Department of Pathology, University of Oklahoma Health Sciences Center
June 2004, Case 406-2.
A 50 year-old woman with a breast mass
O. Hans Iwenofu, M.D., Zoltan G. Laszik, M.D., Ph.D. Last update: May 30, 2004.
Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma.
Clinical information: The patient was a 50 year-old African American woman with. A mass in her left breast was detected on mammogram and palpation. A needle biopsy was performed and an excision followed. The specimen was 6.5 x 5.5 x 1.5 cm and contained a 1.8 x 1.0 x 1.0 cm vaguely circumscribed, pale, tan lesion that is free of necrosis. The followings are representative sections obtained from the lesion.
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|DIAGNOSIS: Inflammatory myofibroblastic tumor (pseudotumor).|
Pathology of the case:
On microscopic examination, the salient pathologic feature is a cellular lesion with pushing margins that is well circumscribed by the surrounding mature adipose tissue (Panel A and B). The cellular lesions appear to be spindly that is decorated with some thick collagen fibers (Panel C). Epithelium line spaces representing the entrapped ducts and glands of the mammary glands are also present (Panel C, D, and E). Patches of chronic inflammatory cell infiltration are also present (Panel D, and E). On high magnification, the spindle cells are bland and intermingled with thick collagen bundles. The chronic inflammatory cell infiltration is composed predominantly of mature lymphocytes admixed with small number of plasma cells and occasional eosinophils (Panel G and H). Occasional foreign body type giant cells can be found (Panel G). On immunohistochemistry, the entrapped epithelial components are strongly positive for cytokeratin AE1/AE3.
Discussion: General Information Pathology Differential diagnosis
Inflammatory myofibroblastic tumor (IMT) also known as inflammatory pseudotumor, plasma cell granuloma, xanthomatous pseudotumor, pseudosarcomatous myofibrohistiocytic proliferation is a tumor of uncertain origin usually seen in the lung and airways of young patients. 1 Many reported cases of this entity occur in the lung but it has been reported in extrapulmonary sites including the gastrointestinal tract, retroperitoneum, urinary tract, peritoneum, mesentery, pancreas, spinal cord meninges, intracranial spaces, liver, thyroid, spleen and lymph nodes 1.
IMT of the breast is a very rare entity. The first case was reported by Pettinato et al 2 and since then less than twenty cases have been reported in the literature. To this date, the exact nature of this entity remains an enigma. Although it is considered by some investigators to be reactive and inflammatory in nature there is emerging evidence of clonality and cytogenetic changes hence supporting the neoplastic nature of this lesion 3. Indeed the recent finding of ALK expression as a result of chromosomal translocation involving 2p23 was recently demonstrated in some of these tumors 4, 5.
Clinically, most of the reported cases presented with a palpaple discrete, mobile, slightly tender mass and most adhered to the overlying skin. The size ranged from 2 - 4cm in diameter. Skin ulceration portends a malignant neoplastic process. IMT occurs mainly in children and young adults though it may occur in either sex and at any age 6, 7, 1, 2.
Histologically, IMT is composed of fascicles of spindle cells admixed with mature plasma cells, lymphocytes, histiocytes and foamy macrophages 8, 2. The lesion is cellular but the spindle cells do not exhibit significant pleomorphism or other sinister features of a malignant neoplasm. The cellularity can show tremendous variability even within the same lesion. High cellularity featured by a preponderance of inflammatory component is often seen in early phase. The mature lesions are less cellular and contain collagen bundles. The spindle cells have been shown to be myofibroblasts by immunohistochemical and ultrastructural studies 9, 10, 2. Typically, the spindle cells are immunoreative for vimetin and smooth muscle actin with rare positivity for cytokeratin and desmin in the a smaller proportion of cases 11, 12, 3. Occasional cells may be positive for S100 protein.
Most cases of IMT follow a benign course. However, a few cases with more aggressive behavior have progressed into soft tissue sarcoma with metastases after several recurrences and have been referred to as “inflammatory fibrosarcoma”. This entity should be considered as “soft tissue neoplasm with low malignant potential”.13, 14 This rather uncommon but unpredictable behavior ask for regular follow up after resection.
The differential diagnoses include a long list of low-grade spindle cell lesions with inflammatory cells. The more commonly encountered malignant entities that would be confused with IMT include ones include plasmacytoma, metaplastic (sarcomatoid) carcinoma, fibrosarcoma and other sarcomas with inflammatory infiltration, fibromatosis, and Hodgkin's lymphoma.
Plasmacytoma with infiltration into the surrounding tissue may mimic inflammation. The atypical plasma cells should raise the suspicion. A high level of nuclear pleomorphism and other sign of malignant behavior such as frequent mitotic figures and necrosis would suggest a malignant neoplasm such as fibrosarcoma with inflammatory changes.
Metaplastic carcinoma (sarcomatoid carcinoma) often present as spindle cell tumors in organs where carcinomas are frequently seen. Careful search for genuine epithelial component as well as positive immunoreactivity for cytokeratin should help distinguishing this entity from IMT.
Fibrosarcoma and other sarcomas with inflammatory infiltration usually display a much higher degree of cytologic atypia. Other signs of sinister nature such as necrosis are also present in fibrosarcoma but not IMT.
Fibromatosis has irregular, infiltrating margins and is composed of rather fascicles and bundles of spindle cells. The lesion can range from cellular to rather collagenized. Similar to IMT, there are also entrapped ducts and lobules. In contrast, there is a lack of the inflammatory changes in fibromatosis.
Hodgkin's lymphoma occurring in an extranodal sites and particularly in older patients may look atypical. The mixed inflammatory background and occasional cells with atypia may therefore suggest Hodgkin's lymphoma. Immunohistochemical studies are often helpful in separating the two entities.
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