Recently, we collaborated with Zhao Ming from the Department of Pathology and Meng Xuli from the Department of Breast Surgery, Zhejiang Provincial People's Hospital, to test 2 cases of female breast nodular fasciitis, emphasizing the value of FISH detection of USP6 gene translocation in the diagnosis and differential diagnosis and summarizing and analyzing in combination with related literature, which was published in the Experimental and Molecular Pathology.
Nodular fasciitis (NF) is a self-limiting, pseudosarcomatous benign mesenchymal tumor of fibroblastic/myofibroblastic origin occurring mainly in the subcutaneous soft tissues of young and middle-aged people. Its molecular genetics is characterized by a recurrent USP6 gene translocation. Nodular fasciitis involving the breast is very rare and only a few cases have been reported in the literature. Breast NF can be clinically, radiologically, and histologically confused with malignancy, posing a significant diagnostic challenge to clinicians, radiologist, and pathologists.
The most common site of nodular fasciitis is the upper extremities, followed by the head and neck and trunk. Cases occurring in the breast are very rare and only a few cases have been reported in the literature. Due to its rapid growth, infiltrative mass appearance on imaging, and histologically variable, often cellular and significant nuclear division activity, nodular fasciitis occurring in the breast is often suspected to be malignancy, especially in the puncture diagnosis. In recent years, molecular genetics has shown that nodular fasciitis is associated with a recurrent USP6-MYH9 gene fusion, leading to the formation of a t(17;22)(p13;q13) chromosome translocation, suggesting a clonal tumor abnormality in nature. The detection of USP6 translocations by FISH fracture probes is a very useful clinical tool for the diagnosis of nodular fasciitis.
The authors share two cases of nodular fasciitis of the breast. Case 1 is a healthy 29-year-old woman who incidentally discovered a solid painless nodule in her left breast without skin retraction or nipple and areola abnormalities during a routine annual physical examination and with no history of trauma. Her past medical history and family history are free of malignancy. Ultrasonography revealed a 0.8 cm, irregularly shaped, markedly hypoechoic nodule on the upper outer quadrant of the left breast with indistinct borders and internal blood flow distribution. The lesion was classified as 4-B by BI-RADS and was clinically suspicious for malignancy. Case 2 is a previously healthy 55-year-old woman who self-detected a palpable and painless mass in the lower inner quadrant of the right breast. There was no axillary lymph node enlargement and no history of trauma. Magnetic resonance imaging (MRI) revealed a 1.1 x 0.6 cm oval nodule with well-defined margins and equal to low signal on high signal T2-weighted and T1-weighted imaging. Dynamic contrast-enhanced MRI showed rapid early enhancement and a washout pattern on the time-signal intensity curve, and the lesion was evaluated as a BI-RADS category 4-A.
Excisional biopsies were performed for the two patients. Microscopically, the two lesions exhibited similar features. The lesions were unencapsulated and both showed at least one focal infiltrative border. In case 2, the tumor cells extended focally into the surrounding breast parenchyma. The 2 tumors had a moderate cell density with a uniform distribution of spindle cells which are arranged in short crossed bundles and storiform pattern, located in a mucinous to collagenous stroma with scattered lymphocytic infiltrates. Nuclear division images could be seen, but no atypical nucleated division images were observed. Both tumors showed diffuse strong positive SMA and CD10 immunohistochemical expression. All other IHC targets including cytokeratin 5/6, AE1/3, p63, desmin, S100 and β-catenin (nuclear) were negative. As nodular fasciitis of the breast was suspected, FISH detection of USP6 fracture was performed. 100 non-overlapping nuclei in a "hot spot" area rich in tumor cells were evaluated, and 15% or more of the cells were found to be positive when isolated. Both cases showed significant USP6 gene splitting (23% and 25%, respectively), thus confirming the diagnosis of mammary nodular fasciitis. Both patients were in good condition, with no recurrence at 23 and 12 months of follow-up, respectively.
A discussion ensued among the authors, some of the main points of which are summarized here:
(1) Although nodular fasciitis of the breast is classified as one of the benign mesenchymal tumors of the breast in the fifth edition of the WHO classification, its incidence is rare. Recent literature shows that only Paliogiannis et al. summarized 22 cases of nodular fasciitis of the breast reported in the literature during 1990-2016. During 2004-2014, the largest number of single-center diagnoses was reported by Lu et al. from the Department of Pathology, Fudan University Shanghai Cancer Center, who reported 272 cases of nodular fasciitis of the breast, 9 of which were located in the breast, with an incidence of 3.3%.
(2) Nodular fasciitis of the breast has the same histomorphology as nodular fasciitis occurring at other sites. Microscopically, the lesion is generally well-defined but unencapsulated, usually with a focal infiltrative border, occasionally interspersed with intrinsic mammary ducts and lobules. It consists of fibroblasts and/or myofibroblasts with no apparent cytologic heterogeneity or pleomorphism and can be divided into three histologic subtypes, including mucinous, cellular, and fibrous, depending on the stromal characteristics and cytoarchitecture of the lesion cells. A tissue culture structural pattern with erythrocyte extravasation and lymphocytic infiltration is typical of the lesion, but areas rich in cells may have a fascicular or storiform growth pattern.
(4) Because of its rarity, nodular fasciitis occurring in the breast has only recently been widely reported. Cloutier et al. (2021) reported 12 cases of nodular fasciitis of the breast, of which 9 (75%) were found to be associated with USP6 translocations by RNA sequencing, 4 (50%) were USP6-MYH9 fusions, and the other 4 had other genes as the partner genes, including CTNNB1, NACA, SLFN11, and LDHA, and this study also expands the molecular genetic lineage of nodular fasciitis.
(5 It is worth mentioning that Prof. Zhang Hongying et al. (2021) from West China Hospital also reported 7 cases of nodular fasciitis of the breast, of which 6 cases were associated with USP6 translocations and 2 cases had MYH9 as the partner gene (verified by FISH and RT-PCR).
(6) Due to the rarity of its site of occurrence, the pathologic diagnosis of nodular fasciitis of the breast is challenging and may tend to be over-diagnosed as a malignant spindle cell tumor of the breast. Differential diagnostic considerations include metaplastic/spindle cell carcinoma, mesenchymal predominant phyllodes tumor, dermatofibrosarcoma protuberans, aggressive fibromatosis, myofibroblastic tumor, and low-grade malignant fibromyxoid sarcoma.
(7) It is particularly worth emphasizing that adequate sampling is necessary, as some of the diagnostic morphologic features may be missed in small puncture samples.
References
(1) Zhao M，et al. 2021. Nodular fasciitis of thebreast: Report of two cases illustrating the diagnostic implications for USP6gene rearrangement and brief review of the literature. Experimental andMolecular Pathology. 123: 104690.
(2) PaliogiannisP et al. 2016. Breast nodular fasciitis: a comprehensive review. Breast Care(Basel). 11:270-274.
(3) Lu L et al.2015. Nodular fasciitis: a retrospective study of 272 cases from China withclinicopathologic and radiologic correlation. Ann. Diagn. Pathol. 19:180-185.
(4) Cloutier JM, et al. 2021. Nodular fasciitis of the breast:clinicopathologic and molecular characterization with identification of novelUSP6 fusion partners. Mod Pathol. 2021 Jun 7. doi:10.1038/s41379-021-00844-4.
(5) Zhang YH etal. 2021. Nodular fasciitis of the breast: a clinicopathological and geneticanalysis of seven cases. Zhonghua. Bing. li. Xue. Za. Zhi. 50, 476-481.Chinese.
