The histopathological approach to granulomatous skin lesions

Introduction: Granulomatous inflammation of skin and subcutaneous tissue are common in India. An identical histological picture is produced by several causes. Present study aims at classifying infectious granulomas based on histomorphology and special staining and developing a proper approach for making a specific etiological diagnosis. Aims: To classify the granulomatous dermatitis and a simple diagnostic histological approach has been worked out based on morphology of granuloma, presence of caseous necrosis, palisading necrosis, location of the granuloma and use of special stains. Materials and Methods: A prospective study of skin biopsies with granulomatous inflammation over a period of 2 years is done. Histologically lesions were divided into six subtypes:-Tuberculoid, foreign body type, histoid, necrobiotic, suppurative and sarcoidal type. On basis of morphological features and special staining each type was further subclassified and a specific diagnosis was given. Results: Among 580 skin biopsies, 175 cases (30.17%) were of granulomatous skin lesions. On histopathological typing Tuberculoid type of granuloma was the most common type (62/175 cases, 35.43%) of which leprosy (40/62 cases, 64.52%) was the commonest etiology identified. Infections form an important etiology of granulomatous skin inflammation (120/175 cases, 68.57%) of which leprosy (82/120 cases, 68.33%) is the leading etiology in our study. Conclusion: Adequate clinical work-up in combination with pathological resources help in correctly approaching a granulomatous skin lesion and reaching a specific etiologic diagnosis. © 2020 Published by Innovative Publication. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by/4.0/)


Introduction
Granulomatous inflammation is a distinctive pattern of chronic inflammation due to tissue reaction against various organic and inorganic antigens, which are often resistant to be eliminated. 1 Granulomatous dermatitis frequently poses a diagnostic challenge to dermatopathologists, since an identical histologic picture is produced by several causes and conversely a single cause may produce varied histologic patterns. 2 However, good clinical history, histopathological examination and clinicopathological correlation is mandatory in arriving at a proper diagnosis so that appropriate treatment can be meted out. 3 Our study aimed at classifying the granulomatous dermatitis and a simple diagnostic histological approach has been worked out based on morphology of granuloma, presence of caseous necrosis, palisading necrosis, location of the granuloma and use of special stains.

Materials and Methods
The histopathological study of granulomatous dermatitis was carried out in histopathology department of Pathology, over a period of 2 years from May 2017 to April 2019. Most of the patient's specimen for histopathological study in our institute were received from OPD and indoor patients from Skin, ENT, Orthopaedics and Surgery departments after incisional and excisional skin biopsies and other surgical https://doi.org/10.18231/j.jdpo.2020.012 2581-3714/© 2020 Innovative Publication, All rights reserved. 57 procedures after taking written informed consent. This study was conducted with the permission of the institutional ethics committee and required procedures were performed according to the declaration of Helsinki. A study of total 580 cases of skin lesions was done. For histopathological examination, specimens were received in 10% formalin. In histopathology department specimens were processed and sections were stained by Haematoxylin and Eosin (H&E) stain. Special stains like Ziehl Neelson (ZN), Periodic acid Schiff (PAS), Fite Faraco, and Giemsa stain were used wherever required. The relevant clinical details and laboratory investigations were collected from the hospital records.
One case of Sarcoidosis was diagnosed by morphology and special staining and was classified into sarcoidal type of granulomatous lesion.
A total of 175 cases of granulomatous dermatitis were identified, of which 120 cases (68.57%) were categorized in infectious granulomatous dermatitis and 55 cases (31.43%) into non-infectious dermatitis. The age of patients ranged from 10years to 75 years. Male (99/175) to female (76/175) ratio is 1.3: 1

Discussion
Granulomatous inflammation of skin comprises a spectrum of diseases sharing the common denominator of granuloma formation. 4 A granuloma is a collection of mononuclear cells usually as a result of type IV hypersensitivity reaction in response to an antigen or persistence of non-degradable product. 1 Granulomatous diseases have been previously classified on the basis of pathophysiology, etiology, immunology and      morphology. In the present study granulomatous dermatitis was classified using combination of histopathological findings and special staining. Six histological types of granulomas were identified on the basis of the constituent cells and other changes within the granuloma: 1) Tuberculoid, 2) Foreign body type, 3) Suppurative, 4) Histoid, 5) Necrobiotic, 6) Sarcoidal.
Among tuberculoid type granuloma an attempt has been made to identify characteristic pattern of involvement among Tuberculosis verruca cutis, Lupus vulgaris, Scrofuloderma, Tuberculoid leprosy, Borderline tuberculoid leprosy and few fungal granulomas. Granuloma in Tuberculoid leprosy and Borderline tuberculoid leprosy are seen along the neurovascular bundles and superficial vascular plexus whereas granuloma of Tuberculosis verruca cutis, Lupus vulgaris, Scrofuloderma and fungal granulomas, usually involve full thickness of the dermis. Granulomas of Borderline tuberculoid leprosy donot infiltrate into the epidermis where as granulomas of Tuberculoid leprosy are seen infiltrating the epidermis. 5 We further subdivided tuberculoid granulomas based on cell component predominantly epithelioid cells. In Tuberculosis verruca cutis and Lupus vulgaris epithelioid cells are present in fair number where as in fungal granulomas number of epithelioid cells are scant to absent. 5 Predominantly epithelioid cell granulomas with moderate necrosis were diagnosed as Tuberculosis verruca cutis and those with slight or absent necrosis were diagnosed as Lupus vulgaris. Scant or absent epithelioid cell granulomas were Bacilli were absent in case of Tuberculoid leprosy. 5 The sex distribution pattern revealed that most of the patients were males (56.57%) which is in concordance with study of AmanjitBal et al 2 and Ashkakodnani et al 6 .The age distribution pattern revealed that maximum cases were in the age range of 31-40 years in contrast to the study of In the present study, largest group of lesions were of tuberculoid granuloma (62/175 cases, 35.43%). Similar findings were seen in the study of Srabanichakrabarti et al 1 .Second most common group of lesions in our study were of foreign body type granuloma (51/175 cases, 29.14%) which is in contrast to study of Srabanichakrabati et al 1 where second most common lesions were of necrobiotic type granulomas.
In our study, 68.57% cases (120/175) were due to infectious etiology and leprosy was the commonest specific cause (68.33%, 82/120 cases) which is similar to the findings of Jayawardhana et al (39.8%) 8 and AmanjitBal et al (72.4%) 2 second commonest infectious etiology was tuberculosis (21/120 cases, 17.50%). In series of R Singh et al 7 , Amanjitbal et al 2 and Jayawardhana et al 8 similar findings were seen with incidence of tuberculosis being 42.31%, 23.1%, and 13.3% of cases respectively.

Conclusion
Histopathological approach along with special staining is gold standard for diagnosis and categorization of granulomatous skin lesions. The classical clinical features may be absent and identifying the agent may not be always possible hence adequate work up in combination with histopathology and special staining help in making correct specific diagnosis.

Source of funding
None.

Conflict of interest
None.