Fine needle aspiration cytology as an aid to diagnosis, categorization and treatment when pure neuritic leprosy presents as nerve abscess.

BACKGROUND: Pure neuritic leprosy (PNL) usually presents with neurological symptoms without skin involvement. Fine needle aspiration can play an important role in the management of PNL cases presenting as nerve abscesses. AIM: To assess the role of fine needle aspiration cytology (FNAC) in diagnosing and categorizing PNL cases presenting as nerve abscesses in the absence of neurological symptoms.
MATERIALS AND METHODS: Five patients with subcutaneous nerve related swellings without clinically evident neurological deficits were subjected to FNAC. As the cytological features were suggestive of nerve abscesses due to leprosy, Fite stain was performed in all cases. As none of the patients had any leprosy skin lesions, they were diagnosed as cases of PNL. Features like cellularity, caseous necrosis, presence or absence of lymphocytes, macrophages, epithelioid cells, granulomas, Langhans giant cells and nerve elements were analyzed with the bacteriological index, to categorize PNL according to the Ridley-Jopling classification.
RESULTS: Based on the cytological features and bacteriological indices, 3 cases were cytologically categorized into tuberculoid (TT)/borderline tuberculoid (BT) leprosy and the other two, as BT/borderline lepromatous (BL) and BL leprosy respectively in spite of having similar clinical presentation. Based on the cytological diagnoses, category-specific treatment could be instituted with clinical improvement.
CONCLUSIONS: The simple and minimally invasive FNAC procedure allows diagnosis and a reasonably accurate categorization of PNL presenting as nerve abscess and therefore, highly useful in its clinical management.

Introduction

Pure neuritic leprosy (PNL) consists of 4-8% of all clinical cases of leprosy.[1] It presents with symptoms and signs of neuropathy without skin lesions. Awareness of this condition and high index of suspicion are required for early diagnosis. Similar to its cutaneous counterpart, PNL is also categorized according to the Ridley-Jopling classification. Treatment of PNL varies according its spectrum. Diagnosis and categorization of PNL requires nerve biopsy, which being an invasive procedure, often results in the functional impairment of the involved nerve. There are a significant number of studies and case reports emphasizing the clinical utility of fine needle aspiration cytology (FNAC) in neuritic leprosy.[12345] We present a short series of five PNLs presenting as nerve abscess to highlight the clinical utility of FNAC.

Materials and Methods

Five cases (four males and one female) presented to the dermatology department over a period of 2 years with soft tissue swellings of insidious onset involving the upper limb. Two of the patients had tenderness while the others were asymptomatic. On examination, the swellings were soft, fusiform and subcutaneous with normal overlying skin, no fixity to the surroundings [Figure 1] and lack of local signs of inflammation. Detailed examination revealed that the swellings were part of local thickened nerve with no mobility along the long axis of the nerve and restricted mobility in perpendicular axis. All cases had single ulnar nerve involvement; however case 4 had two swellings with involvement of right ulnar and digital branch of dorsal digital nerve of right ring finger. None of the patients had any skin or neurological complaints nor clinical features of lepra reaction. Clinical details are compiled in Table 1.

Figure 1

(a) Ulnar nerve abscess and (b) nerve abscess of digital branch of dorsal digital nerve of right ring finger

Table 1

Compilation of clinical features of five cases

FNAC was done using a 10 mL syringe fitted with 23-gauge needle. Alcohol fixed smears were stained with hematoxylin and eosin (H and E); while, the air dried smears were stained with Fite and Ziehl-Neelsen (Z-N) stains. The H and E smears were evaluated for parameters like cellularity, caseous necrosis, lymphocytes, macrophages, epithelioid cells, granulomas, Langhans giant cells, nerve elements and mycobacterium leprae [Figures 2 and 3].

Figure 2

(a) Smear showing Langhans giant cell (H and E, ×100), (b) smear showing nerve elements mixed with epithelioid cells and few lymphocytes (H and E, × 400), (c) smear showing cohesive granuloma consisting of epithelioid cells and lymphocytes (H and E, ×400)

Figure 3

(a) Smear showing acid fast bacilli (Fite's stain, ×1000),(b) histopathological section showing well-formed nerve granuloma with central caseation necrosis (A) and spindle shaped nerve fibres (B) (H and E, ×100)

As the cytological findings were suggestive of leprous nerve abscess, all the patients were subjected to the ear lobe and slit skin smear preparation (from right eyebrow area) and staining for acid fast bacilli (AFB) by modified Z-N staining which were found to be negative. All the affected nerves were subjected to nerve conduction studies, which showed decreased sensory and motor conduction velocities indicating an early nerve involvement of leprosy. Lepromin test could not be performed due to non-availability of testing agents at our institute. Nerve biopsy was limited to cases 3 and 4 who underwent surgical decompression for the pain and tenderness associated with the swellings.

Results

Cytological findings

All the aspirates were purulent except the right ulnar aspirate of case 4 which was hemorrhagic. The cytological features were suggestive of leprotic nerve abscess. The aspirates were of good cellularity except for case 3. Three cases (1, 2 and 5) showed lymphocytic predominance with occasional Langhans giant cells and epithelioid cells; out of which two (2 and 5) had cohesive epithelioid granulomas as well. Macrophage-predominant pattern without epithelioid cells was noted in case 4 while case 3 showed a mixture of lymphocytes and macrophages with occasional giant cells without epithelioid cells. A positive AFB (Fite stain) with a bacteriological index (BI) of +1 and +4 was noted in cases 3 and 4 respectively. Cytological details are compiled in Table 2. Based on the cytological features, the patients were categorized in the Ridley-Jopling scale and treated accordingly. Multibacillary multidrug therapy (MDT) was instituted in cases 3 and 4 and paucibacillary MDT was started for other patients.

Table 2

Compilation of FNAC findings of five cases

Histopathological findings

Cases 3 and 4 underwent nerve biopsy. Nerve biopsy of case 3 showed numerous well defined nerve granulomas with central caseation necrosis and lymphoid infiltrates suggesting borderline tuberculoid (BT) leprosy. Case 4 showed diffuse granulomas with macrophages, lymphocytic infiltration of dermal nerves and presence of AFB suggestive of borderline lepromatous (BL) leprosy.

All patients are under regular follow-up and are symptomatically better as evidenced by regression in the size of swellings and lack of development of any new skin patches, sensory or motor complaints.

Discussion

Leprosy is a chronic granulomatous infectious disease of the skin and peripheral nerves characterized by hypoesthetic skin lesions, thickened nerves and presence of Mycobacterium Leprae in the skin smears. Among these, the cases presenting with only nerve involvement are termed as pure neuritic, poly neuritic or primary neuritic leprosy (PNL).[1] Cases of PNL are commonly seen in areas of high endemicity of leprosy with better patient immunity. Contrary to the older belief that PNL cases mostly belong to tuberculoid (TT) spectrum, recent reports suggest that it can be of any type from TT to BL in the Ridley-Jopling scale.[1236] In Indian studies, the incidence of PNL ranges from 4.3% to 10.7% and the frequency in South India is even higher; up to 18% among the newly diagnosed cases.[6] The presenting symptoms include tender, enlarged peripheral nerves along with paresthesia or numbness over the dermatome with or without motor involvement.[6]

Presentation as nerve abscess without clinically evident neurological deficit is seldom seen among PNL cases. Nerve abscess or segmental necrotizing granulomatous neuritis is formed by coalition of areas of caseous necrosis within nerve granulomas.[7] The differential diagnoses in cytological point of view include soft tissue tumors like schwannoma and neurofibroma, parasitic cyst and sporotrichosis.[1489] Cytologically, cutaneous schwannomas show slender, wavy cells with elongated nuclei.[18] The aspirate in neurofibroma is gelatinous and smears show spindle shaped nerve elements in a mucomyxoid back ground.[8] Aspirates in parasitic cyst show necrotic background with eosinophilic predominance with foreign body giant cells and occasional foreign body granulomas. Sporotrichosis should be considered whenever the swellings are seen in a linear fashion, with the cytology smears showing suppurative granuloma with plasma cells and fungal elements.[1] Apart from these, sarcoidosis also can be added to the list of clinical differential diagnoses.[1]

PNL is confirmed by nerve biopsy. But it is limited by low sensitivity, chances of sampling errors and the risk of further compromising the nerve function.[9] Other methods of diagnosis like multiple skin punch biopsies from the affected dermatome and nasal mucosa also have low sensitivity.[9] In this context FNAC seems to be a comparatively safer and simpler option with moderate sensitivity especially with already damaged nerves; however, a negative aspirate does not rule out leprosy.[7]

Though several reports are available depicting the role of FNAC in diagnosing leprosy nerve abscess with or without skin lesions,[12345] its awareness among cytopathologists is low. We have presented our cases to highlight the significance of FNAC in the appropriate management of PNL cases presenting as nerve abscesses. Inappropriate therapeutic regimen can lead to inadequate treatment, relapses and drug resistance.

Aspirate of good cellularity, cohesive epithelioid granuloma, abundant lymphocytes and BI of 0-1+ are features of TT spectrum. As reported by Prasad et al.,[3] TT spectrum can be further divided into TT and BT on the basis of epithelioid transformation, which is a feature of BT leprosy. Such differentiation becomes difficult when there are no other supportive clinical findings or histopathological evidence. Lepromatous PNL is characterized by abundant foamy macrophages, plenty of AFB and absence of cohesive epithelioid granuloma and lymphocytes. Borderline variety has intermediate features. In three patients, (Cases 1, 2 and 5) the cytological features correspond to TT spectrum. Even though case 3 cytology was in favor of borderline leprosy with deviation towards lepromatous spectrum, the nerve biopsy was suggestive of BT leprosy. This may be due to BT leprosy down grading towards midborderline or BL leprosy. In case of patient four, cytological features were suggestive of lepromatous spectrum; most probably BL as there were lymphocytes present in the aspirate. Nerve biopsy findings have confirmed this assumption.

Nerve abscess without symptoms of neurological deficit is a rare presentation of PNL. FNAC seems to be an excellent tool for early diagnosis and categorization especially in settings where clinical findings are limited. The limitations of this study are a small number of cases, lack of histopathological support in all cases and inability to perform lepromin test. Nerve biopsies were restricted to salvaging the nerves already affected with leprosy. Nonetheless, the clinical improvement seen after instituting anti leprosy treatment, indicates the accuracy of our cytological interpretation.

To conclude, a simple FNAC procedure can play a major role in the clinical management of PNL-patients presenting with nerve abscesses by facilitating their diagnosis and categorisation. Early detection of PNL is of significant importance for avoiding irreparable neurological damage.