Proliferative funiculitis is a benign, reactive, spindle cell proliferation composed by fibroblasts and myofibroblast of the spermatic cord resembling fasciitis-like lesions.
Proliferative funiculitis arises in males.
Some patients were treated with orchidectomy (Hollowood and Fletcher 1992; Michal et al. 2008; Sallami et al. 2012), while in other cases only incisional biopsies or incomplete or marginal excision were performed (Hollowood and Fletcher 1992; Michal et al. 2008; Shintaku and Ukikusa 2003).
Even if the lesion presents ill-defined margins, it does not behave in an aggressive fashion. Apart from one recurrence (Hollowood and Fletcher 1992), patients show no signs of repetitive or metastatic disease.
At low power, the lesion is paucicellular to moderately cellular, and consists of a spindle cell proliferation with fibroblastic or myofibroblastic features. Cells are arranged in an haphazard fashion, occasionally forming loose fascicles with a vague storiform appearance, set in a loose collagenous or myxoid stroma (Hollowood and Fletcher 1992; Michal et al. 2008; Sallami et al. 2012; Shintaku and Ukikusa 2003). The lesion is usually circumscribed, even if a true fibrous capsule is not always found (Shintaku and Ukikusa 2003). The lesion has the tendency to infiltrate the surrounding tissue of the normal spermatic cord, even if the behavior is benign (Hollowood and Fletcher 1992).
At higher magnification, cells have plump, oval to fusiform, sometimes vesicular nuclei, basophilic nucleolus, and a variable amount of cytoplasm, which may be both thin, tapering, and eosinophilic or plump and amphopilic (Hollowood and Fletcher 1992). In some cases, a second population of giant cells, which are similar to those found in proliferative fasciitis, can be present. Indeed, these cells are larger and more basophilic than the main population, with oval nuclei and prominent eosinophilic nucleoli (Hollowood and Fletcher 1992; Michal et al. 2008).
In the background, the lesion shows medium-sized, thin-walled blood vessels, even though cases with prominent vascularization have been described, and a small amount of lymphocytes are always found within the lesion, occasionally with a follicle-like architecture (Hollowood and Fletcher 1992; Shintaku and Ukikusa 2003).
Mitotic count is usually around one per ten high-power fields (HPF) and it is possible to find moderate pleomorphism and atypia (Hollowood and Fletcher 1992; Michal et al. 2008; Sallami et al. 2012; Shintaku and Ukikusa 2003). Occasionally, some bizarre cells are found (Shintaku and Ukikusa 2003). Rarely, the lesion may be more cellular, with aggregates of plump spindle cells with fusiform nuclei, foci of hyalinization, and with the presence of both large vascular spaces and small blood vessel with circumferential fibrosis. In these areas, mitotic count may reach two per ten HPF, without abnormal forms (Hollowood and Fletcher 1992). In one case, numerous mast cells were found in the background of the lesion (Shintaku and Ukikusa 2003).
Some cases of proliferative funiculitis present a proliferation of both epithelioid and epithelial cells arranged in glandular structures, often situated in the deep portion of spermatic cord stroma, called mesothelial glandular proliferation (MGS) (Michal et al. 2008). In such lesions, the spindle cells change their morphology and become plump and epithelioid, sometimes reaching a genuine epithelial appearance. They are arranged in linear fashion, sometimes in cords and in small glandular structures. In some cases, a typical zonal arrangement of different cells is found: a central necrotic area with spindle cells proliferation that turns into epithelioid type in the periphery.
Spindle cells of proliferative fasciitis usually show positivity for vimentin, smooth muscle actin (SMA) and muscle specific actin (HHF35) (Hollowood and Fletcher 1992; Michal et al. 2008; Shintaku and Ukikusa 2003).
In cases of proliferative funiculitis associated with MGS, both spindle and epithelioid cells stain positive for cytokeratin AE1/AE3 and for SMA, while CAM 5.2 stains epithelial cells and cytokeratin CK 5/6 and EMA stain the glandular structures. Desmin stains myofibroblasts, while glandular structures are negative. S100 protein, CD34, and CD117 are usually negative.
Proliferative funiculitis may be confused with several malignant mesenchymal tumors, including embryonal rhabdomyosarcoma, leiomyosarcoma, myxofibrosarcoma and dedifferentiated liposarcoma, as well as from locally aggressive tumors such as desmoid fibromatosis. The predominant reactive/inflammatory nature of proliferative funiculitis and the absence of atypia and of brisk mitotic activity, including atypical mitoses, help to exclude malignancy. An appropriate panel of immunohistochemical markers, including muscle markers, MDM2 and beta catenin is a useful complement. In cases of proliferative funiculitis associated with MGS, the differential diagnosis includes metastatic adenocarcinoma and mesothelioma (Michal et al. 2008).
References and Further Reading
- Konstantinov, A. S., & Shelekhova, K. V. (2018). Proliferative funiculitis-like dedifferentiated liposarcoma with mesothelial glandular structures: A diagnostic pitfall. International Journal of Surgical Pathology. https://doi.org/10.1177/1066896918820443.