Primary Smooth Muscle Tumor of Breast: An Unusual Case Presentation

Abstract Introduction Primary smooth muscle tumors (SMT) of the breast are rare with leiomyosarcomas representing less than 0.1% of all malignant breast tumors. Case Presentation A 58-year-old female with no significant past medical history noted on screening mammography to have a circumscribed 6-mm nodule in the right breast, upper outer quadrant. Core needle biopsy showed a spindle cell neoplasm with smooth muscle differentiation. The excisional biopsy showed a 6-mm lesion composed of atypical hyperchromatic spindle cells in fascicles, marked nuclear pleomorphism, and 5 mitoses per 10 high-power fields. By immunohistochemistry, the spindle cells were positive for smooth muscle actin, desmin, and negative for S-100 and cytokeratin AE1/AE3. Positron emission tomography/computed tomography of head/neck, chest, abdomen, and pelvis did not identify other neoplasms. Despite the lesion size, findings were supportive of a leiomyosarcoma. Discussion Breast SMTs have nonspecific clinical or imaging features. Histologically, these present as spindle cell tumors with smooth muscle differentiation. Initial workup starts with distinction between benign and malignant neoplasms. The malignant SMTs are usually large tumors with cytologic atypia and mitotic activity used as diagnostic criteria. In addition, the distinction between primary and metastasis is important and frequently relies on clinical history and exclusion of other primary origins by radiographic survey. In the current case, although the tumor size is unusually small, the histological features and absence of other primary malignancies support the diagnosis of a leiomyosarcoma. Conclusion Primary leiomyosarcoma of breast is extremely uncommon with less than 70 cases reported in the literature. Although they are usually large tumors, this diagnosis should be included in the differential diagnosis when smooth muscle differentiation, significant atypia, and mitoses are encountered in a spindle cell tumor of the breast.

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Abdominal Inflammatory Myofibroblastic Tumor: Minimal Inflammatory Infiltrate and Diffuse Immunoreactivity for Caldesmon are Potential Diagnostic Pitfalls

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.126 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S58-S59

Author(s):

M Alawad ◽

A Dehghani ◽

D Levitan ◽

K Cruickshank

Keyword(s):

Smooth Muscle ◽

Inflammatory Myofibroblastic Tumor ◽

Inflammatory Infiltrate ◽

Inflammatory Pseudotumor ◽

Gene Rearrangement ◽

Spindle Cell ◽

Muscle Differentiation ◽

Fish Analysis ◽

Spindle Cells ◽

Smooth Muscle Differentiation

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) is an uncommon spindle cell lesion that can involve various organs and occurs in multiple body sites. While older terminology (i.e. inflammatory pseudotumor) suggested otherwise, recent molecular studies point toward a neoplastic pathogenesis for IMTs. Herein, we report a case of an abdominal IMT and discuss the morphologic and immunohistochemical pitfalls pertaining to this entity. Methods A 75-year-old woman presented with complaints of generalized abdominal pain and distention. An abdominal CT scan showed multiple peritoneal masses, the largest of which measured 23 cm. Biopsy revealed compact fascicles of bland spindle cells exhibiting diffuse actin and caldesmon immunoreactivity, consistent with a spindle cell tumor with smooth muscle differentiation. Mitotic activity was low-to-unapparent. Surgical excision was performed. The cut surface of the tumor was tan-white with hemorrhagic foci. Histopathologic examination of the tumor showed elongated spindle cells set in a loose myxoid stroma rich in blood vessels and a mixed inflammatory infiltrate. Deeper sections of the tumor were more cellular, showing a similar morphology to that seen in the original biopsy, which was virtually devoid of inflammatory cells. Immunohistochemistry showed diffuse staining for desmin, caldesmon, smooth muscle actin, and ALK. FISH analysis showed ALK gene rearrangement in 52% of tumor cells, confirming the diagnosis of IMT. Results Studies in the literature show that IMTs express smooth muscle markers such as SMA (90%) and desmin (50%). However, immunoreactivity for caldesmon is rarely reported. ALK immunoreactivity is seen in about 35–60% of cases, and when gene rearrangement involving ALK is detected the diagnosis can be confirmed. Conclusion Historically, several terms have been used to describe IMTs, including inflammatory pseudotumor and inflammatory pseudosarcomatous fibromyxoid tumor. While the nomenclature consistently implies an inflammatory infiltrate, this tumor could have various morphological patterns with some areas showing very little to absent inflammation, as demonstrated in our case. Hence, making an accurate diagnosis could be challenging on a limited biopsy. Therefore, ALK testing should be included as part of the diagnostic workup of spindle cell neoplasms with smooth muscle differentiation.

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Interstitial Cells of Cajal in Deep Esophageal Leiomyoma

International Journal of Surgical Pathology ◽

10.1177/1066896916660197 ◽

2016 ◽

Vol 25 (1) ◽

pp. 51-53 ◽

Cited By ~ 3

Author(s):

Magnus Hallin ◽

Satvinder Mudan ◽

Khin Thway

Keyword(s):

Smooth Muscle ◽

Interstitial Cells Of Cajal ◽

Spindle Cell ◽

Smooth Muscle Actin ◽

Gastroesophageal Junction ◽

Interstitial Cells ◽

Correct Treatment ◽

Mesenchymal Neoplasms ◽

Spindle Cells ◽

Cells Of Cajal

Gastrointestinal stromal tumors (GISTs) are potentially aggressive mesenchymal neoplasms with spindle cell, epithelioid, or mixed morphology. They typically express CD117, DOG1, and CD34 and can be diffusely and strongly positive for h-caldesmon. Leiomyomas are benign smooth muscle neoplasms that can arise in a variety of visceral and soft tissue sites, including the gastrointestinal tract. We illustrate a case of a neoplasm of the gastroesophageal junction that was clinically suspected to be a GIST. Histology showed a tumor composed of ovoid and spindle cells arranged in short intersecting fascicles, which was positive for desmin, smooth muscle actin, and h-caldesmon, with a prominent interspersed subpopulation of CD117- and DOG1-positive elongated or dendritic-like cells. These features were of leiomyoma with entrapped interstitial cells of Cajal (ICC). The recognition of possible entrapment of ICC in leiomyomas as a potential mimic of GIST is important for correct treatment and prognostication.

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GATA-6 mediates human bladder smooth muscle differentiation: involvement of a novel enhancer element in regulating α-smooth muscle actin gene expression

AJP Cell Physiology ◽

10.1152/ajpcell.00225.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. C1093-C1102 ◽

Cited By ~ 17

Author(s):

Akihiro Kanematsu ◽

Aruna Ramachandran ◽

Rosalyn M. Adam

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Smooth Muscle Actin ◽

Muscle Differentiation ◽

Mrna Levels ◽

Muscle Actin ◽

Bladder Smooth Muscle ◽

Human Bladder ◽

Enhancer Element ◽

Smooth Muscle Differentiation

Hollow organs exposed to pathological stimuli undergo phenotypic modulation characterized by altered expression of smooth muscle contractile proteins and loss of normal function. The molecular mechanisms that regulate smooth muscle differentiation, especially in organs other than the vasculature, are poorly understood. In this study, we describe a role for the GATA-6 transcription factor in regulation of human bladder smooth muscle differentiation. Knockdown of endogenous GATA-6 in primary human bladder smooth muscle cells (pBSMC) led to decreased mRNA levels of the differentiation markers α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin heavy chain. Similar effects were obtained following downregulation of GATA-6 by forskolin-induced elevation of intracellular cAMP levels. Forskolin treatment of pBSMC abolished recruitment of GATA-6 to the α-SMA promoter in vivo and reduced activity of human α-SMA promoter-directed gene expression by >60%. This inhibitory effect was rescued by enforced expression of wild-type GATA-6 but not by a zinc-finger-deleted mutant, GATA-6-ΔZF, which lacks DNA-binding ability. In silico analysis of a region of the human α-SMA promoter, described previously as a transcriptional enhancer, identified a putative GATA-binding site at position −919/−913. Point mutation of this site in SMA-Luc abrogated GATA-6-induced activation of promoter activity. Together, these results provide the first evidence for a functional role for GATA-6 in regulation of bladder smooth muscle differentiation. In addition, these findings demonstrate that GATA-6 regulates human α-SMA expression via a novel regulatory cis element in the α-SMA promoter-enhancer.

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A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation.

The Journal of Cell Biology ◽

10.1083/jcb.103.6.2787 ◽

1986 ◽

Vol 103 (6) ◽

pp. 2787-2796 ◽

Cited By ~ 1122

Author(s):

O Skalli ◽

P Ropraz ◽

A Trzeciak ◽

G Benzonana ◽

D Gillessen ◽

...

Keyword(s):

Monoclonal Antibody ◽

Smooth Muscle ◽

Stromal Cells ◽

Smooth Muscle Actin ◽

Muscle Differentiation ◽

Dermal Fibroblasts ◽

Muscle Actin ◽

Alpha Smooth Muscle Actin ◽

Aortic Media ◽

Smooth Muscle Differentiation

A monoclonal antibody (anti-alpha sm-1) recognizing exclusively alpha-smooth muscle actin was selected and characterized after immunization of BALB/c mice with the NH2-terminal synthetic decapeptide of alpha-smooth muscle actin coupled to keyhole limpet hemocyanin. Anti-alpha sm-1 helped in distinguishing smooth muscle cells from fibroblasts in mixed cultures such as rat dermal fibroblasts and chicken embryo fibroblasts. In the aortic media, it recognized a hitherto unknown population of cells negative for alpha-smooth muscle actin and for desmin. In 5-d-old rats, this population is about half of the medial cells and becomes only 8 +/- 5% in 6-wk-old animals. In cultures of rat aortic media SMCs, there is a progressive increase of this cell population together with a progressive decrease in the number of alpha-smooth muscle actin-containing stress fibers per cell. Double immunofluorescent studies carried out with anti-alpha sm-1 and anti-desmin antibodies in several organs revealed a heterogeneity of stromal cells. Desmin-negative, alpha-smooth muscle actin-positive cells were found in the rat intestinal muscularis mucosae and in the dermis around hair follicles. Moreover, desmin-positive, alpha-smooth muscle actin-negative cells were identified in the intestinal submucosa, rat testis interstitium, and uterine stroma. alpha-Smooth muscle actin was also found in myoepithelial cells of mammary and salivary glands, which are known to express cytokeratins. Finally, alpha-smooth muscle actin is present in stromal cells of mammary carcinomas, previously considered fibroblastic in nature. Thus, anti-alpha sm-1 antibody appears to be a powerful probe in the study of smooth muscle differentiation in normal and pathological conditions.

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Primary Leiomyosarcoma of the Kidney

Pathology Research International ◽

10.4061/2010/652398 ◽

2010 ◽

Vol 2010 ◽

pp. 1-4 ◽

Cited By ~ 5

Author(s):

Kusuma Venkatesh ◽

Monika Lamba Saini ◽

S. R. Niveditha ◽

Chaithra Krishnagiri ◽

Sudarshan Babu

Keyword(s):

Renal Cell Carcinoma ◽

Smooth Muscle ◽

Cell Carcinoma ◽

Renal Cell ◽

Spindle Cell ◽

Smooth Muscle Actin ◽

Abdominal Mass ◽

Left Kidney ◽

Spindle Cells ◽

Primary Leiomyosarcoma

Primary leiomyosarcoma of the kidney is a rare tumor with an aggressive behaviour. A 55-year-old woman presented with a left sided abdominal mass in our outpatient department. Radiologic investigations revealed the mass to be renal in origin with colonic adhesions for which radical nephrectomy and hemicolectomy were done. The tumor completely appeared to replace the left kidney and had a whorled character focally on cut section. Microscopically, spindle cells having malignant features with cigar shaped nuclei were seen. The smooth muscle origin of the cells was confirmed by immunohistochemical positivity for smooth muscle actin. Sarcomatoid variant of the renal cell carcinoma was ruled out as the tumor was negative for cytokeratin. Tumors with spindle cell morphology in the kidney should not always be taken for a sarcomatoid variant of renal cell carcinoma and should be investigated thoroughly.

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Do GISTs Occur in Rats and Mice? Immunohistochemical Characterization of Gastrointestinal Tumors Diagnosed as Smooth Muscle Tumors in The National Toxicology Program

Toxicologic Pathology ◽

10.1177/0192623319845838 ◽

2019 ◽

Vol 47 (5) ◽

pp. 577-584

Author(s):

Kyathanahalli S. Janardhan ◽

Priyanka Venkannagari ◽

Heather Jensen ◽

Mark J. Hoenerhoff ◽

Ronald A. Herbert ◽

...

Keyword(s):

Smooth Muscle ◽

Cell Morphology ◽

Spindle Cell ◽

Smooth Muscle Actin ◽

Gi Tract ◽

Toxicological Studies ◽

Smooth Muscle Tumors ◽

Hematoxylin And Eosin ◽

Cells Of Cajal ◽

Rats And Mice

The majority of the tumors in the gastrointestinal (GI) tract of rats and mice, with spindle cell morphology, are diagnosed as smooth muscle tumors (SMTs). Similarly, several decades ago human GI tumors with spindle cell morphology were also diagnosed as SMTs. However, later investigations identified most of these tumors in humans as gastrointestinal stromal tumors (GISTs). The GISTs are considered to arise from the interstitial cells of Cajal located throughout the GI tract. Positive immunohistochemical staining with CKIT antibody is a well-accepted diagnostic marker for GISTs in humans. Since there is a considerable overlap between the histomorphology of SMTs and GISTs, it is not possible to distinguish them on hematoxylin and eosin stained sections. As a result, GISTs are not routinely diagnosed in toxicological studies. The current study was designed to evaluate the tumors diagnosed as leiomyoma or leiomyosarcoma in the National Toxicology Program’s 2-year bioassays using CKIT, smooth muscle actin, and desmin immunohistochemistry. The results demonstrate that most of the mouse SMTs diagnosed as leiomyoma or leiomyosarcoma are likely GISTs, whereas in rats the tumors are likely SMTs and not GISTs.

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