Myxoid variant of plexiform fibrohistiocytic tumor: case report

Introduction

Plexiform fibrohistiocytic tumor (PFH) is a rarely metastasizing slowly growing neoplasm usually affecting children and young adults with common predilection for the upper extremity, lower extremity, trunk, and head and neck. The tumor usually has a dermal-subcutaneous location, is poorly circumscribed, and is comprised, as the name implies, of a plexiform and/or multinodular proliferation of a variable admixture of fibroblasts or myofibroblasts and histiocytoid cells with a distinctive biphasic morphology (1-3). The (myo) fibroblastic component is usually arranged in fascicles while the histiocytoid component has a nodular or cannonball-like growth pattern with admixed osteoclast-type giant cells and variable hemorrhage set in a variably dense or hyalinized stroma with no evidence of nuclear pleomorphism, necrosis or increased mitotic activity. The spindle cells are usually smooth muscle actin (SMA) positive while the histiocytes are CD68 and CD163 positive. The molecular pathogenesis for this tumor is not well delineated so far. The tumor has a high local recurrence rate, around 40% especially if incompletely excised, and a low metastatic potential (4).

Myxoid change in PFH is extremely rare with only five cases of myxoid variant of PFH reported to date in the English literature (5-9). Being rare or underrecognized, myxoid change in PFH can represent a diagnostic pitfall. In this case report, the author describes a unique case of myxoid PFH encountered recently at her institution, discusses pitfalls inherent to the differential diagnosis and reviews the literature on this underreported entity. This article is presented in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-23-191/rc).

Case presentation

A 39-year-old male presented with a newly developed mass on his right forearm. Microscopic examination of the entirely excised mass revealed a multinodular poorly circumscribed dermal and subcutaneous proliferation of ovoid to spindle cells with prominent myxoid change (Figure 1A). The lesional cells demonstrated minimal atypia and were set within an extensively myxoid stroma with increased vascularity (Figure 1B). A small focus with biphasic morphology characterized by fascicular spindle cell arrangement admixed with histiocytoid foci arranged in a cannonball-like growth with occasional whirling (Figure 1C,1D) was noted. Osteoclast-like giant cells and focal hemorrhage were rarely seen in the histiocytoid areas. The mitotic index was low and there was no evidence of necrosis. Immunohistochemical stains were positive for SMA in the spindled myxoid areas with sparing of the histiocytoid nodules (Figure 2), and were negative for CD34, S100, p40, cytokeratin 5/6, cytokeratin AE1/AE3, desmin, CAM 5.2, ALK, smooth muscle myosin heavy chain, Melan A, HMB45, STAT6, myogenin, ERG, and MUC4. Fluorescence in-situ hybridization (FISH) was performed and was negative for ESWR1, DDIT3, USP6, and SYT gene rearrangements. FISH for MDM2 gene amplification was also negative.

Figure 1 Representative images of myxoid plexiform fibrohistiocytic tumor. (A) Low power view demonstrating the prominent myxoid nature of the tumor (hematoxylin & eosin, 4×); (B) foci with extensive myxoid change and increased vascularity (hematoxylin & eosin, 10×); (C) focal biphasic morphology showing fascicular spindle cell arrangement admixed with cannonball-like histiocytoid foci (hematoxylin & eosin, 10×); (D) higher power view of the histiocytoid foci with nodular cannonball-like growth (hematoxylin & eosin, 20×).

Figure 2 SMA immunostain highlighting the spindled myxoid areas with sparing of the histiocytoid nodules (10×). SMA, smooth muscle actin.

Overall, the histopathological features, particularly the focal biphasic tumor morphology with the presence of characteristic histiocytoid nodules, along with the immunohistochemical and molecular findings, helped in excluding other mimicking myxoid neoplasms and supported the diagnosis of myxoid PFH. As the tumor was completely excised with negative wide margins, additional surgical intervention was not necessary, and the plan was for the patient to be managed with close clinical follow-ups. To the author’s knowledge, the patient so far has not developed any local recurrence following the tumor’s complete excision.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Discussion

Myxoid variant of PFH has been described in very few case reports. To our knowledge only five cases to date have reported myxoid change in PFH in the English literature (5-9), and as such our understanding of this entity is somewhat tenuous. The significance of myxoid change in PFH is uncertain at this point in time. One theory by Chen et al. (6). proposed that the myxoid changes are a degenerative phenomenon in long standing PFH, while Cho et al. (7) suggested that myxoid PFH might represent a distinctive variant seen mainly in older patients. So far, a correlation between the presence of myxoid features in PFH and its behavior has not been elucidated yet. However, given the borderline nature of conventional PFH with its high local recurrence rate and low metastatic potential, the author assumes that the myxoid variant of PFH will retain this borderline nature with the caveat that more future studies are needed to better characterize the long-term clinical behavior of this variant.

The presence of prominent myxoid change in PFH is problematic as it may lead to an erroneous diagnosis particularly if common superficial myxoid neoplasms were to be considered. The differential diagnosis of superficial myxoid neoplasms is broad and includes myxofibrosarcoma, myxoid dermatofibrosarcoma protuberans (DFSP), myxoid liposarcoma, dedifferentiated liposarcoma, synovial sarcoma with myxoid change, solitary fibrous tumor with myxoid change, low-grade fibromyxoid sarcoma (Evans tumor), rhabdomyosarcoma, myxoid angiomatoid fibrous histiocytoma (AFH), nodular fasciitis with prominent myxoid change (10), cellular neurothekeoma (11) and angiofibroma of soft tissue (12).

Myxofibrosarcoma and myxofibrosarcoma-like dedifferentiated liposarcoma are characterized by elongated curvilinear blood vessels, abundant myxoid stroma and hyperchromatic or atypical spindled to stellate cells thus posing as potential mimickers to myxoid PFH. The absence of prominent atypia along with the focal presence of characteristic histiocytoid nodules with multinucleated giant cells and the negative FISH for MDM2 gene amplification basically excluded both diagnoses. Myxoid DFSP, solitary fibrous tumor with myxoid change, myxoid AFH and synovial sarcoma with myxoid change can have an overlapping morphology with variably cellular spindled cells set in a myxoid stroma associated with increased vascularity, a pattern similar to myxoid PFH; however, the absence of CD34, STAT6 and negative FISH for EWSR1 and SYT gene rearrangements argued against such entities. Bland spindled cells with whirling to storiform growth pattern, curvilinear blood vessels and abundant myxoid stroma, are typical features of low-grade fibromyxoid sarcoma. The absence of such typical features along with the negative MUC4 immunostaining helped in ruling this entity out. The absence of myogenic markers including desmin and myogenin and the bland nature of the lesional cells essentially excluded rhabdomyosarcoma. The absence of characteristic chicken-wire like vasculature and lipoblasts along with the negative FISH for DDIT3 gene rearrangement helped in excluding myxoid liposarcoma. USP6 gene rearrangement is commonly seen in nodular fasciitis with prominent myxoid change and its absence in this case helped in ruling it out. The tumor’s infiltrative pattern along with its focal biphasic morphology, cannonball-like histiocytoid foci and multinucleated giant cells argued against cellular neurothekeoma and angiofibroma of soft tissue.

In this case a thorough and complete ancillary testing along with careful morphologic search for characteristic histiocytoid nodules, the tumor’s eponymous histologic hallmark, played an important role in entirely excluding the aforementioned tumor considerations.

Conclusions

In conclusion, myxoid change in PFH is a rare phenomenon and a potential diagnostic pitfall. It is important to recognize this rare PFH variant and consider it in the differential diagnosis especially when encountered with a superficial myxoid neoplasm. Careful morphologic examination and search for focal classic areas of PFH is axiomatic to this diagnosis. Additionally, a thorough immunohistochemical and molecular ancillary testing are important diagnostic tools in reaching the right diagnosis and in ruling out other problematic mimickers.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The author has completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-23-191/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-23-191/prf

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-23-191/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Enzinger FM, Zhang RY. Plexiform fibrohistiocytic tumor presenting in children and young adults. An analysis of 65 cases. Am J Surg Pathol 1988;12:818-26. [Crossref] [PubMed]
2. Moosavi C, Jha P, Fanburg-Smith JC. An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the Armed Forces Institute of Pathology, in honor of Franz M. Enzinger, MD. Ann Diagn Pathol 2007;11:313-9. [Crossref] [PubMed]
3. Black J, Coffin CM, Dehner LP. Fibrohistiocytic tumors and related neoplasms in children and adolescents. Pediatr Dev Pathol 2012;15:181-210. [Crossref] [PubMed]
4. Luzar B, Calonje E. Cutaneous fibrohistiocytic tumours - an update. Histopathology 2010;56:148-65. [Crossref] [PubMed]
5. Liu CY, Lan J, Huang HY. Myxoid Plexiform Fibrohistiocytic Tumor Masquerading as Ganglion Cyst: A Case Report and Literature Review. Case Rep Pathol 2017;2017:5370894. [Crossref] [PubMed]
6. Chen L, Lin JH. Pathologic quiz case: supraclavicular subcutaneous nodule in a 24-year-old woman. Myxoid plexiform fibrohistiocytic tumor without multinucleated giant cells. Arch Pathol Lab Med 2004;128:931-2. [Crossref] [PubMed]
7. Cho S, Chang SE, Choi JH, et al. Myxoid plexiform fibrohistiocytic tumour. J Eur Acad Dermatol Venereol 2002;16:519-21. [Crossref] [PubMed]
8. Cho JH, Kim MY, Park YM, et al. A case of myxoid plexiform fibrohistiocytic tumor. Korean Journal of Dermatology 2005;43:1537-40.
9. Achach T, Moussa A, Hadhri R, et al. Myxoid plexiform fibrohistiocytic tumor without multinucleated giant cells. Ann Pathol 2007;27:317-9. [Crossref] [PubMed]
10. Amary MF, Ye H, Berisha F, et al. Detection of USP6 gene rearrangement in nodular fasciitis: an important diagnostic tool. Virchows Arch 2013;463:97-8. [Crossref] [PubMed]
11. Jaffer S, Ambrosini-Spaltro A, Mancini AM, et al. Neurothekeoma and plexiform fibrohistiocytic tumor: mere histologic resemblance or histogenetic relationship? Am J Surg Pathol 2009;33:905-13. [Crossref] [PubMed]
12. Mariño-Enríquez A, Fletcher CD. Angiofibroma of soft tissue: clinicopathologic characterization of a distinctive benign fibrovascular neoplasm in a series of 37 cases. Am J Surg Pathol 2012;36:500-8. [Crossref] [PubMed]