Proliferative Funiculitis-Like Dedifferentiated Liposarcoma With Mesothelial Glandular Structures: A Diagnostic Pitfall

We present a case of dedifferentiated liposarcoma of the spermatic cord with focal mesothelial proliferation that was initially misdiagnosed as proliferative funiculitis with mesothelial glandular structures because of similar morphology. A 66-year-old man was referred to our oncology center with pain and discomfort in the left part of the scrotum. A manual examination revealed a firm, painless nodule measuring 2.5 × 1.5 cm in the left spermatic cord. A magnetic resonance imaging evaluation confirmed the diagnosis of a solid ovoid tumor that was 2.4 × 3.4 × 2.6 cm and had sharp borders and an actively accumulating paramagnetic signal. The patient underwent excision of the lesion, which grossly presented as a gray-white nodule that was 4.5 × 4 × 3 cm with a firm consistency and was adhered to the spermatic cord. Histologically, the lesion was composed of irregular, spindle cell fibroblast/myofibroblast-like proliferative cells that were arranged in a haphazard fashion and focally forming cellular fascicles (Figure 1A). In a few places, the storiform arrangement of cells was interrupted by areas with more pronounced cellularity and an admixture of giant multinucleated cells (Figure 1B). Mild nuclear atypism was observed. The stroma was prominently vascularized, with thin-walled capillary-type vessels. The mitotic rate did not exceed 2 per 10 high-power fields, although in more cellular parts, there were 5 mitotic figures per 10 high-power fields. No atypical figures were noted. Single spindle cells were immunoreactive for smooth muscle actin; however, the cells were negative for STAT6, S100, and AE1/3. Among the predominant spindle cell proliferation, small complexes of epithelial cells grouped in glandular structures were found to be immunohistochemically stained by cytokeratin AE1/3, EMA, D2-40, and calretinin, in contrast with a fibroblastic-like background, which confirmed their mesothelial nature (Figure 1C).

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Figure 1.

(A) Primary lesion: diffuse, loosely fascicular, and fasciitis-like proliferation of spindle cells (hematoxylin-eosin [H&E], 10×). (B) Primary lesion: more cellular areas of the lesion showing admixture of giant multinucleated cells (H&E, 20×). (C) Mesothelial glandular structures highlighted by calretinin (insert) against a myofibroblast-like background in the primary lesion. (D) Recurrent tumor (H&E, 10×). (E) Atypical cells in loose, myxoid stroma. Peripheral area of the recurrent tumor (H&E, 10×). (F) Immunohistochemical staining for MDM2 (note the absence of a reaction in the mesothelial structure [arrow]). Fluorescence in situ hybridization demonstrates MDM2 gene amplification.

Considering the lack of cytologic atypia, the brisk mitotic activity, and the absence of gross appearance suggestive of a malignant tumor, the lesion was classified as pseudosarcomatous proliferative funiculitis with mesothelial glandular structures as described by Michal et al. ¹

Six months later during monitoring with magnetic resonance imaging, a recurrent lesion was found. A left side orchifuniculectomia revealed a solid, gray-white, poorly circumscribed mass 3 × 2.5 × 2 cm in size that had replaced much of the lower portion of the spermatic cord without involvement of the testis. Histopathologically, the tumor was composed of highly atypical hyperchromatic spindle and giant cells arranged in haphazard cellular fascicles (Figure 1D). At the periphery of the lesion, there was a small region with a myxoid background (Figure 1E). The mitotic rate was low, similar to that in the primary lesion, although abnormal mitotic figures were readily noted. The recurrent behavior of the high speed of growth and prominent cell atypia raised doubts regarding the initial diagnosis of the reactive lesion, and sarcoma was suspected. More precise investigations of the slides from the primary and recurrent tumors revealed small foci of intermixed, noncompressed fat at the outer portions of the lesions. Immunohistochemical staining with an antibody against MDM2 showed strong positive nuclear expression. The diagnosis of dedifferentiated liposarcoma was confirmed by fluorescent in situ hybridization, which highlighted amplification of the MDM2 gene in both samples (Figure 1F).

This case highlights that dedifferentiated liposarcoma can closely resemble reactive lesions and that such morphological phenomena as mesothelial proliferation within pseudosarcomatous proliferative funiculitis, as described by Michal and colleagues in 2008, can also occur in tumors of the spermatic cord.^1,2

The most common sarcoma of the paratesticular tissues in adults is liposarcoma, which represents 46% of all malignant tumors involving the spermatic cord. ³ Histologically, liposarcomas of this region display the spectra observed elsewhere. The most common subtypes are well-differentiated and myxoid. Dedifferentiated liposarcomas may be seen less often. ⁴

The initial presentation of this case did not show any evidence of malignancy, and the sarcomatous appearance become apparent only in the recurrent tumor. Local recurrence is the main problem of paratesticular sarcoma, which may occur after a delay of up to 5 years. ⁵ There is a possibility of proliferative funiculitis recurrence if it is not completely excised. However, these lesions are nonmetastasizing, in contrast to liposarcoma. Therefore, a differential diagnosis is crucial for the patient. Careful histological examination coupled with immunohistochemical and molecular studies can help in making a differential diagnosis of sarcoma and reactive process.