September 2013 Case 1

A 17 year-old with a left cheek mass

Sarah Ellison, MSIII, Matthew Szarko, M.D., H. James Williams, M.D.

Overview

A 17 year-old Caucasian female presented with a 3 month history of a slowly enlarging left facial cheek mass. On exam there was a 2 cm mass located in the mid-cheek which was tender to palpation, firm, and freely mobile. There was no history of trauma. The patient denied fevers, chills, and systemic symptoms. There was no overlying skin erythema or warmth. An area of skin dimpling just inferior to the mass was noted. A CT scan and ultrasound of the mass from a previous ED visit showed a 1.2 cm complex cystic structure in the superficial soft tissues of the left cheek. The patient was given a course of antibiotics which did not impact the size or tenderness of the mass.

Gross Description

The patient underwent excisional biopsy of the mass, which consisted of a 0.9 x 0.5 x 0.5 cm tan-pink-white nodule. Microscopically, the mass consisted of a well demarcated spindle cell proliferation within the subcutaneous soft tissues. The overlying epidermis was unremarkable with no connection to the underlying mass.

img1_500x329.jpg
The lesion was a highly cellular spindle cell proliferation running in fascicles and focally exhibited a storiform pattern.
img2.jpg (3)
Red blood cell extravasation and interspersed collagen were prominent features.
img3.jpg (3)
On high power, the spindle cells displayed uniform nuclei with occasional typical mitoses.
img4.jpg (2)
By immunohistochemistry, the spindled cells were positive for smooth muscle actin and negative for S-100.
img5.jpg (2)
SMA stain.

Diagnosis

What is the most likely diagnosis?

Answer

Please select an answer above.

Discussion

Nodular fasciitis (NF), also known in the past as pseudosarcomatous or infiltrative fasciitis, is a benign reactive proliferation of fibroblasts and myofibroblasts leading to a rapidly growing nodular mass in the subcutaneous tissue. The condition was first described by Konwaler et. al in 1955 as pseudosarcomatous fibromatosis [4] . NF is thought to be a reactive, reparative process as it histologically resembles granulation tissue [2,4]; however, it has been found to follow local trauma in only about 10-15% of patients [6]. More often NF is of idiopathic etiology, although an inadvertent activation of the soft tissue reparative process triggered by a mechanism other than trauma has been hypothesized [2]. It has been shown that the proliferating fibroblasts produce molecules involved in cytokine signaling and inflammation [1].

NF is characterized by rapid growth, usually presenting within a few weeks to months, which may lead to a misdiagnosis of a malignant soft tissue lesion [2,4,7]. Lesions are most commonly found in the subcutaneous tissue, but have also been reported in the dermis, deep fascia, and skeletal muscle [2,4,7]. NF is most commonly found on the forearm, but can also occur on the trunk, leg and face [2,5,7]. Around 7-20% of NF lesions occur in the maxillofacial region [3]. NF may occur at any age, but is most commonly found in the second through fourth decades [2,7].

Grossly, NF is similar to other soft tissue lesions and histologic examination is necessary for diagnosis. Gross examination commonly shows a non-encapsulated tan to grayish-white nodular mass, which has a characteristically small size of 2-3 cm. Only 8% are larger than 4 cm [2,6].

Histologic examination of NF reveals plump, spindle or stellate, immature-appearing fibroblasts arranged in a haphazard pattern in a background of myxomatous stroma and mucopolysaccharides. A spectrum exists between cellularity and collagen content, which varies from case to case [6,7,2]. Cases of NF always contain cytologically bland nuclei [5], in contrast to malignant lesions which may appear histologically similar except for their marked cytologic atypia. In addition, discrete nucleoli and abundant, typical mitotic figures can be seen. A mitotic rate of one mitotic figure per high power field has been found to be a reliable upper limit in NF [2]. The finding of atypical mitotic figures should prompt consideration of an alternate diagnosis [7]. Capillaries running in parallel fashion and red blood cell extravasation are features also commonly seen [7]. The reactive inflammatory component of NF consists of mononuclear cells, which are often found in the periphery of the lesion [2].

Shimizu et. al proposed a classification system for the different histologic types of NF in 1984: myxoid (Type 1), cellular (Type 2), and fibrous (Type 3). The different histologic types are thought to represent a progressive transformation [7]. Early lesions are predominantly myxoid, rich in mucopolysaccharides and mitotic figures, which transition to a highly cellular lesion with decreasing amounts of mitoses and mucopolysaccharides. The end-stage, fibrous type, of NF shows abundant collagen deposition [6].

The most important differential diagnosis is with malignant soft tissue sarcomas. In review of 53 cases of NF, Montgomery, et. al found that 43% were correctly diagnosed as NF while 21% were diagnosed as sarcoma. NF may be mistaken for a sarcoma due to rapid growth clinically with numerous mitoses and dense cellularity seen microscopically [6,5]. In contrast to the random arrangement of fibroblasts in NF, sarcomas usually have cells arranged in a more organized pattern, such as the herringbone pattern characteristic of fibrosarcomas [6]. The most important distinguishing feature favoring a sarcoma is cytologic atypia, including abnormal mitotic figures and hyperchromatic enlarged nuclei.

The immunohistochemical profile of NF may help differentiate from other lesions. NF characteristically stains positive for smooth muscle actin, muscle-specific actin, vimentin, and KP1 indicating myofibroblastic and histiocytic differentiation [5]. NF is characteristically negative for cytokeratin, S-100, and desmin. It is important to be aware that the immunohistochemical profile of NF can overlap with sarcomas. Muscle-specific actin is relatively non-specific and is found in a number of different sarcomas, particularly leiomyoma and leiomyosarcoma. Smooth muscle actin is more specific to smooth muscle and myofibroblasts [5].

In review of 134 cases of NF, Bernstein et. al studied found that NF was most commonly mistaken for inflammatory fibrous malignant histiocytoma [2]. Inflammatory malignant fibrous histiocytomas are more commonly greater than 4 cm in size and have an inflammatory component of neutrophils and plasma cells, not seen in NF [2]. NF can also be confused with benign dermatofibromas which display a storiform pattern. In contrast to NF, which is most commonly found in the subcutaneous tissue, dermatofibromas and inflammatory fibrous histiocytomas are most commonly found in the dermis and contain clusters of foamy histiocytes. Although extravasated red blood cells are commonly found in NF, hemosiderin should not be present. In contrast, hemosiderin can be seen in dermatofibromas and inflammatory malignant fibrous histiocytomas [7].

Treatment for NF consists of marginal excision. NF lesions almost never reoccur, and when they do the primary diagnosis should be scrutinized [2]. Berstein et. al found that in 134 cases of NF, 18 cases reoccurred after excision and in none of those cases were the original diagnoses supported on review of the original histology and clinical follow up [2].

NF is a benign lesion, but it is exceedingly important to correctly diagnose due to its ability to mimic other malignant soft tissue neoplasms. An initial diagnosis of a malignant lesion in a patient with NF may cause unnecessary treatment and psychologic distress. In contrast, a diagnosis of NF when a true malignant neoplasm exists can lead to a delay in treatment with increased morbidity. Therefore, correct identification and diagnosis of NF is exceedingly important, despite the benign clinical course of the lesion.

References

  1. Bacac M, Migliavacca E, Stehle JC, et al. A gene expression signature that distinguishes desmoids tumours from nodular fasciitis. J Pathol. 2006;208:543-553.
  2. Bernstein KE, Lattes R. Nodular (pseudosarcomatous fasciitis), a nonrecurrent lesion: clinicopathologic study of 134 cases. Cancer. 1982;49:1668-1678.
  3. Han W, Hu Q, Yang X, et al. Nodular fasciitis in the orofacial region. Int J Oral Maxillofac Surg. 2006;35:924-927.
  4. Konwaler BE, Keasbey L, Kaplan L. Subcutaneous pseudosarcomatous fibromatosis (fasciitis). Am J Clin Pathol. 1955;25:241-252.
  5. Montgomery EA, Meis JM. Nodular fasciitis: its morphologic spectrum and immunohistochemical profile. Am J Surg Pathol. 1991;15:942-948.
  6. Rosenberg, AE. Pseudosarcomas of Soft Tissue. Arch Pathol Lab Med. 2008;132:579-586.
  7. Shimizu S, Hashimoto H, Enjoji M. Nodular fasciitis: an analysis of 250 patients. Pathology. 1984;16:161-166.
  8. Weiss, SW and Goldblum, JR. Enzinger & Weiss's Soft Tissue Tumors, 5th ed. Philadelphia, PA: Mosby Elsevier, 2008.
  9. Zuber TJ, Finley JL. Nodular fasciitis. South Med J. 1994;87:842-844.