A facial mass with "bag-of-worms" appearance - Clinical Advisor

A facial mass with “bag-of-worms” appearance

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A 30-year-old healthy Hispanic woman presents with a slowly progressive facial deformity present since early childhood. She denies any new lesions during this time, any history of trauma to the area, and any family history of similar skin lesions. Examination reveals a bulging, deformed dermal mass with a “bag-of-worms” appearance involving the upper right quadrant of her face, with hypertrophy of the overlying skin and soft tissues. Neurofibromas and café-au-lait macules are not observed. 

 

Plexiform neurofibromas (PNFs) are rare, benign, peripheral nerve sheath tumors composed of a variable mixture of Schwann cells, perineural elements, fibroblasts, and hematopoietic cells in a collagenous or myxoid stroma.1-3 These lesions typically present at birth or during the first...

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Plexiform neurofibromas (PNFs) are rare, benign, peripheral nerve sheath tumors composed of a variable mixture of Schwann cells, perineural elements, fibroblasts, and hematopoietic cells in a collagenous or myxoid stroma.1-3 These lesions typically present at birth or during the first years of life; however, a few cases of late-onset PNFs have also been described.1,3 Depending on their location and size, they may be cosmetically unacceptable.4 In addition, PNFs have the potential to transform into malignant peripheral nerve sheath tumors, which is the most common cause of mortality.4

The exact pathogenesis of PNFs is unclear. Trauma is thought to be an inciting factor, although no clear associations have been made.5 Another theory involves the secretion of high concentrations of stem cell activators by tumorigenic Schwann cells, which activates mast cells to release inflammatory cytokines, further stimulating these Schwann cells and the surrounding fibroblasts and blood vessels.2

Although PNFs are commonly associated with neurofibromatosis type 1 (NF1), they are not pathognomonic.2,6 Regardless, their presence should prompt search for other stigmata of NF1, including >5 café-au-lait macules, >1 neurofibroma or ≥1 PNF, intertriginous freckling, optic gliomas, >1 Lisch nodule, a distinctive osseous lesion (including dysplasia of the sphenoid bone or thinning of the long bone cortex), and a first-degree relative with NF1.5 Presence of ≥2 of these criteria described by the National Institutes of Health is diagnostic of NF1.5

Clinically, PNFs appear as ill-defined, subcutaneous, or dermal masses commonly located in the head and neck region.2,4,7 Because they arise from multiple nerves as bulging and deforming masses involving the connective tissue and skin folds, PNFs are often described as having a “bag of worms” appearance.4,7

Although all peripheral nerves are susceptible to PNF formation, there is a predilection for the larger peripheral nerves of the face, neck, and extremities.5 Some lesions may be only a few centimeters in diameter, whereas others may affect an entire limb, resulting in a phenomenon called elephantiasis neuromatosa.5 Lesions exhibit increased growth rates during childhood and periods of hormonal change.5 Some patients may also have pain, aesthetic problems, and neurologic involvement, depending on the location.7 PNFs may also induce hypertrophy and pigmentary changes of overlying skin and soft tissue, and, in some cases, may change the surrounding osseous architecture.5

Diagnosis of PNF is based on clinical features, although histopathology can be useful to exclude malignant transformation.4 On histology, neurofibromas consist of small, bland, elongated spindle cells with characteristic wavy or comma-shaped nuclei in a myxomatous stroma.5 Unlike schwannomas and other forms of neurofibromas, PNFs are unencapsulated and involve several nerve fascicles.5 Positive immunohistochemical staining for S100 protein can differentiate this neurogenic sarcoma from other sarcomas.5 Radiologically, PNFs appear as large, round masses consisting of numerous neurofibromas, referred to as the “central dot sign,” and diffuse thickening of the involved nerve, often with extension into nerve branches.6

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The differential for PNFs includes schwannomas and other forms of neurofibromas, which may be distinguished via histology as described, synovial sarcomas, other types of soft tissue sarcomas; these, in turn, may be distinguished via immunohistochemistry, and synovial sarcomas, which often demonstrate mineralization with calcification—a histologic finding not present in PNF.5

Definitive treatment requires complete surgical resection. Unfortunately, PNFs tend to recur despite an appropriate resection, especially in younger patients and when they involve the head and neck region.4,5,7 Their tendency to bleed profusely with surgical removal often makes complete resection difficult.7 Imatinib treatment may be useful in reducing tumor volume, especially in cases of unresectable, progressive, and symptomatic lesions.3 Finally, all patients with PNFs require serial follow-ups to monitor for the development of malignant peripheral nerve sheath tumor, which may be asymptomatic until distant metastases occur.1

In our case, the patient declined surgery and chose to undergo clinical follow-up every 6 months. 

Melinda Liu, BA, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.

References

  1. Chieng GH, Bhatnagar A, Mirza M. Solitary plexiform neurofibroma, a pitfall in diagnosis of lipoma. BMJ Case Rep. 2010 Sep 20. doi: 10.1136/bcr.01.2010.2696
  2. Huang W, Chong WS. Facial plexiform neurofibroma: is it truly just skin deep? BMJ Case Rep. 2013 Oct 7. doi: 10.1136/bcr-2013-200716
  3. Jungmann J, Heydt C, Bohle R, Pföhler C, Vogt T, Müller CS. Genetic basis of a solitary familial plexiform neurofibroma without verified associated neurofibromatosis. J Dtsch Dermatol Ges. 2016;14:525-527.
  4. Tchernev G, Chokoeva AA, Patterson JW, Bakardzhiev I, Wollina U, Tana C. Plexiform neurofibroma: a case report. Medicine (Baltimore). 2016;95:e2663.
  5. Blitz NM, Hutchinson B, Grabowski MV. Pedal plexiform neurofibroma: review of the literature and case report. J Foot Ankle Surg. 2002;41:117-124.
  6. Cebesoy O, Tutar E, Isik M, Arpacioglu O. A case of isolated giant plexiform neurofibroma involving all branches of the common peroneal nerve. Arch Orthop Trauma Surg. 2007;127:709-712.
  7. Mishra PK, Dwivedi R, Shrivastava DC, Gaur SC. Isolated plexiform neurofibroma of arm with unusual presentation — a rare case report. J Clin Diagn Res. 2015;9:RD03-RD04. doi: 10.7860/JCDR/2015/10530.5407

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