Microfilaria in lymph node mimicking Kimura disease.

In tropical and subtropical countries, parasitic infections are very rampant causing peripheral blood and or tissue eosinophilia. Here, a case of microfilaria in lymph node that produced intense eosinophil infiltrate is being reported. The dense eosinophil collection in the lymph node raised a possibility of Kimura's disease because no worms were seen in the initial sectioning of the tissue. Extensive sampling and diligent search revealed sections of microfilaria embedded in the eosinophil abscess along with foreign body giant cell reaction to its sheath material, leading to the correct diagnosis of this case.

INTRODUCTION

Filariasis is considered endemic in tropical and subtropical regions, with more than 120 million people infected, 40 million seriously incapacitated or disfigured and one billion people at risk for infection.[1] Of the infected population, 1/3 belong to India.[2]

In tropical and subtropical countries, the common cause for tissue eosinophilia is parasitic infection. In filariasis-endemic areas, it is a reaction against degenerating adult filarial worms. Microfilaria is a rare cause for lymph node eosinophilia. Several single and multiple cases of microfilaria in lymph node detected by fine needle aspiration cytology have been reported.[3-5] This case is unique in that it gives a strong message to the pathologists – to think beyond what is seen and search for the finding expected to see – before signing out a histopathology report.

CASE REPORT

A 28-year-old male presented with a single, right, level 2 cervical lymph node of 2 months duration. No other relevant history was elicited. Routine blood test showed normal total leukocyte count, with 25% eosinophils in the differential count. The lymph node excision specimen measured 2 cm in diameter, with a grey-white cut surface. Initial microscopic sections showed lymph node tissue with intense eosinophil infiltration in the paracortical, medullary and germinal center areas with focal eosinophil microabscess formation. There was prominent follicular hyperplasia. No parasites were seen in the initial sections [Figure 1].

Figure 1

Lymph node showing marked eosinophil infiltrate with eosinophil microabscess formation. Adjacent follicular hyperplasia is also seen (Hematoxylin and eosin, ×100)

Lymph node eosinophilia elicits many provisional diagnoses like Kimura disease, Hodgkin disease, hypereosinophilic syndrome/leukemia, angiolymphoid hyperplasia with eosinophilia, parasitic infection etc. Many causes of lymph node eosinophilia mentioned above were ruled out because of the absence of specific findings. Kimura disease could not be excluded. Almost all the findings like marked eosinophil infiltrate, eosinophil microabscess, follicular hyperplasia, fitted well for the diagnosis of Kimura disease, and the residents offered this as a provisional diagnosis. But, on keen observation of the initial sections, one finding did not fit into Kimura disease – the presence of focal foreign body giant cell reaction against a pale eosinophilic glassy/hyaline material [Figures 2 and 3].

Figure 2

Foreign body giant cell reaction against eosinophilic hyaline material (Hematoxylin and eosin, ×100)

Figure 3

Another focus of foreign body giant cell reaction against eosinophilic hyaline material (Hematoxylin and eosin, ×400)

Even though eosinophilic material is described in Kimura disease, it is an amorphous type of eosinophilic proteinacious material[6] without any giant cell reaction. The hyaline material led to the suspicion of a foreign body eliciting an eosinophil response and the patient being from a tropical country, the presence of a parasite was suspected.

Hence, the lymph node tissue was sectioned almost to the exhaustion of the wax block and a very careful search for an organism was made. In one or two serial sections, a few microfilariae were seen with a pale-staining ill-defined sheath and longitudinally arranged loose nuclei, the morphology suggesting microfilaria of filarial worm, possibly of Wuchereria bancrofti. The sheath is demarcated by adherence of inflammatory cells to its border, a finding also observed by Yenkeshwar et al, in their study.[3] Thus, the thought about the possibility of a hidden parasite and the action of extensive sectioning and diligent search led to the correct diagnosis of the case [Figures 4–6].

Figure 4

Microfilaria embedded in the eosinophil infiltrate (Hematoxylin and eosin, ×400)

Figure 6

Another microfilaria. The longitudinal, loosely arranged nuclear column typical of W. bancrofti species and the adherence of inflammatory cells to the border of the sheath are visible (Hematoxylin and eosin, ×1000)

High-power view of microfilaria embedded in the eosinophil infiltrate (Hematoxylin and eosin, ×1000)

DISCUSSION

Metazoan parasites – adult or larval forms – may occasionally be found in lymph nodes. Among these are Ascaris lumbricoides, Toxocara catti and Toxocara canis, Strongyloides stercoralis, Ancylostoma duodenale, Necator americanus, Trichinella spiralis, Oxyuris vermicularis, Trichuris trichura, Onchocerca volvulus and Dracunculus medinensis and the lymphatic filariasis species W. bancrofti and Brugia malayi.[6]

Filariasis is considered endemic in the tropical and subtropical regions of Asia, Africa, Central, South America and Pacific Island nations with more than 120 million people infected and one billion people at risk for infection.[1] The goal of the current campaign of the International Task Force for Disease Eradication (ITFDE) is “to eliminate lymphatic filariasis as a public health problem” by 2020.[1]

In India, lymphatic filariasis caused by W. bancrofti and B.malayi is an important public health problem. Filariasis is endemic in 17 states and six Union Territories, with about 553 million people at risk of infection.[7] It is endemic in some parts of the state of Kerala.

Adult worms reside in the lymphatics. Each fertilised adult female worm releases a large number of microfilariae into the lymphatics over a period of years. These embryonic first-stage non-infective microfilaria after being released from the uterus of female adult worm circulate in the blood stream to be sucked by their intermediate host – mosquito. Later development is in the body of the mosquito to form the stage 3 infective form of the larva, which is inoculated to the human host while the infected mosquito takes a blood meal from the humans. It is very rare to see microfilaria in the lymph node tissue which is an accidentally trapped site while the larve migrates through the blood vessels and lymphatics to be lodged in the lymphatics and mature to adult worm. Viable microfilariae in lymphatics usually do not cause lesions.[8] When the adult or larva lodge in the lymph node and die, they produce an intense inflammatory reaction with the larva in the center accompanied by dense eosinophil infiltrate with microabscess and multinucleated giant cells. Splendore–Hoeppli reaction may occur around the dead larva.[8] Eosinophils contain basic proteins toxic to some helminthes, and are a major component of the inflammatory responses to these organisms.[9]

An interesting phenomenon is ecdysis or exsheathing of the larvae in vivo and in vitro.[10] The pale eosinophilic glassy material in the lymph node seen in this case, which evoked a foreign body giant cell reaction, may be the extruded sheath material of the larva. This finding led to the suspicion of a hidden parasite.

Kimura disease is a self-limiting disease, the histology of which shows follicular hyperplasia, dense eosinophil infiltrate with microabscess formation and eosinophilic proteinaceous material in the germinal centers.[6] All the histological findings were mimicking Kimura disease. If the organism is missed by the pathologist, the case may be misdiagnosed as Kimura disease.

Correct diagnosis of the case is important because filariasis is a curable condition if efficiently treated early. But, if misdiagnosed and untreated, it will result in lymphangitis, lymphatic blockage, lymphedema and disfiguring elephantiasis in the affected organ and its inherent complications.

We are reporting this case to emphasize the fact that whenever there is tissue or peripheral blood eosinophilia, especially in a patient from tropics or subtropics, the possibility of a parasitic infection should be thought of and if the organism is not seen in the initial sections, extensive sampling, adequate serial sectioning and vigilant search should be made to arrive at a correct diagnosis and to avoid misdiagnosis and mismanagement of the patient.