-100 protein in grading the severity of disease. J Postgrad Med [serial online] 1990 [cited 2021 Mar 3 ];36:16-9
Available from: https://www.jpgmonline.com/text.asp?1990/36/1/16/880
In 1953, Lichtenstein suggested that eosinophilic granuloma, Hand-SchollerChristian disease and Letterer-Siwe disease were variants of a single clinicopathological entity affecting tissue hitiocytes. He suggested the term 'Histiocytosis-X' to cover the entire spectrum of the disease. The basic lesion of histiocytosis-X is proliferation of Langerhans cells associated with pleocytic exudate. Clinically localised lesion is like an inflammatory focus while generalised multi-system involvement behaves like a malignant process. Conventional hematoxylin and eosin stained sections with appropriate clinical information gives a presumptive diagnosis of histiocytosis-X. Presence of S-100 protein differentiates Langerhans cells from the other inflammatory histiocytes. We therefore decided to study cases of histiocytosis-X in children confirmed by immunooeroxidase stain for S-100 protein. An attempt was made to grade various histological features and S-100 protein positivity to decide the usefulness of these parameters in predicting the extent of disease and prognosis.
On screening pediatric pathology records of the last seven years histiocytosis-X was found to be diagnosed on biopsy in 17 cases and on autopsy in 1 case. Histology sections were reviewed which included biopsies of various bone lesions (14 specimens), lymph node biopsies (3 specimens), liver biopsies (2 specimens) and biopsies of spleen, skin and oral mucosa (1 each). From the autopsy case, sections of liver, spleen, lymph nodes, lungs, kidneys and rib were studied. Histological features recorded for each section were a) number, arrangement, atypia and mitosis of Langerhans cells, b) eosinophils, c) multinucleated giant cells, d) necrosis, c) foamy cells, neutrophils and lymphocytes. These were graded semi-quantitatively as 0, 1 and 2.
Paraffin blocks were cut and deparaffinised sections were stained by immunoperoxidase method using antibody to S-100 protein (1 : 50 dilution). Positive results were recorded according to the number and density of brown staining Langerhans cells as grade 0, 1 and 2.
After the study of sections, clinical data was obtained. Information regarding skeletal X-rays, liver, spleen, lymph nodes, pulmonary disease and cutaneous or oral lesions was noted. Patients were categorised as having either multi-system involvement (MSI) or only bone involvement (BIO).
Of the 18 cases, 6 revealed multi-system involvement. Age of these patients ranged from new-born to 3 years. One was a female and five were male babies. Twelve cases revealed involvement of bone only. Three of these showed multi-osteotic involvement, but other systems were normal. Age of these children was between 5 and 14 years, except for 2 patients who were below the age of 3. Of 12 patients, 9 were males and 3 females.
Histological observations [Table:1] showed no significant difference in character or mitoses of Langerhans cells in either category of MSI or BIO. Arrangement of Langerhans cells in the form of sheets was often seen in MSI. There was no appreciable nuclear atypia of Langerhans cells in MSI as compared to in BIO. Immunostaining of S-100 protein was found to be strongly positive in 4 MSI cases and 6 BIO cases. Eosinophils were found to be more prominent in BIO than in MSI cases. Necrosis was seen more often in BIO cases but one case of MSI also revealed large amount of necrosis.
Histiocytosis-X, now known as Langerhans cell histiocytosis covers a wide spectrum of diseases from eosinophilic granuloma of bone with high rate of spontaneous remission to aggressive Letterer Siwe disease with multisystem involvement and malignant behaviour. The basic proliferating histiocyte in the disease is Langerfians cell associated with infiltrate of other hematogenous cells. The Writing Group of the Histiocytic Society (1987) has recently defined the criteria for diagnosis of Langerhans cell histiocytosis.
Histiocytosis-X shows pleocytic infiltrate of eosinophils, giant cells, foamy cells, histiocytes, with varying degree of necrosis and sprinkling of neutrophils and lymphocytes. The lesion appears like an inflammatory process but characteristic histiocytes i.e. Langerhans cells are diagnostic. These histiocytes are nonphagocytic with typical folded nucleus. Chromatin is finely distributed and nuclear membrane is thin. Cytoplasm is pale and abundant. The cells form small clusters or sheets. The lesion is less vascular than granulation tissue.
Though the diagnosis of histiocytosis-X needs biopsy confirmation, behaviour of the lesion and prognosis is better judged by clinical features. In 1975, Lahey introduced the concept of organ dysfunction as a prognosticator in histiocytosis-X, Komp, et al used staging for prognosis, considering combination of age and organ dysfunction at presentation. It is now uniformly agreed' that patients with involvement of bone only have good prognosis, and those with multi-system involvement i.e. reticuloendothelial system, lungs, skin, gastro-intestinal tract or soft tissues have poor prognosis.
We have therefore, categorised our cases into the two groups and have tried to correlate the histological features with clinical classification. None of the parameters were significant enough to decide whether a particular biopsy belongs to MSI or BIO. Risdall et al also have reached similar conclusions in their study of 51 cases.
In histological sections Langerhans cells may resemble monocytes and the lesion may be misdiagnosed as inflammatory. Eosinophilic granutoma in mastoid is often confused as mastoiditis. Since S-100 protein antigen is found to be positive in Langerhans cells and negative in other inflammatory histiocytes, immunoperoxidase staining of S-100 protein has been used for diagnosis of histiocytosis-X,. We have used this stain on paraffin sections of our cases and tried to grade the intensity of staining and number of positive cells. Four of six cases in MSI group showed strong positivity, yet 50% of BIO cases also revealed equally intense staining. Thus the results of such grading for judging the extent of disease are not encouraging. Since aetiology of histiocytosis-X is still not clear and histological features of localised vs. generalised disease are not demarcated, prognosis is still best predicted by clinical parameters.
Authors thank the Research Society of GS Medical College and King Edward Memorial Hospital, Mumbai, for financial assistance, and the Dean for permission to publish the material.
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