Dirofilariasis is caused by zoonotic filarial nematodes that primarily parasitize carnivores and are transmitted by various mosquito species depending on geographic distribution and Dirofilaria species (1). In human infections, the most commonly described species are D. immitis, which predominantly causes pulmonary dirofilariasis, and D. repens, D. tenuis, and D. ursi, which typically cause subcutaneous infections (1). The recently described D. asiatica, previously reported as Candidatus Dirofilaria hongkongensis, accounts for a further group of subcutaneous infections in Asia (2).
D. repens is the most frequently identified nematode species in human subcutaneous dirofilariasis, particularly in the Old World (1). Its primary vectors are mosquitoes of the Culicidae family, and the definitive hosts are typically canids and felids (3). The infection has been most commonly reported from Italy, India, Japan, and France (3). In most of those reports, the species was assigned on morphologic grounds, without molecular confirmation (3). The typical clinical manifestation of D. repens infection in humans is an isolated subcutaneous nodule, but rare cases also have worm maturation and microfilaremia (4–6). The upper body (head and neck) is the most common site of human D. repens infection; ocular and periocular sites alone account for ≈22% of all reported human dirofilariasis cases (subconjunctiva ≈16%, eyelid ≈7%) (3), but breast involvement is comparatively rare. We report a previously unpublished case of breast dirofilariasis from Israel. We also conducted a systematic review of the literature to assess breast dirofilariasis epidemiologic patterns, clinical manifestations, and diagnostic considerations.
Case Report
In February 2010, an asymptomatic woman in her 50s with a history of benign breast cysts underwent routine annual mammography and breast ultrasound. Comparison with imaging performed 1 year earlier revealed no new abnormalities on mammography; however, ultrasonography identified a new 1.4-cm mixed-echogenic structure in the left breast. Two radiologists independently reviewed the images: 1 assigned a Breast Imaging-Reporting and Data System (BI-RADS) category of 3 (probably benign) and the other a category of 4 (suspicious). In view of that discordance and the patient’s preference for definitive characterization, the lesion was managed as BI-RADS 4, which prompted tissue sampling.
Figure 1
Figure 1. Pathological findings from a case of human breast dirofilariasis, Israel, 2010. Hematoxylin and eosin–stained histopathology of the excised breast nodule from the patient reported in this study. A) Transverse sections…
Laboratory study results were within reference limits, including complete blood count, differential leukocyte count, and inflammatory markers; the absolute eosinophil count was within the reference range (no peripheral eosinophilia). Physical examination revealed no palpable abnormality. A core-needle (Tru-Cut; Merit Medical, https://www.merit.com) biopsy was performed, and histopathology examination demonstrated a parasitic worm. Histological images of the specimen were forwarded to the Centers for Disease Control and Prevention (Atlanta, GA, USA), where the parasite was identified as a Dirofilaria species nematode morphologically consistent with D. repens on the basis of a thick, multilayered cuticle, prominent musculature, and paired reproductive tubes (Figure 1). Molecular confirmation, filarial serology, and circulating filarial antigen testing were not performed.
The patient resided in an urban setting in central Israel. In the 2 years preceding diagnosis, she had traveled to Southeast Asia, Central Europe, and North America. She kept a domestic cat, whose infection status was unknown; cats are generally considered poor or dead-end hosts for D. repens nematodes and have low microfilaremia (1), making pet-related transmission an unlikely route. The cat was not tested; available assays are neither sensitive nor species-specific in cats (1), and transmission requires a mosquito vector.
Of the patient’s travel destinations, Central Europe includes recognized D. repens–endemic areas (3) and cannot be excluded as the source of infection. However, autochthonous transmission is also plausible: D. repens infection has been documented in dogs in Israel, and human cases have been reported from the country and the wider Eastern Mediterranean basin (7). Therefore, the geographic source of infection in this patient could not be determined with certainty. Because species assignment rested on morphology alone, D. tenuis nematode, the principal agent of subcutaneous dirofilariasis in North America and morphologically close to D. repens (1,8), cannot be formally excluded, considering her travel to North America.
The excisional biopsy was both diagnostic and therapeutic. No additional treatment was administered, and the patient had an uneventful recovery with no recurrence on follow-up imaging. Another case of dirofilariasis in 2025 prompted us to look back for breast involvement; we identified this 2010 case in that reexamination, and it led us to conduct a systematic review of the literature on breast dirofilariasis.
Systematic Review Methods
Information Sources and Search Strategy
We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement (9). We searched PubMed/MEDLINE (National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov), Embase (https://www.embase.com), and Scopus (https://www.scopus.com) databases from inception to May 11, 2026. For PubMed, we used the search string (“Dirofilaria”[MeSH] OR “Dirofilariasis”[MeSH] OR dirofilaria*[tiab] OR dirofilarias*[tiab]) AND (“Breast”[MeSH] OR “Mammary Glands, Human”[MeSH] OR breast*[tiab] OR mammary[tiab]). We used equivalent strings adapted to Embase (Emtree) and Scopus syntax for the other databases. We hand searched reference lists of all included articles and of relevant review articles. We did not apply any date or language restrictions; we translated non-English papers by using published abstracts and, where necessary, we used the Claude (Anthropic, https://claude.com) large language model to assist with translation. We did not search gray literature, conference abstracts, or unpublished data.
Eligibility Criteria
We included peer-reviewed case reports and case series in any language describing histopathologically or molecularly confirmed Dirofilaria infection in which the breast was the primary anatomic site of the lesion. We excluded animal-only studies, narrative reviews without primary patient data, and reports in which the breast was involved only as a secondary or metastatic lesion or in which the nematode species was not Dirofilaria. We excluded cases of axillary or chest-wall involvement without breast tissue invasion; we also excluded intramuscular, orbital, or other nonbreast localization described in patients with a history of breast disease.
Selection Process
We exported records to a shared library and deduplicated the collection. Two reviewers (D.G. and E.S.) independently screened titles and abstracts and then full texts against the eligibility criteria. Disagreements were resolved by discussion.
Data Items
From each included report we extracted year of case occurrence (when stated) and year of publication; and reporting country and country of probable origin (travel history). We also extracted patient sex and age; clinical symptoms and laterality; imaging findings and BI-RADS category, where reported; method of diagnosis (cytology, histology, molecular); causative Dirofilaria species; treatment; and outcome.
Risk of Bias and Quality Appraisal
All included publications were single-patient case reports or small case series spanning >6 decades; thus, we did not perform a formal report-by-report critical appraisal, for example, by using the JBI checklist for case reports (https://jbi.global/sites/default/files/2020-08/Checklist_for_Case_Reports.pdf). The inherent limitations of case-report literature, such as variable depth of reporting, inconsistent or absent follow-up, and the inability to formally assess publication bias, apply to the corpus, and we address those in the limitations section of the discussion. We did not exclude any reports on the basis of quality.
Synthesis
Given the heterogeneity of case-level reports, we did not perform quantitative synthesis (meta-analysis). We descriptively summarized results with frequencies and percentages for categorical variables, and median and range for continuous variables; we reported denominators throughout because individual data items were missing in a variable number of cases.
Study Selection
We interrogated the 3 databases on May 11, 2026, by using the Boolean strings described. Our search returned 49 records from PubMed/MEDLINE, 60 from Embase, and 71 from Scopus, for a total of 180 records identified through database search. Through hand-searching reference lists of included papers and The Breast Journal, we added 10 reports. Of those 10 reports, 9 were historical reports cited in primary papers but not retrievable via the 3 databases, including a 1980 report published in a nonindexed journal from Japan (10); the 10th was a 2015 report published in a nonindexed journal from Iran (11). After deduplication (68 duplicates removed), we screened 101 unique records by title and abstract and excluded 63 records deemed not relevant. Of 38 reports sought for retrieval, 1 could not be obtained through institutional channels and was excluded from full-text assessment. We assessed the remaining 37 reports in full and excluded 3 additional reports: 2 were conference abstracts and the other was a veterinary report describing dirofilariasis in a dog. Thus, we included 34 source reports describing 39 human cases that met all inclusion criteria (10–44). Combined with the previously unpublished case from Israel we described, we included 40 patients in the qualitative synthesis (Figure 2).
Epidemiologic Analysis
Figure 3
Figure 3. Geographic distribution of 40 reported breast dirofilariasis cases, 1959–2025. A) Number of breast dirofilariasis cases by reporting country; B) number of cases by country of Dirofilaria spp. infection.
The 40 patients with breast dirofilariasis were reported during 1959–2025 (Table; Figure 3). Most (95%, 38/40) patients were female; only 2 (5%) were male. Age was reported for all 40 patients, and median age was 50 (range 25–70) years.
By reporting country, the continent of Europe accounted for 19 (48%) cases, Asia accounted for 11 (28%), and North America contributed 5 (13%). Other reporting countries included Tunisia with 3 (8%) cases and Israel and Australia with 1 (2.5%) each. No cases were identified from sub-Saharan Africa (Figure 3, panel A).
Figure 4
Figure 4. Number of reported cases of breast dirofilariasis by decade of publication, 1959–2025. Of 40 reported cases, 31 occurred during 1990–May 2026. Dotted vertical line separates 1959–1989 (n = 9) from…
When we geographically reclassified the cases by country of acquisition (Figure 3, panel B), the clustering tightened. Cases acquired in the Mediterranean rim (Italy, France, Tunisia, Israel, Croatia, and Greece) accounted for 21 (53%) patients; India contributed a further 6 (15%) cases, predominantly from coastal Karnataka and northern Kerala. Together, those 2 regions accounted for 68% (n = 27) of reported cases, broadly mirroring the geographic distribution of canine D. repens reservoirs and competent Aedes spp. and Culex spp. mosquito vectors (7). Temporal analysis revealed that reported cases began increasing in the 1980s (Figure 4).
Clinical Manifestation, Diagnosis, and Outcomes
The typical clinical manifestation among patients was a solitary, well-circumscribed nodule measuring 1–2 cm in diameter. Among the 40 patients, 34 (85%) had a palpable mass, and 6 (15%) nodules were detected incidentally on routine breast imaging. When symptomatic, patients reported mild localized pain (n = 5), pruritus (n = 2), or erythema (n = 3), but most were asymptomatic.
Imaging findings were reported heterogeneously across the reports included. Among the 10 patients in whom both mammography and ultrasound were documented, ultrasound identified the lesion in 10 (100%) and mammography identified the lesion in 5 (50%). Lesions were mammographically occult in 4 patients, our case from Israel and 3 others (30,33,34,37), and mammography was nondiagnostic in 1 case (25). On mammography, when lesions were visible, they appeared as well-circumscribed nodules without microcalcifications. On ultrasound, lesions typically appeared as well-defined hypoechoic or mixed-echogenic nodules, often containing internal echogenic rod-like or coiled structures suggestive of a parasitic etiology (28,36). No comprehensive description of magnetic resonance imaging findings was available in the literature.
In all cases, histopathologic examination of the excised specimen, or of fine-needle aspirate in 2 cases, established a definitive diagnosis of dirofilariasis. However, for most (92.5%, 37/40) cases, species-level attribution rested on morphology alone. D. repens was the most commonly reported (77.5%, 31/40) species, including for 2 early reports using the synonym D. conjunctivae and 1 whose species, on the basis of cuticular ridge number and spacing, appears in the answer of the 2-part publication (33,34). Two cases were attributed to D. immitis on histopathology alone (10,17), and in 1 of those the worm had a smooth cuticle without external longitudinal ridges (10). Two other cases were attributed to D. tenuis nematodes (15,16), both of which were acquired in North America. Three cases were reported as Dirofilaria nematode without species assignment (41,43,44), 1 of which had D. immitis proposed on the basis of an unspecified serologic assay (43), but we do not regard that diagnosis as species confirmatory. One case was identified as D. asiatica nematode, reported at the time as Candidatus D. hongkongensis, by molecular analysis (42). One report did not specify a species (28). Molecular confirmation was performed in only 2 (5%) of 40 cases (39,42), and multilocus enzyme electrophoresis in 1 further case (20). Because morphologic features overlap between D. repens, D. tenuis, D. immitis, and D. asiatica nematodes, and because histologic sections are less informative than an intact worm or microfilariae, species assignments made on morphology alone are better read as probable than as definitive (8,45); serology is likewise not reliably species-specific (1).
Peripheral blood eosinophil status was documented in only 10 of 34 source reports; in every report where the value was given, the eosinophil count was within normal limits or peripheral eosinophilia was explicitly absent. Eosinophilic infiltrate was a near-universal finding on histopathology but did not correlate with systemic eosinophilia. Preoperative diagnosis via fine-needle aspiration cytology (FNAC) was attempted in 9 cases, including 2 where FNAC was nondiagnostic for parasites (32,38); only 4 instances had parasitic elements identified by FNAC.
All infections were successfully resolved with excisional biopsy or surgical removal. No complications or recurrences were reported in any published cases with available follow-up information.
Our review demonstrates a notable increase in reported cases of human breast dirofilariasis since the 1980s (Figure 4), paralleling the global rise in reported human dirofilariasis overall (3). Human dirofilariasis has been described across diverse geographic regions, and the highest numbers have been reported from Italy, India, and Greece, but breast involvement appears to cluster predominantly in Europe, particularly within the Mediterranean basin. That distribution likely reflects both true endemicity and detection-related factors, including the availability of breast imaging and publication bias.
From a One Health perspective, the geographic distribution pattern mirrors the increasing reported canine prevalence of D. repens nematodes in southern Europe, documented largely by PCR-confirmed surveys rather than by species-specific serology and the geographic expansion of competent mosquito vectors (7). Aedes albopictus mosquitoes, originally introduced into Europe from Asia, have been confirmed both experimentally and in field studies as a competent vector for D. repens nematodes, alongside the traditional Culex pipiens mosquitoes (7). Those observations support integrated vector control and canine prophylaxis as the most effective preventive measures (7). Climate-driven northward expansion of competent mosquito vectors has been well documented for other vectorborne diseases, such as dengue and chikungunya (46), and a similar mechanism is plausible for Dirofilaria spp. nematodes, although direct evidence remains limited.
A notable finding in our review was the absence of pediatric cases of breast dirofilariasis. Despite children frequently sharing the same outdoor environments and mosquito exposure as adults in endemic regions, this observation suggests possible age-related differences in cumulative exposure time or in immune response to incoming larvae. Similar findings have been reported previously, with only 4% of human dirofilariasis cases occurring in children 3). That age distribution contrasts with many other vectorborne diseases that affect children and adults more equally and warrants further investigation into host, vector, and parasite factors, including breast-specific anatomy as a determinant of tissue affinity and hormonal or immunological influences.
The breast is an unusual site for a mosquitoborne parasite because that site is generally covered and less accessible to mosquito bites. The most plausible explanation is postinoculation larval migration: larvae inoculated at exposed sites such as the face, arms, or neck might migrate subcutaneously and lodge in breast tissue, which is richly supplied with blood and lymphatic fluid, and similar migration may account for other atypical sites such as the penis and scrotum (7). Mosquitoes also can feed through light clothing or at night while patients are partly uncovered, the principal Culex vectors being night-biting (47,48). Those mechanisms would explain access to the breast rather than any specific affinity for breast tissue, for which no direct evidence is available.
The marked female predominance observed in our cohort is particularly striking. Whereas human dirofilariasis overall demonstrates only a slight female predominance (≈54%), and D. repens infections are reported with an essentially balanced sex distribution (3), 38 (95%) of 40 breast cases with reported sex occurred in women. Several nonexclusive explanations might account for that finding. First, ascertainment bias is likely substantial, because women routinely undergo breast imaging for cancer screening, increasing the likelihood of incidental detection of otherwise asymptomatic nodules. Second, the larger volume of adipose and glandular tissue in the female breast could provide a more permissive environment for larval establishment, although direct evidence for sex-specific tissue tropism is lacking. Hormonal influences have also been proposed (7), and the absence of cases in children is consistent with that idea; however, many (29%, 11/38) of the women in our cohort were >55 years of age and likely postmenopausal (Table), which argues against a primarily estrogen-driven mechanism. Overall, ascertainment bias appears to be the most parsimonious explanation for the observed sex imbalance.
Our review shows that the clinical manifestation of breast dirofilariasis most commonly is a solitary, painless nodule that is clinically and radiologically indistinguishable from benign or malignant breast tumors. Reviewing 4 of the 10 cases with both imaging modalities reported, nodules were mammographically occult and detected only on ultrasonography, as we noted in the case we report from Israel. Thus, dirofilariasis should be considered even when mammography results are unremarkable, particularly in patients from or returning from endemic regions and reporting a focal breast nodule or with an incidental ultrasound finding of a hypoechoic nodule containing internal echogenic rod-like or coiled structures (30,36).
Preoperative diagnosis remains challenging. FNAC has limited diagnostic yield; few cases in our review achieved a parasitology diagnosis before surgery. Consequently, excisional biopsy remains the diagnostic and therapeutic standard.
Histopathologic examination typically demonstrates the characteristic morphology of Dirofilaria spp. nematodes, including a thick multilayered cuticle with external longitudinal ridges, paired reproductive tubes, and well-developed musculature (8). Ridge height and spacing differ between species but overlap sufficiently, and are distorted often enough in section, that species assignment from a sectioned worm is unreliable; an intact worm or microfilaria is needed for confident morphological identification (8,45,49). Molecular methods, mainly PCR with sequencing of cox1 and 12S rRNA, and of the ribosomal 18S and 28S genes and internal transcribe spacers 1 and 2 (39), provide definitive species identification and can be applied to FNAC specimens as well as to formalin-fixed paraffin-embedded tissue, although DNA recovery from fixed archival material is frequently poor (50; Appendix reference 1). Of note, molecular confirmation was reported in only 2 of 40 cases in our review. Therefore, species-level epidemiology of breast dirofilariasis is largely presumptive, and attributions were made from morphology, from the patient’s geographic origin, or from the organ involved, none of which is reliable where species ranges overlap and humans are accidental hosts. Although most cases in our cohort were morphologically attributed to D. repens nematodes, occasional reports of subcutaneous D. immitis infection in humans exist (Appendix reference 2), and broader use of molecular diagnostic testing could reveal that some cases historically attributed to D. repens were caused by D. immitis or related nematode species. Misattribution could run in either direction and is not restricted to D. repens and D. immitis nematodes. In North America, D. tenuis nematode is as likely a cause of subcutaneous disease as D. immitis, and in South and East Asia some cases attributed to D. repens nematodes might be D. asiatica, which is morphologically indistinguishable and is documented in dogs and in humans in coastal South India (2; Appendix reference 3). Thus, broader prospective molecular testing of subcutaneous Dirofilaria spp. infections at all anatomic sites is needed.
Because surgical excision is curative, systemic antiparasitic therapy is generally unnecessary. However, doxycycline, which targets the obligate Wolbachia bacterial endosymbiont, and ivermectin may have a role in the rare cases associated with documented microfilaremia or multiple lesions in which complete surgical excision is not feasible (1,6). In our cohort, despite undetectable microfilaremia, 2 case-patients from 1 report (38) received adjunctive ivermectin and doxycycline, and another case-patient (44) received adjunctive diethylcarbamazine. Systemic antiparasitic treatment is not supported by the current evidence for surgically excised, nonmicrofilaremic disease. No recurrences or major complications were documented after surgical excision in any patient included in our review.
The first limitation of this study is that review relied on case reports and small series published over 6 decades, and the depth of reporting was variable. Therefore, analyses were descriptive and used the available denominator for each characteristic, limiting comparisons across reports. Second, species attribution relied on morphology alone in 37 of 40 cases, so every species-level statement should be read as provisional. Finally, publication and ascertainment bias are likely substantial for geographic distribution and for female predominance. Most reports come from settings with widespread breast imaging, so the apparent concentration of cases in Europe and North America probably reflects ascertainment rather than true prevalence; underdiagnosis in resource-limited settings is likely.
Our review shows that breast dirofilariasis is an uncommon yet increasingly recognized manifestation of a mosquitoborne zoonotic infection. Further work is needed to delineate the host, vector, and parasite determinants of tissue tropism and to define the true epidemiology of this emerging zoonosis. Species-specific diagnosis should be made on the basis of molecular methods, and as those methods become more widely available, their use on minimally invasive samples (FNAC, core biopsy) could improve preoperative diagnosis and species identification.
Although the female predominance and unusual localization in our review could be partly explained by ascertainment bias, biologic factors warrant further investigation. Clinically, breast dirofilariasis frequently mimics malignancy, leading to unnecessary interventions and to avoidable patient anxiety. Clinicians and radiologists should be aware of dirofilariasis and consider parasitic etiologies in patients with a solitary breast nodule, especially in, or after travel to, Dirofilaria-endemic regions.