ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1‐ALK fusions in epithelioid inflammatory myofibroblastic sarcoma

ALK oncogenic activation mechanisms were characterized in four conventional spindle‐cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4‐ALK fusions (two cases) or DCTN1‐ALK fusions (two cases), whereas two atypical spindle‐cell IMT had TFG‐ALK and TPM3‐ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2‐ALK fusions in two cases, and a novel RRBP1‐ALK fusion in one case. The epithelioid inflammatory myofibroblastic sarcoma with RRBP1‐ALK fusion had cytoplasmic ALK expression with perinuclear accentuation, different from the nuclear membranous ALK localization in epithelioid inflammatory myofibroblastic sarcomas with RANBP2‐ALK fusions. Evaluation of three additional uncharacterized epithelioid inflammatory myofibroblastic sarcomas with ALK cytoplasmic/perinuclear‐ accentuation expression demonstrated RRBP1‐ALK fusion in two cases. These studies show that atypical spindle‐cell IMT can utilize the same ALK fusion mechanisms described previously in conventional IMT, whereas in clinically aggressive epithelioid inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic mechanism, resulting from fusion with the RRBP1 gene. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors

Inflammatory myofibroblastic tumors (IMTs) are neoplastic mesenchymal proliferations featuring an inflammatory infiltrate composed primarily of lymphocytes and plasma cells. The myofibroblastic cells in some IMTs contain chromosomal rearrangements involving the ALK receptor tyrosine-kinase locus region (chromosome band 2p23). ALK-which is normally restricted in its expression to neural tissues-is expressed strikingly in the IMT cells with 2p23 rearrangements. We now report a recurrent oncogenic mechanism, in IMTs, in which tropomyosin (TPM) N-terminal coiled-coil domains are fused to the ALK C-terminal kinase domain. We have cloned two ALK fusion genes, TPM4-ALK and TPM3-ALK, which encode approximately 95-kd fusion oncoproteins characterized by constitutive kinase activity and tyrosylphosphorylation. Immunohistochemical and molecular correlations, in other IMTs, implicate non-TPM ALK oncoproteins that are predominantly cytoplasmic or pre- dominantly nuclear, presumably depending on the subcellular localization of the ALK fusion partner. Notably, a TPM3-ALK oncogene was reported recently in anaplastic lymphoma, and TPM3-ALK is thereby the first known fusion oncogene that transforms, in vivo, both mesenchymal and lymphoid human cell lineages.     

Inflammatory myofibroblastic tumor of the uterus with prominent myxoid change

A surgical case of inflammatory myofibroblastic tumor arising in the uterine corpus and exhibiting prominent myxoid change of the stroma is reported. The patient was a 63-year-old woman with a large tumor mass that filled the uterine cavity and measured 11 cm in maximal dimension. The tumor had a gelatinous appearance and consisted of a loose proliferation of stellate or polygonal cells on a myxomatous background. Fascicular proliferation of spindle cells was also observed focally, and a chronic inflammatory cell infiltration was seen in many areas. Tumor cells had mild atypism and were immunoreactive for vimentin, alpha-smooth muscle actin, and anaplastic lymphoma kinase (ALK). Focal immunoreactivity for high-molecular-weight caldesmon (h-caldesmon) was also noted. The patient has been free from recurrence for 8 months. Inflammatory myofibroblastic tumor of the uterus occasionally shows prominent myxoid change of the stroma, and differentiation from myxoid leiomyosarcoma is problematic in these cases. Based on the immunoreactivity of tumor cells for ALK and h-caldesmon, the present tumor was considered inflammatory myofibroblastic tumor showing a focal phenotypic transition from myofibroblasts to smooth muscle cells.     

Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal proliferation of transformed myofibroblasts, with a prominent inflammatory cell component, that can mimic other spindle cell processes such as nodular fasciitis, desmoid tumor, and gastrointestinal stromal tumor. Genetic analyses have recently demonstrated rearrangements of anaplastic lymphoma kinase (ALK), located at 2p23, in a subset of IMTs. Molecular characterizations have identified ALK fusions involving tropomyosin-3 and -4 (TPM-3 and -4), the clathrin heavy chain (CLTC), and the cysteinyl-tRNA synthetase (CARS) genes as fusion partners. Here we describe two IMTs with a novel ALK fusion that involves the Ran-binding protein 2 (RANBP2) gene at 2q13, which normally encodes a large (358-kDa) nucleopore protein localized at the cytoplasmic side of the nuclear pore complex. The N-terminal 867 residues of RANBP2 are fused to the cytoplasmic segment of ALK in the 1,430-amino acid RANBP2-ALK chimeric protein. Myofibroblasts that express RANBP2-ALK exhibit nuclear membrane-associated ALK staining that is unique compared to the subcellular localization observed with other ALK fusions in IMT, presumably attributable to heteroassociation of the fusion with normal RANBP2 at the nuclear pore. These findings expand the spectrum of ALK abnormalities observed in IMT and further confirm the clonal, neoplastic nature of these lesions.     

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.     

Identification of novel fusion partners of ALK,the anaplastic lymphoma kinase,in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor

ALK-positive anaplastic large-cell lymphoma (ALCL) has been recognized as a distinct type of lymphoma in the heterogeneous group of T/Null-ALCL. While most of the ALK-positive ALCL (ALKomas) are characterized by the presence of the NPM-ALK fusion protein, the product of the t(2;5)(p23;q35), 10-20% of ALKomas contain variant ALK fusions, including ATIC-ALK, TFG-ALK, CLTC-ALK (previously designated CLTCL-ALK), TMP3-ALK, and MSN-ALK. TMP3-ALK and TMP4-ALK fusions also have been detected in inflammatory myofibroblastic tumors (IMTs), making clear that aberrations of the ALK gene are not associated exclusively with the pathogenesis of ALK-positive ALCL. Here we report results of molecular studies on two lymphoma cases and one IMT case with variant rearrangements of ALK. Our study led to the detection of the CLTC-ALK fusion in an ALCL case and to the identification of two novel fusion partners of ALK: ALO17 (KIAA1618), a gene with unknown function, which was fused to ALK in an ALCL case with a t(2;17)(p23;q25), and CARS, encoding the cysteinyl-tRNA synthetase, which was fused to ALK in an IMT case with a t(2;11;2)(p23;p15;q31). These results confirm the recurrent involvement of ALK in IMT and further demonstrate the diversity of ALK fusion partners, with the ability to homodimerize as a common characteristic.     

ALK expression in pseudosarcomatous myofibroblastic proliferations of the genitourinary tract

AIMS: Pseudosarcomatous myofibroblastic proliferation of the genitourinary tract is rare and may develop after trauma or spontaneously. The aim of this study was to characterize further the clinicopathological features of these lesions and to examine their relationship to inflammatory myofibroblastic tumour (IMT). METHODS AND RESULTS: Twenty-seven cases of pseudosarcomatous myofibroblastic proliferation were analysed. There were seven males and 20 females; median age was 37 years (range 16-88). Most lesions were from the bladder (n = 21), while others were in the urethra, vulva, vagina, rectum and retrovesical space. Median tumour size was 30 mm (range 6-120 mm). Seven cases (25%) had a history of prior trauma or surgery. Three cases recurred locally but not destructively. The tumours had fasciitis-like features including bland spindle cells with evenly distributed chromatin, admixed inflammatory cells (mainly lymphocytes) and often a myxoid stroma. Immunohistochemistry showed positivity for smooth muscle actin in 14/20 cases, keratin in 8/19, desmin in 7/20 and anaplastic lymphoma kinase (ALK) in 10/21 cases. Fluorescent in situ hybridization was performed in six ALK+ cases; all were negative for ALK gene rearrangement. CONCLUSIONS: Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract may show ALK immunopositivity but do not show consistent ALK rearrangement. Given subtle morphological differences and more consistently benign behaviour, their relationship to inflammatory myofibroblastic tumour at other sites remains uncertain.     

Intraocular inflammatory myofibroblastic tumor with ALK overexpression

We report a case of an intraocular inflammatory myofibroblastic tumor nearly filling the vitreous cavity of the eye of a 50-year-old man. The tumor was composed of a mixture of spindle cells and mixed inflammatory elements, including numerous plasma cells. The differential diagnosis included inflammatory pseudotumor and neoplastic mimics of this condition. Further investigation with immunohistochemistry revealed the mass to be composed of myofibroblasts, positive for smooth muscle actin stains and with weak anaplastic lymphoma kinase (ALK) expression in some tumor cells. Evaluation by fluorescence in situ hybridization revealed the tumor cells to have multiple copies of chromosome 2 and ALK but no rearrangement of the ALK gene. The authors propose that multiple copies of the ALK gene may be involved in inflammatory myofibroblastic tumor tumorigenesis, in addition to ALK gene rearrangements.     

炎性肌纤维母细胞肿瘤临床病理学分析

目的探讨炎性肌纤维母细胞肿瘤(inflammatory myofibroblastic tumor,IMT)的临床病理学特征、诊断与鉴别诊断要点。方法收集江苏省人民医院病理科2010年5月至2020年5月诊治的32例IMT,观察其临床及组织病理学、免疫组织化学及分子病理特点,并复习相关文献。结果患者男19例,女13例,年龄5~65岁(平均年龄37岁)。肺及纵隔10例,胃肠道、肠系膜/大网膜12例,膀胱5例,头颈部3例,小腿软组织及腹膜后各1例,其中4例为上皮样炎性肌纤维母细胞肉瘤(epithelioid inflammatory myofibroblastic sarcoma,EIMS),均位于腹腔。组织学肿瘤以梭形肌纤维母细胞及纤维母细胞增生为主,间质不同程度疏松水肿黏液变至胶原化,伴多少不等的慢性及急性炎性细胞浸润;EIMS以上皮样瘤细胞为主,间质水肿黏液变,浸润炎性细胞主要为中性粒细胞。免疫组织化学:肿瘤细胞表达间变性淋巴瘤激酶(ALK,25/32,78%),除4例EIMS均为核膜阳性外,其余IMT均为胞质阳性;肿瘤细胞还表达广谱细胞角蛋白(8/19)、平滑肌肌动蛋白(24/32,75%)、结蛋白(12/32,38%),其中4例EIMS均为结蛋白强阳性。15例行ALK荧光原位杂交检测显示12例(12/15)可见分离信号,以非经典断裂信号为主。3例行二代测序显示1例小腿IMT出现CLIP2-ALK融合,2例EIMS均示RANBP2-ALK融合。随访29例,22例无瘤生存,4例复发(其中3例克唑替尼治疗并带瘤生存),3例死亡(其中2例为EIMS)。结论IMT形态学谱系广泛,需与多种良恶性肿瘤鉴别,免疫组织化学(抗体ALKp80、ALKD5F3)及荧光原位杂交检测(ALK断裂探针)可辅助IMT的诊断,不典型病例推荐二代测序检测。     

Vocal cord inflammatory myofibroblastic tumor with mucoid deposits harboring TIMP3–ALK fusion: A potential diagnostic pitfall

A 35‐year‐old Japanese man who had experienced hoarseness for 10 years presented with a vocal cord lesion. A gross examination revealed a left vocal cord polyp occupying two‐thirds of the vocal space. The endoscopically resected lesion contained scattered atypical fibroblastic, stellate, or ganglion‐like cells with mucoid stroma. Vacuolated cells were also seen. Lymphoplasmacytic infiltrate was largely undetectable. A vocal cord polyp was first suspected, but well‐differentiated liposarcoma and inflammatory myofibroblastic tumor (IMT) were included in the differential diagnoses. The tumor cells were positive for anaplastic lymphoma kinase (ALK), calponin, and vimentin, and negative for other smooth muscle markers by immunohistochemistry. Structures resembling myofibroblasts were not observed by electron microscopy, which confirmed abundant rough endoplasmic reticulum in the tumor cells and accumulated lipid droplets in some tumor cells. ALK gene rearrangement was detected by fluorescence in situ hybridization, and TIMP3–ALK fusion was confirmed by 5′ rapid ampli?cation of cDNA ends. We diagnosed the lesion as an IMT, and an ALK‐rearranged stellate cell tumor may be postulated. This is the first report of a fusion partner gene of ALK in a case of laryngeal IMT.     

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.     

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.     

Inflammatory pseudotumor (inflammatory myofibroblastic tumor) of the mitral valve of the heart

We report a rare case of inflammatory pseudotumor/inflammatory myofibroblastic tumor (IPT/IMT) of the heart, involving the mitral valve. A 58‐year‐old woman presenting with dyspnea was immediately admitted to the hospital, and found to have congestive heart failure due to the invagination of a tumor‐like mass of the mitral valve. This mass arose from and involved almost the entire posterior leaflet of the mitral valve and occupied almost the entire mitral valve orifice. The tumor was a yellowish‐white well‐circumscribed mass with a smooth surface. The excised mass was 3.0 × 2.3 × 1.8 cm, and consisted of abundant Sudan III‐positive foam cells, histiocytes, lymphocytes, plasma cells, and loosely arrayed spindle cells, in vascular‐rich fibrous tissue. Immunohistochemistry showed that the spindle cells were positive for vimentin and α‐smooth muscle actin, and negative for desmin, CD34, and human muscle actin (HHF‐35), suggesting they were myofibroblastic cells. The plasma cells and lymphocytes showed no monoclonality. There were few mitotic cells, and, except for the lymphocytes, few Ki‐67‐positive cells. The findings suggested IPT/IMT. The 39 cardiac IPT/IMT cases appearing in the English‐language literature are discussed.     

Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor

Inflammatory myofibroblastic tumor (IMT) is a rare, but distinctive mesenchymal neoplasm composed of fascicles of bland myofibroblasts admixed with a prominent inflammatory component. Genetic studies of IMTs have demonstrated chromosomal abnormalities of 2p23 and rearrangement of the anaplastic lymphoma kinase (ALK) gene locus. In a subset of IMTs, the ALK C-terminal kinase domain is fused with a tropomyosin N-terminal coiled-coil domain. In the current study, fusion of ALK with the clathrin heavy chain (CTLC) gene localized to 17q23 was detected in two cases of IMT. One of these cases exhibited a 2;17 translocation in addition to other karyotypic anomalies [46,XX,t(2;17)(p23;q23),add(16)(q24)].     

Inflammatory myofibroblastic tumor and low-grade myofibroblastic sarcoma: a comparative study of clinicopathologic features and further observations on the immunohistochemical profile of myofibroblasts

Inflammatory myofibroblastic tumor (IMT) and low-grade myofibroblastic sarcoma (LGMS) are intermediate- or low-grade malignant myofibroblastic neoplasms. In this study, the clinicopathologic profiles of 24 IMTs and 10 LGMS were compared with a focus on the immunohistochemical profiles of the neoplastic myofibroblasts. The primary antibodies used in this study were specific for the ultrastructural subcellular components: (1) *-smooth muscle actin (*-SMA), muscle-specific actin (MSA), calponin, and h-caldesmon for myofilaments; (2) fibronectin for fibronexus; (3) laminin for basal lamina; (4) desmin and cytokeratin for intermediate filaments. Anaplastic lymphoma kinase (ALK) alterations were examined by immunohistochemical means, with selective fluorescence in situ hybridization analysis. Histologically, IMT had inhomogeneous microscopic features with multi-component and multi-patterned architecture, whereas LGMS tended to be more uniform in appearance with a higher cellularity, more prominent nuclear hyperchromasia, and a more widely infiltrative growth pattern than IMT. Immunohistochemically, firstly, more than 90% of the cases of both IMT and LGMS expressed calponin, *-SMA, MSA, and fibronectin, almost all with a high expression level, and no cases were positive for h-caldesmon. Secondly, 33.3% (7/21) of IMTs and 40% (4/10) of LGMS were positive for desmin with a low expression level. The positive percentage for laminin was 81.8% (18/22) in IMT, but was 42.9% (3/7) in LGMS with a low expression level. Thirdly, 13.6% (3/22) of IMTs were positive for cytokeratin, but no expression was found in LGMS. ALK staining was found in 40.9% (9/22) of IMTs, and the presence of ALK gene rearrangements was confirmed by fluorescence in situ hybridization in 5 of 6 IMTs examined. However, neither ALK gene rearrangements nor ALK protein labeling was detected in LGMS (0/9). In summary, IMT and LGMS are both composed of cells displaying well-developed myofibroblastic differentiation, which frequently and extensively express actin-associated proteins (*-SMA, MSA, and calponin) and fibronectin, consistent with the ultrastructure markers (myofilaments and fibronectin fibrils). Laminin expression does not exclude a diagnosis of myofibroblastic neoplasms. ALK and cytokeratin, when positive, can be helpful in differentiating IMT from LGMS. LGMS is not a member of the family of ALK-positive tumors.     

Myofibroblastic sarcomas: a brief review of sarcomas showing a myofibroblastic line of differentiation and discussion of the differential diagnosis

Although myofibroblasts have been intensively studied during the last three decades there is still a lack of consensus regarding their exact role and position in the spectrum of proliferative and neoplastic spindle cell lesions. This especially concerns the question of whether myofibroblastic neoplasms, or in other words a myofibroblastic line of differentiation in mesenchymal neoplasms, exist or not. Some authors question the existence of benign and particularly malignant myofibroblastic neoplasms, and suggest rather that myofibroblasts represent a functional stage in neoplastic processes arising from fibroblasts, smooth muscle cells or pericytes. It has been claimed that the ultrastructural evidence of so-called fibronexus (microtendons) and stress fibres plays a crucial role in the diagnosis of myofibroblastic neoplasms, and that myofibroblasts are defined essentially by electron microscopy. However, in diagnostic surgical pathology mesenchymal neoplasms are classified according to the cell type they most closely resemble, and it is not surprising that, in neoplastic processes, variable genetic and morphological changes occur. Therefore it seems impractical that a single specialised organelle such as the enigmatic fibronexus should be the limitation for the delineation of a line of differentiation. For practical purposes, myofibroblastic neoplasms are composed of spindle-shaped tumour cells set in a more or less collagenous matrix. Myofibroblastic tumour cells contain ill-defined eosinophilic cytoplasm and fusiform nuclei that are either elongated and wavy or plumper and vesicular. Neoplastic myofibroblasts stain positively for muscle actin, alpha-smooth muscle actin, and/or desmin and are characterised by a variable immunophenotype. Ultrastructurally, myofibroblasts share features of fibroblasts and smooth muscle cells but differ from both cell types. Given these diagnostic criteria it is most likely that, in addition to well-known reactive and benign myofibroblastic proliferations, a variety of clinicopathological forms of myofibroblastic sarcomas (myofibrosarcomas) occur. In this spectrum congenital and infantile fibrosarcoma, inflammatory myofibroblastic tumour, low-grade myofibroblastic sarcoma, and high-grade (‘MFH’-like) myofibroblastic sarcoma are briefly reviewed and their differential diagnosis is discussed.     

腹腔脏器炎性肌纤维母细胞瘤的临床病理观察

目的探讨腹腔脏器炎性肌纤维母细胞瘤(inflammatorymyofibroblastictumor,IMT)的临床病理特征、组织发生和预后。方法分析10例IMT的临床病理学资料,所有病例行HE染色和免疫组化染色。结果腹腔脏器IMT的组织学分为三型:(1)黏液样-血管型,(2)梭型细胞密集型,(3)少细胞纤维瘢痕型。肿瘤细胞表达vimentin、SMA、MSA、CKpan和ALK,其阳性率分别为100%、90%、90%、60%和20%。10例IMT中有5例做了根治性切除术,另有5例单纯肿瘤切除,随访无1例复发。结论腹腔脏器IMT易被临床医师误诊为晚期癌。免疫组化表型是该肿瘤与其他软组织肿瘤鉴别的重要依据。腹腔脏器IMT一般具有良性病变的生物学行为,根治性手术可能治愈。     

Inflammatory myofibroblastic tumour (inflammatory pseudotumour) of the breast. Clinicopathological and genetic analysis of a case with evidence for clonality.

Inflammatory myofibroblastic tumours (IMTs) were initially considered to be benign reactive processes, but cases with an unfavourable outcome have been reported. Moreover, clonal genetic alterations have recently been published in some cases, suggesting that IMT may represent a malignant neoplastic entity. This paper reports a case of IMT that developed in the mammary gland, an unusual site. The histological picture was characterized by a proliferation of spindle cells with little cellular atypia and rare mitoses, associated with a polymorphous inflammatory infiltrate. Their immunophenotype, characterized by the expression of vimentin, smooth muscle actin, and cytokeratins, corresponded to that of myofibroblasts. Cytogenetic analysis revealed the clonal nature of the lesion. The modal karyotype was 48, X, ins(2;X)(q34;p21.2p22.2), +7, del(9)(p23), +19. Including the present observation, a 9p deletion has now been found in three cases of IMT. These observations show that IMT may be a clonal neoplasm, even in sites different from deep soft tissues.