Human subcutaneous dirofilariasis: A report of three cases manifesting as breast or axillary nodules.

Efstratios S. Maltezos¹, Efthimios L. Sivridis², Alexandra N. Giatromanolaki², Constantinos E. Simopoulos³

¹ Second Department of Internal Medicine, ² Department of Pathology, ³ Second Department of Surgery

Democritus University of Thrace, Regional Hospital of Alexandroupolis,

Alexandroupolis 68 100, Greece

Address for correspondence

Efstratios Maltezos, MD

PO BOX 107

68 100 Alexandroupolis, Greece

Tel. 0030-551035273, Fax 0030-551027722, E-mail: emaltez@med.duth.gr

Abstract

Human subcutaneous dirofilariasis is a rare infection caused by filarial worms of the genus Dirofilaria. The parasites are transmitted to man by zooanthropophilic bloodsucking insects and the infection is manifested as subcutaneous nodules. Excisional biopsy is both diagnostic and therapeutic. We herein report three cases of human subcutaneous dirofilariasis diagnosed, over a period of ten years (1991-2000), in North East Greece. The patients, two women and one man, were all adults between 32 and 67 years of age. In two cases the infection was manifested as breast nodules, while in the third case as a painful nodule in the axillary region. The excisional biopsy showed the presence of an adult Dirofilaria, identified as Dirofilaria (Nochtiella) repens . It is emphasised that both clinicians and pathologists should have an increased awareness of this clinicopathologic entity and include dirofilariasis in the differential diagnosis in patients presenting with breast or subcutaneous nodules.

Key words: Dirofilariasis, Dirofilaria repens, Breast, Subcutaneous, Human.

Introduction

The number of cases of human dirofilariasis reported in the last 50 years has gradually increased and the zoonosis may be described as emerging ¹. Up to date, at least 782 cases caused by D. (N.) repens were reported worldwide, and 372 of them were new cases published from 1995 to 2000². More than 270 cases have been reported in the European Union ³. Most of them have been classified as D. (N.) repens and ten only as Dirofilaria (Dirofilaria) immitis infections. The majority of these cases were detected in Italy (66%), France (21.7%), Greece (8%) and Spain (4%)^3,4,5, although a few cases have been diagnosed also in northern Europe in individuals who had previously visited countries in southern Europe³ . At least 22 cases of subcutaneous or subconjunctival human dirofilariasis and one case of pulmonary dirofilariasis have been also reported in humans in Greece ^6,7,8. In all these cases, the worms were identified as being D. repens.

We report three additionally cases of subcutaneous dirofilariasis diagnosed, over a period of ten years (1991-2000), in individuals living in the Province Evros at the North East Greece. Two of them manifested as breast nodules necessitating excisional biopsy to exclude malignancy, while the third case was presented as a painful nodule in the axillary region, mimicking an enlarged lymph node.

Case Report 1

A 55-year-old man (local farmer) presented with a slightly tendered subcutaneous nodule of the left breast. By physical examination a smooth movable nodule, of 1 cm diameter, was palpable in the upper medial aspect of the left breast. The overlying skin was normal and axillary lymph nodes were not enlarged. Routine laboratory results, including eosinophil count in blood, were normal. The lesion was excised under local anaesthesia and sent for histopathological examination to exclude malignancy. Multiple histological sections of the specimen showed abundance of granulation tissue and an intense inflammatory cell infiltrate, composed of polymorphonuclear leucocytes, lymphocytes and plasma cells, surrounding a helminth. The parasite exhibited two reproductive tubes, a single intestine, and a thick cuticle with fine external longitudinal ridges and prominent circumferential muscle cell layer interrupted by two lateral cords. (Fig. 1 and Fig. 2). According to these features, this worm was identified as an adult female Dirofilaria of the subgenus Nochtiella, most probably D. repens.

Case Report 2

A 67-year-old, female farmer, presented with a painless lump in the left breast, which had been first noted 6 months earlier. Physical examination revealed a single, firm, and movable nodule, of 1.5 cm diameter, in the upper outer quadrant of the breast. There was no nipple discharge and the overlying skin was unremarkable. Examination of the right breast was normal. Mammography showed a 1,5 cm oval density in the left breast. No microcalcifications were seen in either breast. Routine laboratory investigations, including eosinophils count, were within normal limits. Histological examination showed cross sections of a typical adult female Dirofilaria of the subgenus Nochtiella, most probably D. repens, surrounded by an intense granulomatous reaction.

Case Report 3

A 32-year-old woman was presented with a slightly tendered lump in the left axillary region. Physical examination confirmed the existence of a movable, 1 cm in diameter, nodule mimicking enlarged axillary lymph node. No breast lesion or nipple discharge was detected. Routine laboratory investigation revealed mild eosinophilia (670 eosinophils/mm³) and slight anaemia. Chest roentgenogram and a mammogram were normal. The lesion was excised under local anaesthesia and sent to the Pathology Department to exclude malignancy. Histologic examination revealed an intense inflammatory cell reaction and a nematode helminth, identified on the basis of its morphological features as D. repens.

Discussion

Human dirofilariasis is a rare parasitosis caused by a nematode helminth of the genus Dirofilaria. The most important species for man and their salient characteristics are summarized in Table 1 ^9,10,11. The dirofilarias live in the subcutaneous tissues of their hosts and produce microfilariae, which circulate in blood, and are transmitted by bloodsucking zooanthropophilic insects ¹².  Development in the mosquito requires about 2 weeks, while the sexual maturity of dirofilarias in their natural definitive hosts can be accomplished after several months¹² . After inoculation of infective larvae into human hosts during the bite of an infected insect, they can invade a variety of tissues and undergo development for an extended period without any apparent response from the host ¹³. The first reaction, usually a foreign body cell response, occurs when the parasites die in the tissues of its unnatural human host and lead to formation of nodules ¹⁴. The development of the parasites in the unnatural human host is difficult and only rarely subcutaneous nodules containing gravid female worms have been described. ^15,16

The most important risk factors regarding human infections are mosquito density, warm climate with extended mosquito breeding season, outdoors human activities and the abundance of microfilaraemic dogs^3,17. All these conditions are, apparently, fulfilled in Greece⁷. We assume, therefore, that more people may have been infected in Greece, than already reported. This hypothesis seems reasonable, given that approximately 180 cases of human dirofilariasis are reported in the neighbouring Italy, a country which is considered to have the highest number of cases in the world^{1 , 2 ,4} .

Infections in humans are usually asymptomatic and acute symptoms are noted only when living worms enter the conjunctiva. Occasionally transitory inflammatory swellings or isolated nodules are observed, which are 0.5-2.5 cm in size and may be tender or painful ¹⁸. None of our patients complained of any symptoms, apart from mild local tenderness in two cases. The subcutaneous nodules may be located anywhere in the body, but most commonly in the head, neck, extremities and thoracic wall ^2,19. Nodules in the breast and the axilla, as in our patients, or even in the lung, often raise the question of tumor growth, necessitating excisional biopsy to exclude malignancy.

The diagnosis of human subcutaneous dirofilariasis can be made with certainty only after biopsy. Blood eosinophilia or elevated serum IgE levels are rarely observed ²⁰. Therefore, eosinophil counts and measurements of total IgE levels are of limited value in screening for dirofilariasis in patients with subcutaneous lumps. Infection with D. repens induces high levels of specific IgG in humans ²¹, while elevated levels of specific IgM, IgG and IgE have been detected in patients with active D. immitis disease and also in individuals exposed to Dirofilaria species ^21,22. However, serologic tests contribute very little in detecting or identifying infections in humans, as they suffer from lack of specificity and inability to distinguish between exposure and active infection ^{17 , 22} .

The identification of dirofilarias is relied upon the microscopic features of the individual parasite, including a thick laminated cuticle with external longitudinal ridges and the presence of a well-developed circumferential musculature interrupted by two lateral cords ^17,18,23. The external longitudinal ridges are characteristic of species, which live in the subcutaneous tissues of their natural hosts ²³ . Among the dirofilarias, only D. immitis and D. lutrae have a smooth cuticle¹⁷ . The number of reproductive tubes and their contents (eggs, microfilariae or sperm) help to determine the sex of the parasite and the reproductive state of female worm ¹⁷. According to the above morphologic criteria, the Nemathelminthes identified in the excised nodules of our patients belong to the genus Dirofilaria, subgenus Nochtiella. Based on the main histological features of the parasite, the location of the nodules and the epidemiological data, these dirofilarias were further classified as D. (N.) repens. Useful characteristics for differentiating between Dirofilaria species are the size and the features of the body wall, i.e. thickness of the cuticle and its structure, ridges, lateral chords, number and type of muscle cells ¹⁷ . However, some of these morphologic features can be very variable and, in this case, identification of the parasite should closely correlated with its geographic distribution and the area where the infection was acquired ¹⁷ .  

Precise identification of Dirofilaria species may be achieved with DNA analysis, based on polymerase chain reaction ²⁴, but the large number of specific probes required limits the usefulness of this method.

Breast dirofilariasis is uncommon in the Western World. There are only 30 cases, that have been reported in USA, Canada, Italy, France, Spain and other countries^1,4,25. Breast nodules associated with dirofilariasis are occasionally misinterpreted as carcinomas, particularly when microcalcifications are visible on mammography. Calcium deposition was not a feature in our cases, and the lesions were movable on palpation, but still required excision to exclude malignancy. 

Simple extraction of the worm or complete surgical excision of the dirofilarial lesion is the treatment of choice for human dirofilariasis. Whether this condition could be treated with antifilarial medication only or the patients should receive antifilarial medication prior or after to surgical resection is not indicated in the literature. In a small number of cases ivermectin and/or diethylcarbamazine has been tried with good results ²⁶.

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