Breast ductal carcinoma with coexistent microfilaria: Diagnosed on cytology.

Filariasis is a major health problem of the tropical and subtropical regions, but filariae are also found in temperate climates. The disease is endemic all over India and microfilariae have been observed as coincidental findings with inflammatory conditions and neoplastic lesions. We report a rare case of a 40-year-old female from a nonendemic area presenting with lump in the left breast. The skin overlying the mass was fungating and ulcerated. Ipsilateral axillary lymph nodes were palpable. Fine-needle aspiration cytology revealed highly cellular smears having ductal epithelial cells arranged in groups, tight clusters, and scattered singly. Cells were large, having pleomorphic round to oval nuclei with prominent nucleoli. Along with these tumor cells, sheathed microfilariae of Wuchureria bancrofti were seen, suggesting a diagnosis of ductal carcinoma with coexistent microfilaria of W. bancrofti. Findings were confirmed on histopathology of the resected specimen following modified radical mastectomy. Coexistent pathologies should always be considered while reporting.

INTRODUCTION

Filariasis is a major health problem in tropical countries, especially India.[1] Wuchereria bancrofti is the most common causative organism accounting for majority of cases (90%–95%). Despite the high prevalence rate, it is rare to find microfilariae in cytology smears and body fluids.[2] Microfilariae have been observed as coincidental findings with various benign and malignant tumors. We present a rare case in which microfilariae were encountered in the fine-needle aspiration of a patient with Infiltrating ductal carcinoma.[13]

CASE REPORT

A 40-year-old female patient presented with a nontender lump in the left breast measuring 8 cm × 6.5 cm × 6.0 cm, since the past few months. The swelling was large, nodular, with ill-defined borders, soft to firm in consistency. Skin overlying the swelling was fungating and ulcerated. The nipple was retracted and puckered. Ipsilateral lymph nodes were palpable. Mammography showed ill-defined hypodense area within the left breast with focal hyperechoic regions. Fine-needle aspiration cytology (FNAC) was done from the breast swelling as well as from the lymph nodes. Smears stained with Giemsa and papanicolaou stain were highly cellular and revealed ductal epithelial cells arranged in groups, tight clusters, and scattered singly. Cells were large, having pleomorphic round to oval nuclei with prominent nucleoli [Figure 1a]. No myoepithelial cells were seen in the aspirate. Cellular dissociation was Grade II with good number of cells seen scattered singly. The background showed polymorphonuclear inflammatory infiltrate along with hemorrhage. Along with these tumor cells, sheathed microfilariae of W. bancrofti having multiple, coarse, discrete nuclei extending from the head to the tail, except in the small terminal portion of the caudal end were present [Figure 1b]. Based on these features, a diagnosis of ductal carcinoma of the breast (Robinson's Grade II having a score of 12) with coexistent microfilarial infestation was given.

Figure 1

(a) Cytosmears showing malignant ductal epithelial cell clusters. (b) Sheathed structure of Wuchereria bancrofti with nuclei (←) and tail without nuclei (→). (c) Microfilarial sheath and nuclei amongst dispersed tumour cells. (d) Microfilarial sheath (↓) with multinucleate giant cell reaction (→) and neoplastic ductal cells (←)

Based on radiological and cytological findings, total radical mastectomy was done through pectoralis muscle dissection. Two lymph nodes were identified and dissected out. Histopathology of the excised tissue showed, infiltrating duct carcinoma of the left breast (T4bN0M0 stage) [Figure 1c], with focal areas of giant cell reaction [Figure 1d]. On serial sectioning sheaths of W. bancrofti were evident, along with eosinophilic infiltrate and granulomatous reaction, which proved the cytology findings [Figure 1c and d]. Sections from lymph node tissues showed reactive hyperplasia only. The patient was referred for radiotherapy and chemotherapy but was lost to follow-up. Estrogen receptor (ER), progesterone receptor (PR), and Her2neu were applied on the sections, which showed ER positivity, PR positivity, and Her2neu negativity. The findings of cytology and histopathology were concomitant.

DISCUSSION

Filariasis is prevalent in most parts of the world and is endemic in Southeast Asia.[4] An estimated 120 million people are infected worldwide, more commonly in the tropical regions. Filariasis is rare in temperate zones. In India, lymphatic filariasis is common in most parts of the north, including Uttar Pradesh where an estimated more than 60 million people are infected, forming a major cause of morbidity in this region.[35]

W. bancrofti is responsible for 90% of filariasis. The larvae are transmitted by bite of Culex mosquito, during its feed. The larvae enter through the skin into the lymphatics and migrate to the lymph nodes where they stay for few months and mature into adult forms. Adults can remain in the lymph nodes for many years. The female worm fertilizes and discharges thousands of microfilariae that enter the peripheral blood or stay in the lymphatics for several years.[3]

Several authors have reported the presence of microfilaremia at various sites including lymph nodes, bone marrow, bronchial washings, pleural and pericardial fluids, ovarian cyst fluid, and cervicovaginal smears. Only few cases have been reported in FNAC of various tissues, despite the high incidence rates. Breast, including the axillary lymph nodes, is an uncommon site for filariasis.[6] The association of microfilariae with primary malignant breast lesions is not known, and are rarely reported.[78] Many a times in a background of carcinoma, the concomitant filarial worm may be missed or overlooked. The presence of eosinophilia and foreign body giant cell reaction, though minimal, should always raise a suspicion for coexistent parasitic infestation, especially in endemic areas like India. Calcified filariae may be appreciated on mammography.[9]

Criteria for diagnosis of infiltrating ductal carcinoma (NOS) of breast are moderate to cellular smears. There is a variable loss of cell cohesion alongside single population of epithelial cells, with the absence of myoepithelial cells and single bare bipolar nuclei. There are single epithelial cells with intact cytoplasm. The cells show moderate-to-severe nuclear enlargement with atypia, exhibit pleomorphism along with irregular nuclear membrane and chromatin.

Microfilaria of W. bancrofti, Brugia malayi, Brugia timori has sheaths. W. bancrofti measures about 260 μm × 8 μm, whereas those of B. malayi are slightly shorter and can be distinguished from microfilaria of W. bancrofti by the presence of two isolated nuclei at the tip of the tail and the absence of nuclei in the cephalic space. Microfilariae of B. timori are longer than these of B. malayi.

Examination of peripheral blood smear from blood drawn at night, with and without diethylcarbamazine provocation therapy, did not show the presence of any microfilariae, or eosiniphilia in our case, which strengthens the fact that filariasis, can exist without microfilaremia and therefore frequently overlooked. A possible explanation for tissue filariasis is that microfilariae usually circulate in peripheral blood, and only reach tissue fluids and dead end sites when there is obstruction, which may be due to scars, tumors or vascular stasis. Vascular and lymphatic obstruction and damage lead to extravasation of blood and lymph, which releases microfilariae into adjacent tissue. Tumours have a rich blood supply, and this may be a cause for migration of microfilariae to these sites. During aspiration or vessel damage, leading to hemorrhage, release of microfilariae occurs. This happens most frequently in cases of superficially palpable lesions, including malignancies.[610]

CONCLUSION

The presence of microfilaria in fine-needle aspirates is a common finding. However, the presence of microfilariae with coexistent neoplastic lesion of the breast is rare and indicates that the patient might be harboring subclinical filariasis during the development of tumor. Such cases are usually seen when a careful search is made on cytology smears, driven by evidence of eosinophilia or foreign body giant cell reaction. Thus, a careful screening of all the cytology smears should always be made, even in a background of malignant lesion and also in the absence of peripheral eosinophilia.

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Conflicts of interest

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