Intratumoural lymphatics in benign and malignant soft tissue tumours

Soft tissue sarcomas do not generally metastasise via lymphatics, and the presence or absence of lymphatic vessels within sarcomas and benign soft tissue tumours is not known. In this study, we determined whether lymphatic vessels were present in a wide range of benign and malignant soft tissue lesions by examining intratumoural expression of the lymphatic endothelial cell markers, Lyve-1 and podoplanin. Intratumoural Lyve-1+/podoplanin+ lymphatics were not identified in sarcomas apart from all cases of epithelioid sarcoma (a tumour which is known to metastasise to lymph nodes) and a few cases of leiomyosarcoma, rhabdomyosarcoma and synovial sarcoma. Intratumoural lymphatics were also absent in most benign soft tissue tumours. Reparative and inflammatory soft tissue lesions contained lymphatics, as did all (pseudosarcomatous) proliferative myofibroblastic lesions including nodular, proliferative and ischaemic fasciitis, elastofibroma, nuchal fibroma and deep fibromatosis. Our results show that most soft tissue sarcomas do not contain intratumoural lymphatics, a finding which is consistent with the infrequent finding of sarcoma metastasis to lymph nodes. In contrast to fibrosarcoma and a number of other malignant spindle cell tumours, proliferative fibroblastic/myofibroblastic lesions of soft tissue contain intralesional lymphatic vessels.     

Myofibroblasts in fibromatoses. An electron microscopic study

Fifteen cases of fibromatoses were analyzed by electron microscopy, the objective being to compare the incidence and frequency of myofibroblasts in each category. Myofibroblasts were identified in all 15 cases and a considerably large number of these cells appeared in palmar fibromatosis, plantar fibromatosis, and nodular fasciitis. In keloid and cicatricial fibromatosis, however, only a small number of these cells were evident. In seven cases of extra-abdominal desmoid fibromatosis, the frequency of myofibroblasts in the component cells ranged from 10% to 64%, with a mean of 30%. The frequency was high in hypercellular lesions and low in hypocellular lesions, assuming that it would be roughly in parallel to the cellularity of the lesion in extra-abdominal desmoid fibromatosis and in other fibromatoses as well. There appeared to be no particular correlation between the number of myofibroblasts and recurrence of the lesion.     

MYOFIBROBLASTS IN FIBROMATOSES An Electron Microscopic Study

Fifteen cases of fibromatoses were analyzed by electron microscopy, the objective being to compare the incidence and frequency of myofibroblasts in each category. Myofibroblasts were identified in all 15 cases and a considerably large number of these cells appeared in palmar fibromatosis, plantar fibromatosis, and nodular fasciitis. In keloid and cicatricial fibromatosis, however, only a small number of these cells were evident. In seven cases of extra-abdominal desmoid fibromatosis, the frequency of myofibroblasts in the component cells ranged from 10% to 64%, with a mean of 30%. The frequency was high in hypercellular lesions and low in hypocellular lesions, assuming that it would be roughly in parallel to the cellularity of the lesion in extra-abdominal desmoid fibromatosis and in other fibromatoses as well. There appeared to be no particular correlation between the number of myofibroblasts and recurrence of the lesion. ACTA PATHOL. JPN. 35 : 533–547, 1985.     

Myofibrosarcoma

Myofibrosarcomas are malignant tumours of myofibroblasts, which have been recognised for many years, but have become clearly defined only recently. They are low- or high-grade sarcomas that arise in soft tissue or bone in adults or children. Low-grade myofibrosarcomas are infiltrative tumours, usually in deep soft tissue, with a predilection for the head and neck region, which display a range of microscopic appearances from fasciitis-like to fibrosarcoma-like; all cases at least focally display nuclear pleomorphism. They express smooth-muscle actin and calponin, and some express desmin, but most lack h-caldesmon. Low-grade myofibrosarcomas can recur but rarely metastasise. Their differential diagnosis is from benign myofibroblastic proliferations, such as fasciitis and fibromatosis, as well as from fibrosarcoma and leiomyosarcoma. Pleomorphic myofibrosarcomas are high-grade pleomorphic sarcomas (malignant fibrous histiocytoma), which show ultrastructural evidence of myofibroblastic differentiation. They closely resemble malignant fibrous histiocytoma clinically and morphologically, but are more frequently actin positive. This article describes the low- and high-grade variants of myofibrosarcoma and other malignant tumours with myofibroblastic differentiation.     

Fine-needle aspiration cytology and immunocytochemistry of soft-tissue tumors and osteo/chondrosarcomas of the head and neck

The purpose of the study was to present the clinical and cytological findings of 28 cases of malignant or borderline mesenchymal tumors of the head and neck, of which 22 originated from soft tissue and 6 were found in bone or cartilage. The basic procedures employed involved a cytologic review and subclassification of fine-needle aspiration (FNA) smears from the tumors, which were diagnosed as: pleomorphic sarcomas (5 poorly differentiated, 1 angiosarcoma, and 1 epithelioid sarcoma), spindle-cell sarcomas (2 leiomyosarcomas, 2 malignant mesenchymal tumors, and 1 malignant schwannoma), myxoid sarcomas (2 liposarcomas and 1 high-grade tumor), round-cell tumors (1 malignant histiocytic tumor and 1 chloroma), osteosarcomas (3), chondrosarcomas (3), and borderline tumors (2 pleomorphic lipoma, 1 myxolipoma, 1 cranial fasciitis, and 1 fibromatosis). Histological correlation and problems in subtyping on both cytologic and histological material are discussed. It is concluded that FNA cytology can be used with high accuracy to diagnose musculoskeletal tumors in rare sites such as the head and neck.     

Intracellular collagen and fibronexus in fibromatosis and other fibroblastic tumors

Myofibroblasts are mesenchymal cells with combined function and structure for contraction and collagen synthesis. They are found in reparative responses, nodular fasciitis, fibromatosis, and myofibroblastic sarcoma. Ultrastructurally, myofibroblasts are characterized by a specialized cell surface structure called the fibronexus (FNX). In addition, intracellular collagen fibers (ICF) have been described in nodular fasciitis and fibromatosis, but their origin and nature are still controversial. The aim of the present work was, first, to assess the frequency of FNX and ICF in proliferative myofibroblastic conditions compared to diverse mesenchymal tumors with spindle-shaped cells, and, second, to determine what kind of organelles contain ICF and if they are related to phagocytosis or cell synthesis. Forty-two cases of aggressive fibromatosis and 11 of nodular fasciitis (group A) were compared to 82 spindle-cell mesenchymal tumors of diverse nature (group B) by electron microscopy study. The presence and frequency of FNX and ICF was compared in both groups, and the organelles containing ICF were recorded. FNX and ICF were constantly found in group A (69.8 and 84.9%, respectively), and rarely in group B (0 and 5.12%, respectively). Most frequently ICF were contained in tunnels and phagolysosomes, but also were found in Golgi vesicles and cisternae of rough endoplasmic reticulum. In the majority of cases (75%), ICF were similar to collagen fibers of the extracellular space, but in some cases (22.5%), they were in dissimilar stages of fibrogenesis. Fibromatosis and nodular fasciitis are characterized by proliferation of myofibroblasts and constantly show FNX and ICF. These structures are rarely found in other mesenchymal tumors. The ICF are found in organelles of digestion and also in others related to synthesis and transport.     

Benign and malignant spindle cell lesions of the breast

Spindle cell lesions of the breast constitute a wide spectrum of benign and malignant proliferations. Myofibroblasts, normal cellular constituents of the mammary intra- and interlobular stroma, compose many of these lesions, which include reactive proliferations and benign or locally aggressive neoplasms. Because of its morphology, low-grade metaplastic spindle cell carcinoma, "fibromatosis-like" is also considered together with spindle cell lesions of the breast. Although certain of the lesions do not occur commonly, they represent diagnostic challenges. This review outlines the morphology of certain spindle cell lesions of the breast including pseudoangiomatous stromal hyperplasia, reactive spindle cell nodule, nodular fasciitis, myofibroblastoma, primary mammary fibromatosis, and low-grade metaplastic spindle cell carcinoma, "fibromatosis-like." The differential diagnosis and diagnostic work-up of these lesions is discussed, and their clinical treatment and prognosis briefly summarized.     

Myofibroblastic malignancies

Malignant tumors composed of myofibroblasts are increasingly being recognized, but their existence remains controversial. Currently accepted examples within this category represent spindle cell or pleomorphic neoplasms of the soft tissues with a spectrum of histological grades. Low- and intermediate-grade myofibrosarcomas are fascicular spindle cell neoplasms resembling fibrosarcoma or leiomyosarcoma. They infiltrate deep soft tissue with disproportionate involvement of head and neck sites and can recur locally but infrequently metastasize. They variably express myoid immunohistochemical markers, and their differential diagnosis includes benign myofibroblastic proliferations such as fasciitis and fibromatosis as well as other types of spindle cell sarcoma. High-grade (pleomorphic) myofibrosarcomas are an ultrastructurally defined subset of malignant fibrous histiocytoma, which they resemble in morphology and behavior. Inflammatory myofibroblastic tumor and infantile fibrosarcoma are neoplasms that have myofibroblastic features and have been included in this category, but they have distinctive genetic findings. This article reviews the concept of myofibrosarcoma and describes its variants.     

Squamous cell carcinoma of the lung with highly proliferating fibromatosis-like stroma: a rare phenomenon

Few cases of carcinoma with exuberant stromal proliferation have been documented, apart from scirrhous carcinoma. To the best of our knowledge, previous cases of carcinoma exhibiting exuberant stromal proliferation have exclusively been reported in the thyroid gland, specifically as papillary carcinoma. The exuberant stromal proliferation has been recognized to be similar to either fibromatosis or nodular fasciitis. Herein, we report a case of a 74-year-old Japanese man whose tumor in the upper lobe of his right lung displayed highly proliferating stroma with dispersed, poorly differentiated squamous cell carcinoma nests. The stromal spindle cells (fibroblasts/myofibroblasts) had similar molecular profiles to those typically observed in fibromatosis rather than nodular fasciitis, resulting in the designation of “fibromatosis-like” stroma. The presence of carcinoma cells, along with stromal cells, expressing TGF-β in this case likely fostered continuous stromal proliferation, presumably in conjunction with the unique microenvironment in which the carcinoma cells were present.     

Sklerosierendes epitheloides Fibrosarkom

The sclerosing epithelioid fibrosarcoma (SEF), defined as an entity by Meis-Kindblom et al. in 1995 [15] is now considered to be a variant of fibrosing fibrosarcomas. It is a rare tumor with an intermediate malignant potential leading to local recurrences in one third and to metastases in about 40% of the cases. We report six cases of this entity. At the time of diagnosis two patients of our series already showed metastases in the lungs. The tumors were located in the deep soft tissue and measured between 2.5 and 17 cm. The histology is characterized by small epithelioid cells that are arranged individually or in cords and nests and set typically in a hyaline sclerotic matrix. By immunohistochemistry, all cases were vimentin positive, however EMA positive cells are also possible. The differential diagnosis includes metastases of carcinoma, benign and malignant soft tissue tumors. The distinction of SEF from fibromatosis, fibrous histiocytomas, ossifying fibromyxoid tumors, clear cell sarcomas, epithelioid sarcomas, synovial sarcomas and extraskeletal osteosarcomas is discussed.     

Metaplastic spindle-cell (fibromatosis-like) carcinoma of the breast--report of 4 cases

The authors report about clinico-morphological features in four cases of spindle-cell metaplastic carcinoma of the breast, closely mimicking benign soft tissue fibromatosis or nodular fasciitis. All patients were females aged 54-72 years with a palpable nodule within the breast, 20-35 mm in size. Histologically, the tumor infiltrated surrounding tissue; it consisted of spindle cells with relatively bland morphology, arranged in a fascicular, storiform or random fashion. Mitotic activity was low, focally the tumors revealed regressive changes (hyalinization, myxoid degeneration). Cytokeratin expression was proven in all four cases. In two patients the tumor metastasized and the patients died of it; this fact confirms recently published data that despite its deceptively benign appearance, fibromatosis--like carcinoma of the breast is undoubtedly a malignant process with potentially aggressive behaviour. Differential diagnosis of this unusual variant of metaplastic breast carcinoma is discussed together with related therapeutic issues.     

Pseudosarcomatous lesions of the soft tissues reported as sarcoma during a 6-year period (1958-1963)

Pseudosarcomatous lesion of the soft tissues is a term used in the present study for various soft tissue lesions and tumours easily clinically or histologically, or both, misinterpreted as sarcoma. Eighty-one cases, that is to say 10 per cent of all tumours classified and reported to the Swedish Cancer Registry as malignant soft tissue tumours during the 6-year period studied (1958-1963), were reclassified as pseudosarcomatous lesions of the soft tissues. Forty-seven cases were classified as pseudoarcomatous proliferative lesions of the soft tissue with or without bone formation; 38 cases of nodular fasciitis, 1 of proliferative fasciitis and 8 of proliferative myositis. In 3 of these cases there were mixed forms of proliferative fasciitis and proliferative myositis with areas compatible with the diagnosis of nodular fasciitis evident in all cases. Twenty-two cases of atypical fibroxanthomas of the skin were next in frequency, followed by 7 ancient neurilemmomas, 2 spindle cell lipomas, 1 pseudomalignant osseous tumour of the soft tissues, 1 pigmented villonodular synovitis and 1 juvenile xanthogranuloma. An attempt is made to explain the reasons for these erroneous diagnoses of sarcoma and it is stressed that for these lesions the conventional histological criteria for malignancy are not valid. The awareness and knowledge of the existence of these particular entities are therefore considered mandatory for an accurate diagnosis.     

Fibroma of tendon sheath.

A series of nine cases of fibroma of tendon sheath is described including details of the ultrastructural features of two cases. The series was composed of lesions from six males and three females with a mean age of 38 yr. The most common site of involvement was the hand (including fingers) and the mean greater diameter was 19 mm. Typically the tumours were lobulated and microscopically there was a collagenous stroma with spindle and stellate cells in a moderate degree of cellularity. One recurrence was noted in the series. The lesion was distinguished from circumscribed fibromatosis, nodular fasciitis, neurofibroma, leiomyoma, scar tissue, giant cell tumour of tendon sheath (localised nodular tenosynovitis) and fibrous histiocytoma. Ultrastructural studies revealed that the large majority of cells present in the two cases studied were myofibroblasts and fibroma of tendon sheath is therefore the third instance of a benign tumour containing these cells (the other two being dermatofibroma and giant cell fibroma of the oral mucosa).     

Fibrous Lesions of the Breast: A Review

Fibrous lesions of the breast are challenging for a number of reasons. They occur infrequently and there is significant clinical, radiologic, and histologic overlap between reactive and neoplastic lesions, as well as with some nonfibrous lesions. Pure fibrous lesions of the breast encompass reactive conditions, such as scars and nodular fasciitis, and neoplastic entities, such as the distinct benign mammary myofibroblastoma, locally aggressive fibromatosis, and rare true sarcomas. In this review, we focus on nodular fasciitis, mammary myofibroblastoma, and primary mammary fibromatosis. We also briefly discuss spindle cell metaplastic carcinoma because it represents the most important differential diagnosis through its ability to closely simulate nodular fasciitis and fibromatosis. Caution should be exercised in the interpretation of fibrous lesions of the breast, especially if the tissue sample is limited. Int J Surg Pathol 8(2):99-108, 2000     

Cytological findings in nodular fasciitis

Nodular fasciitis, proliferative fasciitis, and proliferative myositis are tumorous proliferative soft tissue changes which on histological examination are quite often erroneously diagnosed as malignant neoplasms. Reported are cytological and histological findings recorded from nodular fasciitis in a man aged 34 years. The cytomorphology of nodular fasciitis is sufficiently characteristic, so that the lesion can be differentiated with certainty from malignant processes, since the cells have no features of malignancy, and the admixture of granulocytes and histiocytes in smears suggests a proliferative inflammatory process.     

Aggressive fibromatosis of the leg and sacrococcygeal region: a report of two cases

Aggressive fibromatosis is a rare soft tissue tumor that composes of myofibroblasts that arise from musculoaponeurotic structures. It usually affects the abdominal wall but may be also found in other less common sites including the head and neck, submucosa of the oral cavity, spinal, haunch and limbs, especially, the limbs and sacrococcygeal region are rare locations. We described two cases of aggressive fibromatosis. One was 3-year-old girl with aggressive fibromatosis arising from the right leg region. The other was 20-year-old female arising from in the sacrococcygeal region. They were resected with satisfied results. Pathological examination showed that they were composed of fibroblasts, fibrocytes and bundles of collagen fiber. The aggressive fibromatosis, although rare, should be differentiated from some other soft tissue tumors with similar histological features and different localizations of intra-abdominal, abdominal wall and extra-abdominal.     

Nodular fasciitis of the hand: a potential diagnostic pitfall in fine-needle aspiration cytopathology

Fine-needle aspiration biopsy (FNAB) is applied very uncommonly to soft tissue masses and even more infrequently to lesions of the hand. Nodular fasciitis, an uncommon pseudosarcomatous lesion of soft tissue, rarely occurs in the hand and, because of this, is not often considered in the differential diagnosis of hand masses. We report 3 cases (2 men and 1 woman; mean age, 44.3 years) of soft tissue masses of the hand, which, after clinical and radiologic evaluation, were strongly suspected by an experienced orthopedic oncologist as harboring a soft tissue sarcoma. Each patient underwent FNAB, which showed markedly hypercellular smears with overlapping, relatively isomorphic spindle cells that were mistaken cytologically as possible sarcoma in 2 cases; 1 case was considered probable nodular fasciitis. All lesions eventually were diagnosed as nodular fasciitis after thorough histologic and immunohistologic evaluation. Nodular fasciitis remains a difficult diagnosis by FNAB, particularly when it occurs in locations such as the hand.     

Do biomaterials cause implant-associated mesenchymal tumors of the breast? Analysis of 8 new cases and review of the literature

Implant-associated mesenchymal tumors (IAMT) of the breast are rare, and most are fibromatoses. There has been no systematic analysis of IAMT to determine their full histologic spectrum, whether there is an association with implant type or rupture, and if evidence supports a causal or fortuitous relationship between tumor and implant. We, therefore, analyzed all mesenchymal tumors associated with breast implants from our soft tissue consultation database spanning a period from 1989 to 2005. Information regarding location, type, and integrity of implant and its temporal relationship to tumor was recorded. Eight IAMT were identified exclusively in female patients (ages 28-64 years; median, 38 years), all of whom presented with a palpable mass. Tumors developed after placement of either a silicone (n = 7) or saline (n = 1) implant (median, 2 years; range, 1.8-10 years), which was usually inserted for cosmetic purposes (n = 7). All tumors arose in or around the capsule of a grossly intact implant, and in one case, the tumor was confined exclusively to the implant capsule. In patients with silicone implants, silicone granulomas were identified within the capsule and associated neoplasm despite the integrity of the implant. Six cases were fibromatoses; one was a pleomorphic undifferentiated sarcoma; and one was a fibrosarcoma. None of the patients with fibromatosis was known to have familial adenomatous polyposis (FAP) or Gardner syndrome, although one had Poland syndrome (aplasia of the thorax). One patient with a sarcoma had received radiation 10 years previously for breast carcinoma. Six patients were treated with local excision, one with a wide excision, and one patient with fibromatosis was treated with medical therapy. Median follow-up was 3.2 years (range, 16-92 months). One of the 5 patients with fibromatosis developed 2 recurrences. Neither of the 2 patients with sarcomas has developed metastasis. No patient has died of disease. We conclude that IAMT comprise 2 distinct groups—fibromatosis and sarcoma. Surgical trauma, perhaps occurring in patients with a predisposition to develop desmoid tumors, could account for fibromatosis in this setting. The causal relationship between implants and sarcomas is difficult to assess given the rarity of these tumors and that some may be radiation induced. However, at present, there is insufficient evidence to claim that they are biomaterial related.