Characterization of the leiomyomatous variant of myofibroblastoma: a rare subset distinct from other smooth muscle tumors of the breast.

Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Myofibroblastoma belongs to a family of CD34-positive tumors with similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. A subset of these tumors demonstrates distinct smooth muscle differentiation. We aimed to characterize 4 cases of the leiomyomatous variant of myofibroblastoma arising in the breast by clinicopathological, immunohistochemical, and molecular means. All 4 examples arose in women aged 41 to 62 years (median, 46.5 years). Tumors ranged in size from 1.7 to 2.5 cm (median, 2.2 cm). Morphologically, all tumors were characterized by bundles of smooth muscle cells with elongated cigar-shaped nuclei and eosinophilic cytoplasm. All 4 tumors showed diffuse positive staining with desmin, caldesmon, smooth muscle actin, estrogen receptor, and Bcl-2. CD34 staining was diffusely positive in 2 cases, was weak and patchy in 1 case, and was negative in 1 case. Two (50%) of 4 tumors showed deletion of RB1 by fluorescence in situ hybridization. Loss of Rb staining was seen in 1 tumor with RB1 deletion by fluorescence in situ hybridization, whereas intact Rb staining was observed in 1 nondeleted case studied. In conclusion, this rare variant of myofibroblastoma is a distinct subgroup of tumors among an already uncommon category of (smooth muscle) breast tumors. Some reported examples of "parenchymal leiomyoma" may represent the leiomyomatous variant of myofibroblastoma.

Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis.

Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed leiomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation 'smooth muscle tumor of uncertain biologic potential' is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution ('dedifferentiation'). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBV-associated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing 'chaotic' karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.

Rare non-epithelial primary breast neoplasms: a ten-year experience at a Greek University Hospital.

PURPOSE: Non-epithelial breast neoplasms cover a large spectrum of histopathological entities. The demographics and clinical features are similar to epithelial breast lesions but the diagnosis, prognosis and management options are often very different. METHODS: During 2001-2010, 1362 patients were examined at the Pathology Department of the Aretaieion General Hospital for various breast lesions. All specimens were processed routinely and slides stained with hematoxylin-eosin were re-examined. The patient clinical records were examined for demographics, clinical presentation and therapeutic approach. RESULTS: In 23/1362 cases (1.68%) pathological examination showed non-epithelial lesions: in 12/1362 cases (0.8%) haemangiomas (11 women, one man), in 4 /1362 cases (0.3%) myofibroblastomas (MFB), in 2/1362 cases (0.1%) primary breast non-Hodgkin's lymphoma (NHL), in 3 /1362 cases (0.2%) granular cell tumor (GCT), and in 2/1362 cases (0.1%) angiosarcomas (one developed after radiotherapy for breast cancer). CONCLUSIONS: Non-epithelial primary breast tumors are rare (1.68%) and present significant difficulty in accurate preoperative diagnosis and in certain cases in pathological diagnosis as well, which is necessary for the selection of the appropriate treatment. Avoidance of inappropriate therapies requires a multidisciplinary management approach.

The immunohistochemical profile of oral inflammatory myofibroblastic tumors.

OBJECTIVE: The aim of this study was to demonstrate the immunohistochemical profile of oral inflammatory myofibroblastic tumors (IMTs) along with morphologic analysis. STUDY DESIGN: Three cases diagnosed as oral IMTs were selected to compile an immunohistochemical panel constituted by calponin, caldesmon, Bcl-2, desmin, fibronectin, CD68, Ki-67, S100, anaplastic lymphoma kinase (ALK), α-smooth muscle actin, cytokeratins AE1/AE3, muscle-specific actin, CD34, and vimentin. An oral squamous cell carcinoma with a focal area of desmoplastic stroma was used as control for the stained myofibroblastic cells. RESULTS: All oral IMTs were positive for calponin, revealing a strong and diffuse expression in the spindle-shaped cells. The lesions were also positive for vimentin (3/3), fibronectin (3/3), α-smooth muscle actin (3/3), and muscle-specific actin (1/3) and negative for h-caldesmon, Bcl-2, desmin, CD68, Ki-67, S100, ALK, cytokeratins AE1/AE3, and CD34. CONCLUSIONS: Within the results encountered, the present panel should be of great assistance in the diagnosis of oral IMTs.

[Indication of chemotherapy according to histological type of musculoskeletal sarcomas].

In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed to prevent distant metastases. As the efficacy of chemotherapy varies according to the histological type of sarcoma, its indication is determined according to the histological type and the stage. Prognoses are poor in patients with osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses are improved with adjuvant chemotherapy, so it is absolutely necessary. Drugs commonly used for osteosarcoma include adriamycin, cisplatin, methotrexate, vincristine, and ifosfamide. For Ewing's sarcoma and rhabdomyosarcoma, vincristine, actinomycin-D, cyclophosphamide, etoposide, and ifosfamide are commonly used. On the other hand, the efficacy of chemotherapy is unclear in most of the non-round cell sarcomas, e. g., malignant fibrous histiocytoma, pleomorphic liposarcoma, and leiomyosarcoma, so adjuvant chemotherapy is relatively indicated and often performed preoperatively. The efficacy is evaluated by reduction of the tumor volume as a surrogate marker. Postoperative chemotherapy is performed when the preoperative chemotherapy is effective. Nowadays, several kinds of antitumor agents are usually used for non-round cell sarcomas, and many authors have reported various kinds of regimens and their clinical results. Among them, the key drugs are adriamycin and ifosfamide. Recently, taxanes and gemcitabine are sometimes used. For chemoresistant sarcomas, e. g., chondrosarcoma, chordoma, alveolar soft part sarcoma, chemotherapy is rarely indicated, even if the tumor is histologically high grade and large. Low-grade musculoskeletal sarcomas, e. g., low-grade chondrosarcoma, central low-grade osteosarcoma, parosteal osteosarcoma, well-differentiated liposarcoma, and dermatofibrosarcoma protuberans, are well cured only by surgical excision, and adjuvant chemotherapy is therefore not indicated. Superficially-located, small-size non-round cell sarcomas, even though histologically high grade, are well healed only by surgical excision, and adjuvant chemotherapy is rarely indicated.

Perivascular myoid tumors of the oral region: a clinicopathologic re-evaluation of 35 cases.

BACKGROUND: Myopericytoma (MPC) is a generic denomination to describe tumors showing differentiation toward perivascular myoid cells /myopericytes. It has been suggested that MPC forms a morphologic continuum with glomus tumor (GT), solitary myofibroma (SMF), and angioleiomyoma (ALM). This proposed relationship has not yet been assessed in the oral region. METHODS: We reviewed our 28-year experience with 35 oral tumors, originally diagnosed as ALM (n = 28), SMF (n = 4), GT (n = 2), and MPC (n = 1) to analyze their overlapping microscopic features, with the assistance of immunohistochemistry. RESULTS: Myopericytoma showed a wide range of growth patterns; concentric perivascular whorls, hemangiopericytomatous areas, glomangiopericytoma (GPC)-type vessels and leiomyomatous foci. Intravascular growth was also seen. Among 28 cases studied, three ALM were reclassified as MPC (n = 2) and SMF (n = 1), based on the present diagnostic criteria. Additional MPC-type components, at varying degrees, were similarly found in four ALM and three SMF, at least focally. One GT featured intravascular whorls of spindle cells. These four interrelated groups of tumors had in common GPC-type vasculature and intraluminal cellular proliferation was nearly ubiquitously present. Diffuse immunoreactivity for alpha-smooth muscle actin and less staining intensity of muscle-specific actin were observed in all tumors. Only ALM displayed desmin positivity of variable extent. Neither case tested expressed CD34. CONCLUSIONS: Our data matches with the recent results in extraoral sites that MPC, GT, SMF, and ALM exhibit histologic and immunohistochemical overlap with each other. A common perivascular myoid differentiation between these tumor types is further reinforced by the present oral series.

Evaluation of biological potential of smooth muscle tumours.

Smooth muscle tumours (SMTs) have been traditionally divided into benign leiomyomas (LM) and malignant leiomyosarcomas (LMS) based on cytological atypia, mitotic activity and other criteria. In most instances, this dichotomous approach works, but in some instances the biological potential cannot be determined with certainty. This is often because some, but not all criteria for malignancy have been met or because the tumours are occurring in unusual settings for which there are sparse substantive data. Tumours falling into the latter categories are often designated as 'smooth muscle tumours of uncertain malignant potential'. For most non-hormonally influenced SMTs, the presence of significant atypia plus mitotic activity equates with a diagnosis of LMS. However, not all tumours classified as LMSs have a similar prognosis, as a number of other factors, including tumour size, depth, grade and resectability, affect outcome. For example, cutaneous SMTs, regardless of mitotic activity and atypia, have potential largely limited to local recurrence, whereas subcutaneous and deep LMSs have a definite metastatic potential. Angioleiomyoma is the most common SMT of peripheral soft tissues, but deep peripheral LMs are distinctly rare and should be approached with caution. Hormonally influenced oestrogen- and progesterone receptor-positive uterine and extrauterine SMTs in women have unique criteria, including the allowance of higher mitotic activity for the benign LM designation. SMTs of female genital tract can be assessed with criteria similar to uterine tumours. Because of the rarity of these tumours, experience is more limited, and more caution is needed to assess the potential of tumours with mitotic activity and atypia. This review summarizes the current knowledge, guidelines, prognostic data and controversies for the classification of SMTs of soft tissue and most visceral sites.

An approach to the classification of spindle cell proliferations in the urinary bladder.

Spindle cell proliferations of the urinary bladder are uncommon but may cause significant diagnostic difficulty resulting from the degree of morphologic overlap between clinically benign and malignant lesions. These difficulties may be amplified in small biopsies because some of the more specific diagnostic features may not be present for evaluation. In addition, the number of different diagnostic terms applied to the same entity has added confusion to this diagnostic area. This review discusses the nomenclature, morphologic criteria, and immunohistochemical features used to classify spindle cell proliferations occurring in the urinary bladder, including those with myofibroblastic, smooth muscle, skeletal muscle, epithelial (sarcomatoid urothelial carcinoma), fibroblastic, and neural differentiation. A separate discussion of 5 challenging differential diagnostic scenarios is also presented.

Angiomyxoid tumor with an intermediate feature between cellular angiofibroma and angiomyofibroblastoma in the male inguinal region.

Angiomyofibroblastoma (AMFB) and cellular angiofibroma (CA) are angiomyxoid tumors which infrequently arise in the female vulvovagina and each has been proposed to be a distinct clinicopathological entity. The former in male genitalia is exceedingly rare and has been described as its male analog or under the name of male AMFB-like tumor, while the latter in men has not been reported. We describe an angiomyxoid tumor which appeared in the inguinal region of 72-year-old man. The present case had a histopathological characteristic and immunophenotype intermediate between AMFB and CA. Male genital angiomyxoid tumors share many immunopathological features with their female counterparts, suggesting that they are male homologs rather than analogs. Immature mesenchymal cells with a potential of the multilineage differentiation might be promoted toward neoplastic myoblasts, fibroblasts and adipocytes, resulting in genital angiomyxoid tumors showing a broad spectrum in the immunopathological phenotype.

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.

Oral spindle cell neoplasms: a review of 307 cases.

The infrequent exposure of pathologists to soft tissue spindle cell neoplasms coupled with overlapping histologic patterns can often make diagnosis challenging. We reviewed all nonodontogenic spindle cell neoplasms seen between 1982 and 2002 (86,162 total accessions). Diagnoses were reclassified according to current standards supplemented with immunohistochemistry. Of the 307 neoplasms reviewed (0.36% of total accessions), neural tumors were the most common benign entities, accounting for 21% of total cases. Kaposi's sarcoma was the most common malignancy, accounting for 67% of all cases. Diagnoses were revised for 57 cases. Schwannoma and neurofibroma were most commonly revised to palisaded encapsulated neuroma. There were 8 myofibromas and 1 inflammatory myofibroblastic tumor. There were no oral leiomyomas; that is, all 4 originally reported cases were reclassified as myofibroma, palisaded encapsulated neuroma, and solitary fibrous tumor. With the exception of Kaposi's sarcoma, oral soft tissue sarcomas were rare; most benign lesions were neural in origin. The relatively high prevalence of some tumors, such as myofibroma, likely reflects the use of immunohistochemistry in the diagnosis of spindle cell tumors.

Risk assignment in pediatric soft-tissue sarcomas: an evolving molecular classification.

Pediatric soft-tissue sarcomas are increasingly being defined by both histologic appearance and underlying chromosomal abnormalities to determine their biologic behavior. Most sarcomas of this type have specific chromosomal translocations that create unique fusion genes. Expression of such fusion genes may have diagnostic, prognostic, and surveillance implications for the patient. This review analyzes the fusion gene expressions seen with seven of the major types of pediatric soft-tissue tumors and their impact on biologic behavior. In nearly 50% of the malignancies discussed, the diagnostic, prognostic, and surveillance implications of their specific fusion gene expressions are already defined or becoming established (alveolar rhabdomyosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, and synovial sarcoma). In the remainder of the tumors, these questions are rapidly being addressed. To facilitate future fusion gene studies, pediatric surgeons, pathologists, and oncologists need to work as a coordinated team to ensure proper tumor procurement. Large clinical cooperative trials involving biologic studies of pediatric soft-tissue sarcomas could facilitate advancement of knowledge in this area of pediatric oncology.

Piloleiomiomas cutáneos múltiples, nofamiliares / Multiple, non-familial cutaneous piloleomyomata

Los piloleiomiomas cutáneos son tumores benignos de las células musculares lisas que existen en el músculo arrector del pelo. Estos tumores son poco frecuentes y suelen consistir en lesiones aisladas y dolorosas, localizadas en la parte proximal de las extremidades, aunque también se han comunicado formas múltiples familiares, con un patrón hereditario de tipo autosómico dominante. Se describe una presentación clínica inhabitual de piloleiomiomas cutáneos múltiples, no familiares, agrupados en la espalda y formando una placa liquenificada por el rascamiento debido al prurito que inducían las lesiones (AU)

Recent progress in the classification of soft tissue tumors: role of genetics and clinical implications.

Soft tissue tumors comprise a vast and heterogeneous group of neoplasms. Because different tumors often have different biological behaviors and respond differently to various therapeutic modalities, precise classification is paramount. The majority of soft tissue tumors were first delineated on the basis of morphologic and clinical findings, which in many cases were adequate to accurately separate different tumors into homogeneous groups; however, it has increasingly been appreciated that many entities are actually heterogeneous groups of tumors that have similar histologic and pathologic characteristics but differ in their clinical behavior and underlying pathogenesis. Within the past several years, great strides have been made in the purification of different entities. This accomplishment has largely been because of advances in our understanding of the molecular genetics that underlie the pathogenesis of many sarcomas and the development of new and specific tumor markers. This review highlights some important recent work in two selected soft tissue tumors-gastrointestinal stromal tumor and inflammatory myofibroblastic tumor. These examples illustrate the type of progress that is being made in the classification of soft tissue tumors.

Myofibroblastic tumours: an update.

The concept of the myofibroblast is relatively new, since this cell type was defined less than 30 years ago, and there is as yet no firm consensus as to how a myofibroblast should be defined either morphologically or phenotypically. Because its attributes place it midway between a fibroblast and a smooth muscle cell and because it appears capable of functional and phenotypic modulation, some authorities argue that there is no such thing as a truly myofibroblastic tumour. However, since most diagnostic tumour pathology is based on phenotypic features of the excised lesion, it is an unavoidable fact that a wide range of soft tissue tumours show convincing myofibroblastic features. Lesions in this category fall into four main groups--the family of reactive fasciitis-like lesions, a group of benign lesions most of which have been fairly recently recognized (e.g., mammary myofibrolastoma, intranodal myofibroblastoma, angiomyo-fibroblastoma and dermatomyofibroma), the locally aggressive fibromatoses (either superficial or deep) which share features of fibroblasts and myofibroblasts in varying degree and, finally, sarcomas showing myofibroblastic differentiation. These latter include low grade lesions such as so-called infantile fibrosarcoma, inflammatory myofibroblastic tumour and a distinctive form of low grade myofibroblastic sarcoma, as well as some of the high grade lesions formerly known as MFH. Based on the advances made in the past 20 years, it makes no sense to deny the existence of myofibroblastic tumours (especially in an era when histogenetic concepts have crumbled)--instead we need to work towards a reproducible and agreed definition of the myofibroblast.

Subclassification of gastrointestinal stromal tumors based on evaluation by electron microscopy and immunohistochemistry.

Fifty-six gastrointestinal stromal tumors (GIST) were subclassified by ultrastructural examination and by immunophenotypic analysis using a panel of 13 antibodies. Eighty percent of the tumors originated in the stomach and small intestines. The neoplasms were classified as follows: 42.9% smooth muscle tumors (4 leiomyomas, 9 spindle cell and 8 epithelioid leiomyosarcomas, and 3 mixed spindle cell and epithelioid leiomyosarcomas); 37.5% gastrointestinal autonomic nerve tumors (GANT), 47.6% of which arose in the small intestines; 8.9% mixed leiomyosarcoma/neurogenic tumors; and 10.7% undifferentiated GIST, not otherwise specified. The muscle common actin antibody HHF-35, variably reactive with tumor cells composing 23 of 24 smooth muscle tumors, was found to be the most sensitive marker of leiomyocyte differentiation. One immunophenotypically questionable spindle cell leiomyosarcoma was diagnosed by electron microscopy. Since neuron specific enolase positive cells were found in 1/3 of the leiomyosarcoma cases, the ultrastructural demonstration of synapse-like structures and neurosecretory granules was required for diagnosing GANTs. The immunophenotype of the ultrastructurally undifferentiated GIST was vimentin and CD34+. Variable numbers of ultrastructurally undifferentiated cells also we found in all of the tumors except 2 leiomyomas. CD34 was also expressed in smooth muscle (54%) and GAN (62%) tumors. Despite their similar light microscopic appearance, GIST are phenotypically heterogeneous, requiring both ultrastructural and immunohistochemical studies for accurate characterization.

Inflammatory leiomyosarcoma: a morphological subgroup within the heterogeneous family of so-called inflammatory malignant fibrous histiocytoma.

Twelve cases of inflammatory leiomyosarcoma are presented. These tumours arose in the deep soft tissues of the trunk and proximal limbs. The age of the patients ranged from 13-53 years (median 36 years); there was an approximately equal sex ratio. Follow-up data was available for nine patients (mean duration 3.3 years); local recurrence occurred in three and lung metastases in one. Lesions were spindle cell neoplasms with fascicular areas which occupied between 5% and 80% of the tumour. Areas with a distinct storiform pattern were also seen in 10 cases. A prominent inflammatory cell component was evident in all tumours, often masking the neoplastic spindle cells. Histiocytes were identified in all cases, with aggregates of xanthoma cells seen in eight tumours. In 10 cases there was also a dense lymphoid infiltrate and in two a marked polymorphonuclear leukocyte infiltrate was evident. Immunohistochemistry showed in all tumours that the spindle cells stained positively for myogenic markers (8 of 12 positive for desmin, 10 of 12 for alpha smooth muscle actin and 11 of 12 for HHF-35). CD68 was expressed by the histiocytic infiltrates. Many of these tumours were diagnosed initially as inflammatory malignant fibrous histiocytoma. We provide evidence that at least one subset of neoplasms, which would have been formerly classified under this rubric, in fact show smooth muscle differentiation. Further studies are required to investigate the possibility that other tumour types or lines of differentiation may be present within the category of so-called inflammatory malignant fibrous histiocytoma.

Diagnostic imaging of muscular tumors.

Eight patients with muscular tumors--all malignant--were reviewed. Seven patients were examined by magnetic resonance imaging. Some of them also underwent conventional radiology and computed tomography. One patient was examined by computed tomography only. An overview and short description of the muscular tumors are given. The findings with the different imaging techniques are presented, followed by a discussion of the role of the imaging techniques. The final conclusion is that MRI is the modality of choice for detection, staging, and follow-up of muscular tumors, although the signal intensity features are not always specific.