Mammary-type myofibroblastoma of the liver: multi-modality imaging features with histopathologic correlation.

A 46-year-old woman with an incidentally discovered hepatic mass at the time of echocardiography underwent additional imaging for characterization. Ultrasound demonstrated a 5.3 cm solid hyperechoic mass. Computed tomography and magnetic resonance imaging showed intratumoral fat and nodular foci of progressive enhancement. The patient underwent surgical resection, with the mass demonstrating histopathologic and immunohistochemical features diagnostic of a hepatic mammary-type myofibroblastoma. We present herein the clinical, imaging, and pathologic features in this unique case of hepatic mammary-type myofibroblastoma. Mammary-type myofibroblastoma is a benign spindle cell tumor typically composed of groups of myofibroblasts within bands of hyalinized collagenous stroma. Some tumors also have an adipocytic component. The tumor is nearly exclusively seen in the breast and although extramammary soft tissue locations have been described, to our knowledge, this is the first reported case in the liver or any visceral site. Although rare, radiologists and clinicians should, therefore, be aware of the possibility of a mammary-type myofibroblastoma when a solid, non-encapsulated, fat containing tumor in the liver is encountered.

Radiological and histopathological features of hepatic inflammatory myofibroblastic tumour: analysis of 10 cases.

AIM: To evaluate the radiological and histopathological features of hepatic inflammatory myofibroblastic tumours (IMTs), and improve the understanding of this tumour. MATERIALS AND METHODS: A retrospective analysis of radiological and histopathological features of 10 cases of IMT was carried out from May 2003 to September 2011 at the Second Xiangya Hospital of Central South University. RESULTS: Ten cases (five male and five female patients; age range 4-68 years) were enrolled. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed that the lesions were regular, hypodense or hypointense (T1WI) masses with well-defined borders (n = 8) or ill-defined borders (n = 2). The maximum diameter ranged from 3.1-13.4 cm (mean = 6 cm). The masses showed homogeneous (n = 8) or inhomogeneous (n = 2) density. Contrast-enhanced CT and MRI showed the lesions were mildly, irregularly enhanced (n = 7) or not enhanced (n = 2) in the arterial phase and markedly enhanced in the portal venous phase or delayed phase. Hepatic arteriography revealed that the lesions were hypovascular and had a well-defined border. One patient had lung metastasis with obvious arterial phase enhancement. None of the patients had a history of hepatitis, cirrhosis, or enlarged lymph nodes. Pathology showed that the gross appearance of the tumours was smooth. The tumour cells comprised spindle-shaped fibroblast and myofibroblast cells with abundant inflammatory cells. Immunohistochemistry showed that most were positive for vimentin, smooth muscle actin (SMA), and CD68, but negative for CD34, anaplastic lymphoma kinase (ALK), S-100, and CD117. CONCLUSION: Radiological features of IMT have some characteristics of an intermediate-grade malignant tumour. However, imaging alone cannot be used to diagnose IMT. Therefore, histopathological examination is necessary for confirmation.

[Clinicopathologic study of sinonasal inflammatory myofibroblastic tumor].

OBJECTIVE: To study the clinicopathologic features, immunophenotype and ultrastructural features of sinonasal inflammatory myofibroblastic tumors (IMT). METHODS: The clinical and histologic features of 5 cases of sinonasal IMT were reviewed. Immunohistochemical study for vimentin, MSA, SMA, calponin, h-caldesmon, desmin, ALK, fibronectin, CK, S-100 and Ki-67 was carried out. Ultrastructural examination was also performed in two of the cases. RESULTS: The patients age ranged from 28 to 62 years (mean = 43 years). The male-to-female ratio was 2:3. The clinical presentation included nasal obstruction, nasal discharge, nasal bleeding, facial pain, facial swelling, toothache and tear overflow. All of the 5 patients suffered from disease relapses; and 4 of them had recurrences for more than 5 times. One patient had lymph node metastasis and 3 patients died of the disease. Histologically, the tumor cells were arranged in interlacing fascicles and sometimes haphazard in fashion. They were spindly in shape, cytoplasm eosinophilic with mild nuclear atypia and a low mitotic activity. The intervening stroma was myxoid in appearance accompanied by lymphocyte and plasma cell infiltration, abundant blood vessels and focal collagenized areas. In 3 of the recurrent cases, the tumor cells displayed increased nuclear atypia and mitotic activity (average about 5 to 6 per 10 high-power fields), accompanied by patchy necrosis, less inflammatory cell infiltration and focal sarcomatous changes. Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin. SMA, MSA, calponin and fibronectin were variably expressed. Desmin was weakly positive in 1 case. The staining for h-caldesmon, ALK, S-100 and CK was negative. The Ki-67 proliferation index increased with tumor recurrences. Electron microscopy revealed abundant rough endoplasmic reticulum and dense body formation in the cytoplasm. There were an increased amount of collagen fibers in the stroma. CONCLUSIONS: IMT rarely occurs in nasal cavity and paranasal sinuses. The tumor is prone to local invasion and recurrences, with subsequent progression to frank malignancy and distant metastasis, resulting in high mortality and poor prognosis. Complete surgical resection remains the main modality of treatment.

Fibronexus in low-grade myofibrosarcoma: a case report.

Fibronexus (fibronexus junction) has been thought to be a characteristic ultrastructural feature of myofibroblasts, but it is controversial as to whether fibronexus is a characteristic of various myofibroblastic tumors. We report here a case of low-grade myofibrosarcoma with fibronexus arising in the right arm of an 80-year-old man. Histologically, the tumor was composed of relatively uniform and slender spindle cells arranged in fascicles. The nuclei with fusiform and tapered shapes were mildly hyperchromatic, but never exhibited pleomorphism. Mitotic figures were common, but no atypical mitosis was identified. At the tumor periphery, tumor cells had invaded into the surrounding skeletal muscle tissue. Tumor cells were positive diffusely for alpha-smooth muscle actin and less intensely for desmin, but were negative for h-caldesmon and S-100 protein. Ultrastructurally, tumor cells had well developed cytoplasmic organelles and varying amounts of peripheral or subplasmalemmal bundles of thin myofilaments with focal density. In addition, well formed, long fibronectin fibrils adjacent to the cell surface and fibronexus contacting intracellular myofilaments were easily identified. We believe that fibronexus is a useful ultrastructural feature for differentiating myofibrosarcoma from other myogenic sarcomas.

Divergent myoid, neuroendocrine, and perineural differentiation in a nasal tumor of a patient with Carney complex.

A 39-year-old woman with Carney complex presented with a stroke of undetermined etiology. Computed tomography showed bilateral thalamic infarctions and also an unsuspected multicompartmental cystic neoplasm that had eroded the anterior clivus and extended forward into the nasopharynx. Histologically, the mass appeared benign and was composed of spindle cells and multiple foci of striated muscle. Immunohistochemically, the spindle cells were strongly reactive for S-100 protein and to a lesser extent for CD57, collagen IV, neuron-specific enolase, smooth muscle actin, epithelial membrane antigen, and glut-1. The striated muscle cells were positive for desmin and myogenin. The MIB-1 labeling index was 0.5%. Ultrastructural examination was necessary to reveal the full extent of divergent differentiation. Ultrastructurally, the spindle cells showed divergent differentiation along several cell lines, including smooth muscle, neuroendocrine, hybrid smooth muscle-neuroendocrine, perineural-like cells, and striated muscle. The occurrence of this unique lesion in a patient with the Carney complex raises the possibility that it may be a rare component of the syndrome.

Angiomyofibroblastoma-like tumor (cellular angiofibroma) in the male inguinal region.

Angiomyofibroblastoma-like tumor is a rare mesenchymal tumor involving the male genital tract. We report a case of an angiomyofibroblastoma-like tumor that arose in the subcutaneous tissue of the left inguinal region in a 50-year-old man. Ultrasonography of the region demonstrated a well-circumscribed subcutaneous mass. Intralesional fat was revealed on magnetic resonance images. Although these imaging features are nonspecific, radiological findings enable considering the diagnosis of angiomyofibroblastoma-like tumor.

The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. part 2 - tumours and tumour-like lesions.

This paper describes the ultrastructure of the commoner myofibroblastic tumours and tumour-like lesions. The objective is to complement mainstream pathology texts, which have concentrated on the clinical and light microscopy features of these lesions and which have arguably but understandably somewhat neglected electron microscopy as an ancillary diagnostic tool and a technique for investigating tumour cell biology. Ultrastructural features are described of nodular fasciitis, the myofibromatoses (including Dupuytren's disease), inflammatory myofibroblastic tumour, post-operative spindle cell nodule, fibroma of tendon sheath, fibrous pseudotumour, benign fibrous histiocytoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, myofibrosarcoma (myofibroblastic sarcoma), malignant fibrous histiocytoma (pleomorphic myofibrosarcoma), epithelioid sarcoma and spindle-cell carcinoma. Fibrosarcoma and leiomyosarcoma are illustrated for comparison. The fibronexus is emphasised as an important marker for the most confident diagnosis of myofibrosarcoma. Some pathologists accept a light microscope definition, which includes alpha-smooth-muscle actin positivity, h-caldesmon negativity and, in some cases, desmin positivity. Caution in the interpretation of desmin staining in a possible myofibroblastic lesion is urged, since, in combination with an ultrastructurally identified lamina, it more probably suggests true smooth-muscle differentiation. Myofibroblastoma and angiomyofibroblastoma are examples of tumours argued on the basis of ultrastructural findings (sometimes in combination with desmin staining) to be primitively differentiated smooth-muscle cell rather than myofibroblastic proliferations.

The spectrum of pediatric fibroblastic and myofibroblastic tumors.

Fibroblastic and myofibroblastic tumors in neonates, infants, and children provide a diagnostic dilemma in surgical pathology due to their relative rarity and similarity in appearances. These tumors may be congenital or occur early during the first years of life or later during the first and second decades of life. The morphologic, immunocytochemical, ultrastructural, cytogenetic, and molecular features of the more "common" pediatric fibroblastic and myofibroblastic tumors are reviewed. In addition, the importance of a multimodal approach to tumor diagnosis is emphasized, with correlation with treatment and outcome differences among these unique fibroblastic and myofibroblastic tumors. The importance of providing an accurate diagnosis with pediatric fibroblastic and myofibroblastic tumors cannot be overstated, because treatment, prognosis, follow-up, and outcome are based on the initial assessment of these fascinating, but oftentimes, perplexing tumors.

Low-grade sarcomas with CD34-positive fibroblasts and low-grade myofibroblastic sarcomas.

A subset of low-grade fibrosarcomas is composed of CD34-positive spindle cells. These include dermatofibrosarcoma, its morphologic variants, and its associated fibrosarcoma, solitary fibrous tumor, hemangiopericytoma and their malignant counterparts, and some cases of myxoinflammatory fibroblastic sarcoma. Dermatofibrosarcoma and related lesions are characterized by a t(17;22)(q22;q13) rearrangement resulting in fusion of the genes COL1A (17q21-22) and PDGFB1 (22q13). Solitary fibrous tumor displays varying cellularity and fibrosis and a peripheral hemangiopericytomatous pattern; most tumors formerly called hemangiopericytoma are now subsumed into the category of solitary fibrous tumor, although a few strictly defined examples are recognized; however, these are probably not composed of pericytes. Myofibroblastic malignancies are best identified by electron microscopy, with which varying degrees of differentiation, including the presence of fibronexus junctions, can be identified. Low-grade sarcomas showing myofibroblastic differentiation include myofibrosarcomas and inflammatory myofibroblastic tumors. Myofibrosarcomas are spindle cell neoplasms that occur in children or adults in the head and neck, trunk, and extremities as infiltrative neoplasms and that display a fascicular or fasciitis-like pattern with focal nuclear atypia and variable expression of myoid antigens. These sarcomas are prone to recurrence and a small number metastasize. Inflammatory myofibroblastic tumor (synonymous with inflammatory fibrosarcoma) is a neoplasm arising predominantly in childhood, and frequently in intraabdominal locations. It has spindle cells in fascicular, fasciitis-like and sclerosing patterns, with heavy chronic inflammation including abundant plasma cells. Many IMT have clonal chromosomal abnormalities involving 2p22-24, and fusion of the ALK gene with tropomyosin 3 (TPM3-ALK) or tropomyosin 4 (TPM4-ALK) is found in a subset.

Electron microscopy in the study of myofibroblastic lesions.

Electron microscopy in the diagnosis and academic study of myofibroblastic lesions is discussed. Myofibroblasts from granulation tissue and tumor stroma are regarded as the nearest equivalent to a "normal" myofibroblast population with which to define myofibroblastic differentiation in tumoral and pseudotumoral lesions. Histological features include a plump-spindle-cell morphology, with an ill-defined cytoplasm paler and less fibrillar than in smooth-muscle cells, and matrix collagen. Myofibroblasts stain for alpha-smooth-muscle actin, fibronectin, and vimentin. Desmin is found in some lesional myofibroblasts. The main ultrastructural features are prominent rough endoplasmic reticulum, modestly developed myofilaments with focal densities ("stress fibers"), and fibronexus junctions. The latter are foci on the cell surface where intracellular myofilaments and extracellular fibronectin filaments converge. Myofibroblastic lesions vary in the extent to which they mirror this overall phenotype. Hypertrophic scar, Dupuytren's disease, nodular fasciitis, the fibromatoses, and inflammatory myofibroblastic tumors have the most developed myofibroblastic features. Keloid, postoperative spindle-cell nodule, and fibroma of tendon sheath are less well differentiated. Myofibroblastoma is among many lesions described as myofibroblastic which, however, appear to show a kind of smooth-muscle differentiation. Some spindle-cell malignancies express myofibroblastic features.

Intranodal myofibroblastoma: study of a case suggesting smooth-muscle differentiation.

A case of intranodal myofibroblastoma with amianthoid fibres was studied by histology, immunohistochemistry and electron microscopy, in a Canadian Caucasian male presenting with an inguinal mass which appeared following a sports injury. Tumour cells were spindled and formed haphazard interlacing fascicles with intervening areas of haemorrhage. They were positive for vimentin, alpha-smooth-muscle actin and HHF35. By electron microscopy, they displayed moderate numbers of rough endoplasmic reticulum cisternae, fine actin-sized filaments in cell processes, and discrete stretches of unambiguous lamina ('external' lamina), sometimes in association with short attachment plaques. The fibronectin fibrils and fibronexus junctions characteristic of myofibroblasts were not seen. The absence of fibronexus junctions and the presence of surface features typical of smooth-muscle cells (attachment plaques with overlying lamina) suggest that this tumour is not myofibroblastic but is exhibiting a degree of smooth-muscle differentiation. The findings confirm earlier observations suggesting that some intranodal myofibroblastomas are not myofibroblastic, but show a form of smooth-muscle differentiation.

Fine needle aspiration of breast myofibroblastoma. A case report.

BACKGROUND: The use of fine needle aspiration cytology (FNAC) for the diagnosis of breast diseases in men has received little attention. We report the cytologic and histologic findings of myofibroblastoma of the breast in a 52-year-old man. CASE: Smears disclosed irregular and cohesive sheets of cells, with ill-defined cytoplasm and oval nuclei containing single nucleoli. The nuclear membrane was frequently grooved, and occasional intranuclear cytoplasmic inclusions (pseudoinclusions) were also found. The background was clean and contained scarce collagenous stroma and fragments of myxoid material. To the best of our knowledge, there have been only seven previous reports of breast myofibroblastoma in which the cytologic features are well documented, and none of them mention the presence of pseudoinclusions. CONCLUSION: FNAC could suggest the diagnosis of this distinctly uncommon tumor if evaluated together with the clinical and radiologic findings.

Myofibroblastoma of the neck in a heifer.

A 1.5-year-old Holstein heifer had a subcutaneous tumor mass (20 cm diameter) on the ventral portion of the neck, and the tumor was diagnosed as a locally invasive myofibroblastoma. It consisted of moderately cellular fibrous tissue, and the interlobular septum of the thymus was invaded by tumor cells. The neoplastic cells were positive for alpha smooth muscle actin and vimentin, but not for desmin. Electron microscopy disclosed the presence of moderately developed rough endoplasmic reticulum and microfilaments with focal densities.

Myofibroblastic tumours: neoplasias with divergent behaviour. Ultrastructural and flow cytometric analysis.

Myofibroblasts are spindle cells having ultrastructural features in common with smooth muscle cells and fibroblasts. In the last few years, tumours have been described in which myofibroblasts represent not only a reactive mechanism but also a true neoplastic component. They constitute new nosologic entities which might be termed "myofibroblastic tumours". Tumours with benign and, rarely, malignant behaviour are reported to belong to this group of lesions. Recently, a third tumour type with borderline biological course, named "inflammatory myofibroblastic tumour" (IMT), has been identified, a condition that has been regarded as a benign and reactive disorder for a long time. Only in recent reports has been demonstrated that, in spite of an apparently benign morphological pattern, some cases of IMT have a malignant course. In this connection, DNA analysis by flow cytometry is a valuable diagnostic tool, because it allows identification of the ploidy status, a procedure that is often useful for predicting the nature and the biological behaviour of the lesion. In this study, 11 cases of myofibroblastic tumours were examined retrospectively by evaluating clinicopathological features and DNA ploidy status by flow cytometry. The diagnosis of myofibroblastic tumour was confirmed by performing histology, immunohistochemistry, and electron microscopy in all patients. In detail, these 11 cases were composed of 1 benign myofibroblastoma, 1 myofibrosarcoma and 9 IMTs. Among these myofibroblastic tumours, all those with local recurrence or distant metastases (one myofibrosarcoma and three IMT) showed an aneuploid cell population demonstrable by flow cytometric analysis, whereas the other cases with benign course (one benign myofibroblastoma and six IMT) exhibited an euploid DNA content. These data suggest the following: a) Besides the rare myofibroblastomas and myofibrosarcomas, IMTs represent a larger group of lesions with potentially different biological and clinical course. b) DNA flow cytometric analysis is a reliable tool that support histopathological examination in characterizing those cases of IMT that, though being malignant, mimic benign lesions. Consequently, it establishes the basis for a different therapeutic approach according to the euploid or aneuploid DNA content.

Myofibroblastoma of breast: evidence favoring smooth-muscle rather than myofibroblastic differentiation.

A histopathological study of two cases of the tumor known in the literature as myofibroblastoma of the breast is presented. The tumors occurred in Caucasian males aged 57 and 62 years. Histologically, these were moderately cellular, lobulated spindle-cell lesions, each with a reasonably well-delineated edge with surrounding fatty connective tissue. No breast ducts or lobules were present. Tumor cell nuclei were bland, with small nucleoli and some nuclear grooving. Nuclear atypia and mitoses were absent. Immunostaining revealed positivity for a-smooth-muscle actin, desmin, and CD34. Tumor cells contained rough endoplasmic reticulum, bundles of myofilaments with focal densities, intermediate filaments, attachment plaques alternating with plasmalemmal caveolae, and focal lamina. Ultrastructural findings pointed to true smooth-muscle differentiation, and the cell-surface in particular lacked surface features of myofibroblasts (fibronectin fibrils [microtendons] and fibronexus junctions). These and published data suggest that at least some of the lesions referred to in the literature as myofibroblastoma may not be myofibroblastic and may be better designated as myogenic stromal tumors or as variants of leiomyoma.

Myofibroblastoma of the ovary: report of a case.

We report an unusual case of an ovarian tumor arising in a 22-year-old female that showed histologic, immunohistochemical, and ultrastructural features of myofibroblastic differentiation. The mass was found incidentally and upon excision was 9.0 cm in its greatest dimension and almost entirely replaced the left ovary. The patient is alive without evidence of disease 21 months after excision. Histologically, the tumor was encapsulated and composed of cytologically bland spindled cells arranged into a variety of patterns, similar to those found in both solitary fibrous tumor and hemangiopericytoma. Immunohistochemically, the cells stained strongly for smooth muscle actin and muscle-specific actin, with only focal and weak staining for CD34. Stains for S-100 protein, desmin, and AE1/AE3 were negative. Ultrastructurally, the neoplastic cells showed clear-cut evidence of myofibroblastic differentiation. The differential diagnostic considerations, including solitary fibrous tumor and hemangiopericytoma, are discussed.

Benign spindle cell tumor of the breast with prominent adipocytic component.

We report a rare case of "benign spindle cell tumor of the breast with prominent adipocytic component" and present a review of the literature on the topic. The close morphologic resemblance with myofibroblastoma and spindle cell lipoma of the breast is emphasized and used as a starting point for diagnostic and histogenetic considerations. Although immunocytochemistry and electron microscopy showed features favoring a diagnosis of spindle cell lipoma, they were not conclusive. The tumor described here contributes to widen the spectrum of the benign spindle cell tumors of the breast variously named "benign spindle cell tumor," myofibroblastoma, spindle cell lipoma, and fibroma. It is important to distinguish this lesion from spindle cell metaplastic carcinoma and aggressive fibromatosis.