The present study was carried at the department of Pathology at tertiary care hospital over 18 months from February 2018 to July 2019.

• Selection of cases:
  • Inclusion criteria:
    • Cases diagnosed as granulomatous inflammation on FNAC
  • Exclusion criteria:
    • Acellular smears/smears with crushed morphology or poorly stained slides will be excluded.
    • Previously diagnosed cases and cases already taking AKT.

Patients fulfilling inclusion criteria will be selected from fine needle aspiration cytology specimens after written consent. A routine stain like Hematoxylin and eosin (H&E), Papanicolaou (PAP) and Giemsa stain will be done. Two extra unstained slides will be smeared from aspiration material. One slide will be stained by Ziehl Nelson's (ZN) stain. The second slide will be stained with Periodic Acid Schiff stain (PAS).

Total 156 patients with granulomatous inflammation diagnosed on FNAC were taken. Granulomas were described as comprising of pale staining epithelioid cells which were round to oval to spindle against an eosinophilic background.

Table-1: Sex distribution of cases

As shown in Table-1, a slight female preponderance was observed. The male to female ratio was 1.0 to 1.4.

In this study the age of cases ranged from 3 months to 77 years.

As per Table-2, the maximum incidence was in the age group of 21 to 30 years (41 cases).

Table-2: Age wise distribution of cases

As shown in Table-4, the ZN stain for acid-fast bacilli was positive in 111 cases and negative in 45 cases. Granulomatous inflammation with positive ZN stain was diagnosed as tuberculosis. PAS stain for fungus was positive in 5 cases.

Out of a total of 156 cases, caseation present in 102 cases and absent in 54 cases. Total 102 cases with caseation, 99 cases were of tuberculosis and 1 case of fungal infection. In the remaining 2 cases of granulomatous inflammation, the cause of caseation was not detected. There was an association between AFB positivity and caseation necrosis. We have found 99 cases (89.18%) with caseation out of a total of 111 AFB positive cases, while only 3 cases were found without caseation. Multinucleated giant cells were present in the smear of 51 (32.69%); cases. (Table- 5)

Table-5: Correlation of caseation with ZN stain

The granulomatous lesion is seen in a large number of diseases. It is seen in various types of infections, foreign body reactions, aberrant immune reactions and secondary responses in lymph nodes draining carcinoma. [8]. It is also seen in some cases of lymphomas. [9]. Granulomas are most commonly found in routine practice which is characterized by the formation of distinct granulomas composed of aggregates of epithelioid histiocytes, with a peripheral cuff of lymphocytes and plasma cells, and occasionally a necrotic centre. To treat these lesions, demonstration of the etiological agent for definitive diagnosis is essential, which will help inpatient management and outcome. [10].

In developing countries like India, tuberculosis is the most common cause of granulomatous inflammation. Early diagnosis and effective treatment are important for TB control. The diagnosis of TB is confirmed by isolating M. tuberculosis or by finding specific DNA sequences in aspirates. Fine needle aspiration cytology is an inexpensive, less invasive procedure for early diagnosis of such tuberculosis and timely initiation of a specific therapy. [11]. FNAC plays an important role in the diagnosis of tuberculous inflammation and prevents unnecessary surgery.

Figure-1: Well-formed epithelioid cell granuloma in the background of caseation in tuberculosis (H& E stain-40x)

The most common cause of granuloma in this study was tuberculosis (111 cases) (Figure-1&2), which is in concordance with findings of another study of Permi HS et al and Pawale JS et al. [13,14]. However, the second most common infectious cause was fungal infection (Figure-3) in this study.

Figure-2: Acid fast bacilli in background of caseous necrosis (ZN stain-100x)

Figure-3: Fungal septate hyphae (PAS stain-40x)

A similar finding was observed in the study of

The clinical features of peripheral lymphadenopathy caused by tuberculosis and malignancies are similar. In both conditions, patients have features like painless swelling, weight loss and decreased appetite. Sometimes, cytological findings of granulomas in carcinoma and lymphoma obscure primary malignancy and may favour the underdiagnosis of such cases as infectious etiologies. For appropriate and timely management of these cases, proper identification of the cause of granulomatous inflammation is mandatory. Many mechanisms have been described for the formation of granulomas in malignancies. Antigens, most likely derived from tumour cells, could elicit a hypersensitivity reaction mediated by T-helper cells and thereby stimulate the activation of monocytes to form epithelioid histiocytes. [25].

The insignificant number of cases (21.15%), the cause of granuloma was not known in this study, this finding is similar to the study of Adhikari RC et al. [18]. In the present study of 156 cases of granulomatous inflammation, 111 cases showed positivity for acid-fast bacilli. This finding is agreed with Krishnaswamy H et al. [21]. Whereas it is 44% in the study of Mudassar et al, 45.8% in the study of Das et al and 59.4% in the study of Bezabih et al. [19,27,28]. AFB positivity was notably and more commonly found in granulomatous inflammation with caseous necrosis. 99 out of 111 AFB positive cases associated with caseation necrosis (89.18%), in the current study. This finding is consistently seen in the study of Bezabih et al and Mudassar et al. [28,19].

This study concludes that even after highly effective anti-tubercular treatment, tuberculosis remains the leading cause of granulomatous lesions. FNAC is still a good diagnostic tool in the evaluation of granulomatous lesions. Patients who are not responding to empirical AKT should be considered for other causes of granulomatous inflammation other than TB, and proper workup should be done. This study confirmed the diagnosis of Hodgkin’s lymphoma and few cases of malignancies with the granulomatous reaction that almost masked the malignant component. This reveals out the value of a detailed cytological study in all granulomatous reactions, because of highlighting the malignancy if present. There is a subtle but definite association between malignancy and benign granulomatous inflammation.