Role of lymph node aspiration in diagnosing lepromatous leprosy

INTRODUCTION

Leprosy or Hansen’s disease is a disease caused by Mycobacterium leprae. It was first described by Norwegian physician Dr. Gerhard Armauer Hansen in 1874, hence the name Hansen’s disease. It is said to be an ancient disease. In India, it was first discovered in remains dated to 2000 B.C.¹ It primarily affects the skin and peripheral nerves but may also affect the nose, eyes, lymph nodes, throat and testicles.² We present a case of Lepromatous leprosy presenting with skin lesions and inguinal lymphadenopathy diagnosed on aspiration cytology of lymph nodes.

CASE REPORT

A 47-year-old male presented to the medical outpatient department with complaints of fever, generalized body weakness, dizziness, and a skin rash for the past month, accompanied by abdominal pain for 20 days. The patient was a known diabetic. The “rash” consisted of multiple erythematous to hypopigmented plaques and papules over the face, ears, and bilateral upper and lower limbs [Figure 1]. Desquamation was present over bilateral feet and lower limbs, along with nail changes. Loss of lateral eyebrows, photosensitivity, and bilateral thickening of ulnar, tibial, radial, and popliteal nerves was noted, along with tenderness in bilateral post-tibial nerves. Other general physical examination findings revealed pale conjunctivae and right inguinal lymphadenopathy. An abdominal ultrasound revealed an inflamed gall bladder.

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Figure 1:

Gross images (a to d) –A 45-year-old man presented with plaques and papules over face, bilateral upper and lower limbs and torso- a provisional diagnosis of leprosy was considered.

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Differential diagnosis consisted of Lepromatous Leprosy, Tuberculosis, airborne contact dermatitis, or Photodermatitis with Onychomycosis with Tinea pedis. Blood work was sent, and a fine needle aspiration cytology (FNAC) of inguinal lymph nodes was planned as an initial investigation. Blood tests revealed a dimorphic anemia, normal coagulation profile, elevated glycosylated hemoglobin, negative antinuclear antibody profile, and low sodium levels. Polymerase chain reaction for Tubercular bacilli was sent and came out to be negative. Based on the results of the FNAC, a slit skin smear and inguinal lymph node biopsy was sent.

The FNAC of inguinal lymph nodes revealed an admixture of neutrophils and lymphocytes. Numerous mononuclear and multinucleated histiocytes with phagocytosed material within membrane-bound vacuoles were the highlight of the aspiration cytology [Figure 2a]. Based on differentials, a Lepra stain was ordered. It showed clumps of lepra bacilli within the phagocytes [Figure 2b]. A diagnosis of Lepromatous Leprosy was given, and further investigations were advised.

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Figure 2:

Cytology images: (a) Phagocyte with vacuoles and mixed inflammatory cell infiltrate seen on lymph node aspirates (Giemsa, 400x) (black arrow), (b) Bacilli in clumps seen on Lepra stain (1000x) (black arrow), (c) Split skin smear showing clumps of bacilli (Lepra stain, 100x) (black arrow), (d) Clumps of bacilli on higher power view (Lepra stain, 1000x) (black arrow).

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Slit skin smears also revealed similar findings with lepra staining showing both intracellular and extracellular lepra bacilli clumps. A bacteriological index of 6+ was given [Figure 2c, and d].

On gross examination, lymph node showed multiple grey white nodules [Figure 3a]. Lymph node biopsy disclosed diffuse infiltration by foamy histiocytes with a few residual lymphoid follicles, and the sections were positive for acid fast bacilli [Figure 3b-e]. The skin biopsy showed a generalized inflammatory infiltrate of histiocytes, neutrophils, and lymphocytes in the dermis, obliterating the dermal architecture and separated from the epidermis via a clear Grenz zone. No well-formed granulomas were seen [Figure 3f]. Lepra stain was positive [Figure 3g].

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Figure 3:

(a) Gross images of lymph node showing multiple greyish white nodules (black arrow), (b & c) Lymph node biopsy- Sheets of foamy histiocytes and residual lymphoid follicle, respectively (H&E, 400x) (black arrow), (d & e) Lymph node biopsy- Positivity for Lepra bacilli (Lepra stain, 1000x) (black arrow), (f) Skin biopsy showing Grenz zone with diffuse infiltrate in the dermis (H&E stain, 100x) (black arrow), (g) Same section showing positivity for acid-fast bacilli (Lepra stain, 1000x) (black arrow). H&E: Hematoxylin and eosin stain.

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DISCUSSION

Leprosy bacteria are transmitted via droplets from the nose and mouth along with digital saturation of skin. The culprit, Mycobacterium leprae, is Gram-positive and weakly acid-fast. It can be observed via staining by the modified Ziehl Neelson method using a weak acid as decolorizing agent.^3,4

The clinical outcome usually depends on the immune status of the affected individual. Patients with a sturdy cell-mediated immunity show a granulomatous response and develop Tuberculoid leprosy. Whereas a poor cell-mediated immunity consists of a lackadaisical response with the absence of granulomas. This is referred to as Lepromatous leprosy. Intermediate to these two is the borderline leprosy.

The disease mainly affects the skin, peripheral nerves, mucosa of the upper respiratory tract, and the eyes, joints, and testicles. Lymph node involvement is relatively uncommon. Most Indian authors report inguinal lymphadenopathy to be the most common, followed by cervical, axillary, and epitrochlear lymph nodes.^5,6

FNAC is not considered the gold standard to diagnose Leprosy. When undertaken, it is usually performed on skin lesions. Aspiration cytology of lymph nodes is a seldom-used method to diagnose Leprosy, as lymph node involvement is considered mostly non-specific. However, over the past few years, quite a few studies have been published that tackle this particular issue.

The cytology smears in our research were observed to consist of a mixed pattern of both neutrophilic and lymphocytic infiltrate. Interspersed in between were numerous multinucleated histiocytes with several cytoplasmic vacuoles. Lepra staining showed clumps of bacilli in the cytoplasm. The slit skin smears also showed similar findings. Our findings resemble those reported by Gupta et al.⁷ (1980), Gulati et al.⁸ (2012) and Semwal et al.⁹(2018).

Aspiration from skin lesions is more commonly preferred. Numerous studies have attempted to correlate cytology and histopathology findings in Leprosy from skin lesions. In 1995, a study undertaken by Singh et al.¹⁰(1996) showed nearly 100% concordance between cytology and histology. Similar results were repo d by Rao et al.¹¹ (2001) (90% concordance, more for Lepromatous cases than Tuberculoid ones) and Nigam et al.¹² (2007) (77.3% concordance).

Lynpph node enlargement due to leprosy has been reported as early as 15^th century. However, the pattern of involvement on histopathology may be different for Lepromatous and Tuberculoid cases. For instance, in Lepromatous leprosy, only a small percentage of cases show capsular thickening and periadenitis. The most conspicuous finding in these cases is diffuse infiltration by Lepra cells. Lepra cells are large cells with vesicular nuclei and abundant pale cytoplasm with or without vacuoles. Granulomas, necrosis, sclerosis, hyaline changes, fibrosis, or calcium deposits are usually absent.

In contrast, in Tuberculoid leprosy, Lepra cells are missing from lymph node aspirates. Prominent findings include small granulomas composed of epithelioid cells with or without caseation. There is an abundance of T- T-cells in the paracortical areas, highlighting the strong immune response.

Acid-fast bacilli may be seen in both ends of spectrum, but are much more common in Lepromatous cases.^4,13-15

Our study demonstrated a diffuse infiltration and replacement of lymph node architecture via foam cells with only a few residual lymph node follicles. The subcapsular sinus and capsular integrity were unaffected. These findings are similar to Sharma and Shrivastav (1958), Chowdhury et al. (2015)^4,14,16

Thus, it can be seen that cytology is a useful tool to diagnose Leprosy. Over the years, FNAC has been used to diagnose mainly malignant and benign conditions. Its role in infectious conditions has always been limited to organisms that can be demonstrated via special staining techniques. FNAC has several advantages. It is less invasive than an excision biopsy and can be used to sample multiple nodes at the same time. The sampled nodes are also available for re-examination at a later date.¹⁰

Moreover, FNAC is faster, easier to perform, and has less turnover time.

CONCLUSION

Lymphadenopathy is an uncommon presentation of Leprosy. The role of aspiration cytology in diagnosing leprosy cannot be underestimated. It is fast, safe, non-invasive, and provides results within a short amount of time. This can help in the early diagnosis and management of patients.