[Mammary myofibroblastoma: a clinicopathological analysis of fifteen cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of breast myofibroblastoma. Methods: The clinicopathological data and prognostic information of 15 patients with breast myofibroblastoma diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from 2014 to 2022 were collected. Their clinical characteristics, histological subtypes, immunophenotypes and molecular characteristics were analyzed. Results: There were 12 female and 3 male patients, ranging in age from 18 to 78 years, with a median and average age of 52 years. There were 6 cases in the left breast and 9 cases in the right breast, including 12 cases in outer upper quadrant, 2 cases in inner upper quadrant and 1 case in outer lower quadrant. Most of the cases showed a well-defined nodule grossly, including pushing growth under the microscope in 13 cases, being completely separated from the surrounding breast tissue in 1 case, and infiltrating growth in 1 case. Among them, 12 cases were classic subtype and composed of occasional spindle cells with varying intervals of collagen fiber bundles; eight cases had a small amount of fat; one case had focal cartilage differentiation; one case was epithelioid subtype, in which epithelioid tumor cells were scattered in single filing or small clusters; one case was schwannoma-like subtype, and the tumor cells were arranged in a significant palisade shape, resembling schwannoma, and one case was invasive leiomyoma-like subtype, in which the tumor cells had eosinophilic cytoplasm and were arranged in bundles, and infiltrating into the surrounding mammary lobules like leiomyoma. Immunohistochemical studies showed that the tumor cells expressed desmin (14/15) and CD34 (14/15), as well as ER (15/15) and PR (15/15). Three cases with histologic subtypes of epithelioid subtype, schwannoma-like subtype and infiltrating leiomyoma-like subtype showed RB1 negative immunohistochemistry. Then FISH was performed to detect RB1/13q14 gene deletion, and identified RB1 gene deletion in all three cases. Fifteen cases were followed up for 2-100 months, and no recurrence was noted. Conclusions: Myofibroblastoma is a rare benign mesenchymal tumor of the breast. In addition to the classic type, there are many histological variants, among which the epithelioid subtype is easily confused with invasive lobular carcinoma. The schwannoma-like subtype is similar to schwannoma, while the invasive subtype is easily misdiagnosed as fibromatosis-like or spindle cell metaplastic carcinoma. Therefore, it is important to recognize the various histological subtypes and clinicopathological features of the tumor for making correct pathological diagnosis and rational clinical treatment.

Crizotinib-associated Renal Cyst Formation in a Pediatric Patient With ALK+ Epithelioid Inflammatory Myofibroblastic Sarcoma.

BACKGROUND: Crizotinib is a first-generation tyrosine kinase inhibitor used for anaplastic lymphoma kinase (ALK) positive cancers. Simple and complex renal cyst formation is a rare complication of crizotinib use that has been reported previously in the adult population. CASE: We report a case of a right renal mass in a 17-year-old with ALK-positive epithelioid inflammatory myofibroblastic sarcoma treated with Crizotinib. After cessation of Crizotinib and initiating Alectenib, a second generation ALK inhibitor, the mass decreased in size and the patient remained asymptomatic without evidence of recurrence at three months of follow-up.

Utility of STAT6 and 13q14 deletion in the classification of the benign spindle cell stromal tumors of the breast.

The boundaries of the benign spindle cell stromal tumors of the breast are still confusing. This is the reason why different names are interchangeably used for the same tumor and vice versa the same name for different tumors. Therefore, we studied the immunoexpression of easily available markers, such as CD34, α-smooth muscle actin, and desmin, with the addition of STAT6, as well as the chromosome 13q14 region by fluorescence in situ hybridization analysis in a series of 19 cases of benign spindle cell stromal tumors of the breast. Based on the morphologic and immunohistochemical findings, the following histotypes were identified: (i) tumors (10/19 cases) with the characteristic morphology of myofibroblastoma and stained with vimentin, CD34, desmin, and α-smooth muscle actin; (ii) fibroblastic benign spindle cell tumors (5/19 cases) composed of fibroblast-like cells stained only with vimentin and CD34; (iii) tumors (2/19 cases) with the typical morphologic features of solitary fibrous tumor and stained with vimentin, CD34, and STAT6; (iv) 1 case of spindle cell lipoma stained with vimentin and CD34; and (v) 1 case of fibroma composed of a paucicellular, diffusely hyalinized stroma with expression of vimentin and CD34. Notably most of the tumors, with the exception of solitary fibrous tumor, showed monoallelic deletion of FOXO1. This finding supports that myofibroblastoma, fibroblastic benign spindle cell tumor, spindle cell lipoma, and fibroma of the breast are histogenetically related lesions which belong to the same tumor entity.

Inflammatory Myofibroblastic Tumor Associated With the Placenta: Short Tandem Repeat Genotyping Confirms Uterine Site of Origin.

Inflammatory myofibroblastic tumor (IMT) is a neoplasm of intermediate malignant potential that only rarely involves the gynecologic tract. Several cases of IMT arising in various locations including the lung, bladder, trachea, and breast in association with pregnancy have been reported in the literature, and 3 cases involving the placenta have been previously described. We report 2 cases of IMT identified in association with pregnancy; the first was an intrauterine mass delivered entirely separate from the placenta and fetus, and the second was an incidental mass identified within the placental parenchyma following delivery. Short tandem repeat genotyping was used to compare tissue from the tumor and the placenta for both cases. Both tumors were determined to be of maternal origin, confirming that uterine IMTs may present within the placenta or as a separate mass following delivery. This demonstrates the utility of short tandem repeat genotyping in determining the origin of tumors presenting in association with the placenta.

[A peculiar intra-uterine lesion: Inflammatory myofibroblastic tumor (IMT)]. / Une lésion intra-utérine atypique : tumeur myofibroblastique inflammatoire (TMI).

A 25-year-old woman presented with a spontaneous vaginal expulsion of a 4cm well-circumscribed nodule a few weeks after delivery. An inflammatory myofibroblastic tumor diagnosis was made by morphologic, immunohistochemistry and FISH analysis of the nodule.

Myofibroblastic, fibroblastic and myoid lesions of the breast.

Myofibroblastic, fibroblastic and/or myoid lesions are rare in the breast but comprise the majority of mammary mesenchymal spindle cell lesions. Whereas most have similar features to their counterparts at extramammary sites, pseudoangiomatous stromal hyperplasia is considered a breast-specific myofibroblastic proliferation on the same spectrum as myofibroblastoma. Other lesions with myofibroblastic/fibroblastic differentiation include fibromatosis and nodular fasciitis, as well as more aggressive tumors such as the rarely reported myofibrosarcoma, inflammatory myofibroblastic tumor and fibrosarcoma. Lesions with myoid differentiation include benign leiomyoma, myoid hamartoma and leiomyomatous myofibroblastoma, but primary leiomyosarcoma and rhabdomyosarcoma may also rarely arise in the breast. Furthermore, fibroepithelial lesions and metaplastic carcinomas can demonstrate myoid metaplasia. Diagnosis can be challenging, particularly on core biopsy, but benign lesions with or without recurrence potential must be distinguished from more aggressive tumors, especially metaplastic carcinoma and phyllodes tumors. This article will review lesions with myofibroblastic, fibroblastic and myoid differentiation in the breast, with special emphasis on differential diagnosis.

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.

Mammary-type Myofibroblastoma: Clinicopathologic Characterization in a Series of 143 Cases.

Mammary-type myofibroblastoma (MTMF) is a benign mesenchymal neoplasm initially described to occur in the breast. MTMF is typically CD34 and desmin positive and genetically has rearrangement or deletion of 13q14, resulting in loss of Rb expression by immunohistochemistry (IHC). Although the wider anatomic distribution of MTMF is increasingly recognized, no large series with clinicopathologic information has been reported to date. Archival cases were retrieved, and the diagnosis of MTMF was confirmed. Hematoxylin and eosin-stained slides and IHC slides were reviewed when available (CD34, Desmin, Rb, SMA, S100, EMA, MDM2, CDK4). The patient age, sex, tumor anatomic location and size, preceding symptoms, and margin status were recorded when possible. Clinical follow-up data were requested for tumor recurrence, metastasis, and patient status at last follow-up. A total of 143 cases of MTMF comprised this study, affecting 94 (66%) male and 49 (34%) female individuals. Mean tumor size was 6.6 cm (range, 1 to 22 cm). Anatomic locations included: inguinal/groin region (65; 45%), breast (15; 10%), chest wall/axilla (7; 5%), trunk (17; 12%), lower (18; 13%) and upper (2; 1%) extremities, or intra-abdominal/retroperitoneal (14; 10%). MTMFs were characterized by spindle cells with relatively short, stubby nuclei and a variable adipocytic component. Hyalinization and myxoid stroma were common. Less common morphologic features included nuclear atypia, epithelioid tumor cell morphology, and neurilemmoma-type nuclear palisading. CD34 and desmin were positive in 89% and 91%, respectively, and were both negative in 3%. Rb expression was lost in 92% (57/62). No cases with follow-up data available had tumor recurrence, although 1 case was reportedly a recurrence itself. In summary, MTMF appears more common at extramammary sites than in the breast and can cause diagnostic difficulty when atypia or epithelioid morphology is present or when located in an unusual anatomic location. MTMF is frequently positive for CD34 and desmin by IHC; however, rare cases are negative for both. There is no evidence of any significant recurrence risk for MTMF, even in the presence of positive resection margins. The degree of morphologic overlap between spindle cell lipoma, cellular angiofibroma, and MTMF, in combination with shared genetics and slightly overlapping anatomic distribution, raises the question of whether or not these tumors are truly distinct entities or instead represent points along a single spectrum of genetically related tumors.

Novel PAX3-NCOA1 Fusions in Biphenotypic Sinonasal Sarcoma With Focal Rhabdomyoblastic Differentiation.

Sarcomas arising in the sinonasal region are uncommon and encompass a wide variety of tumor types, including the newly described biphenotypic sinonasal sarcoma (BSNS), which is characterized by a monomorphic spindle cell proliferation with dual neural and myogenic phenotypes. Most BSNSs harbor a pathognomonic PAX3-MAML3 fusion driven by t(2;4)(q35;q31.1), whereas the alternative fusion partner gene remains unidentified in a subset of PAX3-rearranged cases. As NCOA1 on 2p23 is a known partner in PAX3-related fusions in other tumor types (ie, alveolar rhabdomyosarcoma), we investigated its status by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction assays in 2 BSNS cases showing only PAX3 gene rearrangements. Novel PAX3-NCOA1 fusions were identified in these 2 index cases showing an inv(2)(q35p23) by FISH and confirmed by reverse transcription polymerase chain reaction. Five additional BSNS cases with typical morphology were studied by FISH, revealing a PAX3-MAML3 fusion in 4 cases and only PAX3 rearrangement in the remaining case without abnormalities in MAML3 or NCOA1 gene. Except for 1 case with surface ulceration, all other tumors lacked increased mitotic activity or necrosis, and all cases immunohistochemically coexpressed S100 protein and actin, but lacked SOX10 reactivity. Interestingly, the 2 PAX3-NCOA1-positive cases showed desmin reactivity and displayed a small component of rhabdomyoblastic cells, which were not seen in the more common PAX3-MAML3 fusion cases. In conclusion, we report a novel PAX3-NCOA1 fusion in BSNS, which appears to be associated with focal rhabdomyoblastic differentiation and should be distinguished from PAX3-NCOA1-positive alveolar rhabdomyosarcoma or malignant Triton tumor. SOX10 immunohistochemistry is a useful marker in distinguishing BSNS from peripheral nerve sheath tumors.

Epithelioid Myofibroblastoma of the Breast: A Report of Two Cases with Discussion of Diagnostic Pitfalls.

Mesenchymal lesions of the breast are uncommon lesions which present diagnostic dilemmas for even the most experienced pathologists. Here, we present two cases of the epithelioid-variant of myofibroblastoma which were misdiagnosed as malignant lesions. Careful integration of clinical presentation, imaging, and close examination of the gross, histologic, and immunohistochemical findings can assist in differentiating these challenging lesions and avoiding diagnostic pitfalls.

The Juscelino Kubitschek government and the Brazilian Malaria Control and Eradication Working Group: collaboration and conflicts in Brazilian and international health agenda, 1958-1961 / O governo JK e o Grupo de Trabalho de Controle e Erradicação da Malária no Brasil: encontros e desencontros nas agendas brasileira e internacional de saúde, 1958-1961

Malaria, a disease which was under control in the beginning of Juscelino Kubitschek government, became the most important endemic disease in 1958, when Brazil made a commitment with the World Health Organization to convert its control programs into eradication programs. For this purpose a Malaria Control and Eradication Group was set up under the leadership of the malaria specialist Mário Pinotti. Malaria would become an important bargaining chip in the context of the development policies of Kubitschek. This article focuses on path of the Malaria Control and Eradication Working Group in Brazil, in its varying relationships with the arguments and guidelines established at international level.

A malária, doença que estava controlada no início do governo de Juscelino Kubitschek, torna-se a mais importante endemia em 1958, quando o Brasil assumiu o compromisso com a Organização Mundial da Saúde de converter seus programas de controle em programas de erradicação. Para isso foi instalado um Grupo de Controle e Erradicação da Malária sob a direção do malariologista Mário Pinotti. A malária seria uma importante moeda de negociação no contexto da política de desenvolvimento de Kubitschek. Este artigo tem como foco a trajetória do Grupo de Trabalho de Controle e Erradicação da Malária no Brasil, em suas diferentes relações com as discussões e normativas travadas e estabelecidas em âmbito internacional.

Lipomatous myofibroblastoma of the breast: case report with diagnostic and histogenetic considerations.

We report rare case of myofibroblastoma (MFB) of the breast comprised predominantly of a mature fatty component, representing approximately 70% of the entire tumour area. This tumour, designated "lipomatous MFB", should be interpreted as the morphological result of an unbalanced bidirectional differentiation of the precursor mammary stromal cell, with the adipocytic component overwhelming the fibroblastic/myofibroblastic one. Lipomatous MFB is a rare variant of mammary MFB, which can mimic malignancy because of the close juxtaposition of fibroblasts/myofibroblasts with mature adipocytes, resulting in a finger-like infiltrative growth pattern of the former towards the latter. Histogenetic considerations and differential diagnostic problems with other bland-looking spindle cell tumours containing infiltrating fat are provided.

Giant pelvic angiomyofibroblastoma: case report and literature review.

Angiomyofibroblastoma (AMF) is a rare, benign, soft-tissue tumor, which predominantly occurs in the vulvovaginal region of middle-aged women. It is clinically important to distinguish an AMF from other stromal cell lesions. Here, we report the case of a 32-year-old woman with a rare, giant pelvic AMF, which showed a benign clinical course. The tumor was located in the cul-de-sac of Douglas. It was well demarcated, hypocellular, edematous and composed of spindle-shaped and oval stromal cells aggregating around thin-walled blood vessels. The tumor cells had abundant eosinophilic cytoplasm, and expressed estrogen receptors, progesterone receptors and desmin. Mitotic figures were absent. It is important to distinguish AMFs from aggressive angiomyxomas because both occur at similar sites but show different clinical behaviors. Most AMFs and aggressive angiomyxomas have the same immunohistochemical phenotype. The well-circumscribed borders of AMF are the most important characteristic that distinguish it from aggressive angiomyxomas. AMFs rarely recur after complete surgical excision. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5510813471244189.

Myofibroblastoma of the breast with smooth muscle differentiation showing deletion of 13q14 region: report of a case.

Breast myofibroblastomas are rare benign mesenchymal tumors belonging to the group of stromal breast tumors composed of spindle-shaped cells and characterized by a broad morphologic spectrum. Among the different morphologic variants described, breast MFBs can show smooth muscle cell differentiation in very rare cases. In terms of the genetic abnormalities found in this type of tumor, a deletion of chromosome 13q14 was recently confirmed by FISH in some cases of mammary MFB. In this paper, we report an unusual case of MFB with smooth muscle differentiation showing a deletion of chromosome 13q14.

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.

Atypical epithelioid cell myofibroblastoma of the breast with multinodular growth pattern: a potential pitfall of malignancy.

Myofibroblastoma (MFB) of the breast is the prototypical benign spindle cell tumor arising from the mammary stroma. Over the last two decades, several morphological variants of this tumor have been recognized. Epithelioid cell MFB is composed predominantly of neoplastic elements with epithelioid morphology. It represents a potential diagnostic pitfall of malignancy, especially when evaluating small biopsies. We report a unique case of a mammary epithelioid cell MFB composed of large mono- to multi-nucleated cells showing mild to moderate nuclear pleomorphism, predominantly arranged in a multinodular growth pattern. This tumor needs to be distinguished from invasive apocrine, oncocytic, pleomorphic lobular carcinoma, as well as metastases. Immunohistochemistry revealed the fibroblastic/myofibroblatic (positivity for vimentin, desmin, CD34 and focally for α-smooth muscle actin) nature of proliferating cells, and therefore was crucial for a correct diagnosis.

Inflammatory myofibroblastic tumor of the liver.

 Hepatic inflammatory myofibroblastic tumors are uncommon low grade malignant neoplasms. They can be confused clinically and by imaging studies with abscess.