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Background
This is a benign tumor of soft tissue. Most leiomyomas occur in the uterus, so-called fibroids. However, leiomyomas have occurred in nearly every organ and every location in the soft tissue. Under the microscope, they are nearly identical in every site. Clinically, it is one of the soft tissue tumors that present with pain.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Common AGE RANGE-MEDIAN Middle aged Women
DISEASE ASSOCIATIONS CHARACTERIZATION HLRCC SYNDROME (HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CARCINOMA)
*Laboratory of Pathology †Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant familial syndrome characterized by the development of cutaneous and uterine leiomyomas as well as renal tumors. The mutation of this condition has been identified in the fumarate hydratase (FH, 1q42.3-q43) gene. The histology of the renal cancers has not been well described or illustrated because of the newness of the syndrome.
We reviewed 40 renal tumors resected from 38 patients belonging to HLRCC families with proven fumarate hydratase germline mutation. Patients ranged in age from 17 to 75 years of age. Tumors were unilateral in all but 2 cases. The size of the tumors varied between 2.3 and 20 cm and there was no laterality preference. Several different architectural patterns were recognized: papillary (25 cases), tubulo-papillary (8 cases), tubular (2 cases), and solid (1 case). Mixed patterns were also present in 4 cases.
The most important histologic feature of these neoplasms, which we believe to be the hallmark of the HLRCC tumors, is the presence of a characteristic large nucleus with a very prominent inclusion like orangiophilic or eosinophilic nucleolus, surrounded by a clear halo. Immunohistochemical studies did not provide a specific marker for these tumors, however, loss of heterozygosity at 1q32 and 1q42-44 was frequently found. These tumors are associated with poor prognosis and frequent spread to regional lymph nodes.
At the moment, morphology is the best tool to recognize these tumors. Proper diagnosis of this syndrome by the pathologist may assist in early detection of these tumors.
CLINICAL APPEARANCE/GROSS DISEASE VARIANTS CHARACTERIZATION PENIS
*Department of Pathology, University of Arkansas for Medical Sciences ∥Arkansas Childrenʼs Hospital §Department of Urology, Arkansas Childrenʼs Hospital and University of Arkansas for Medical Sciences, Little Rock, AR †Cincinnati Childrenʼs Hospital Medical Center, Cincinnati, OH ‡Boston Childrenʼs Hospital, Harvard Medical School, Boston, MA.
Penile myointimoma is a rare benign myointimal proliferation occurring exclusively within the corpus spongiosum of the glans penis and is most commonly described in adult patients. To date, there is only one reported series of 10 penile myointimomas plus one case report, representing a total of 8 adults and 3 children/adolescents.
We report 5 penile myointimomas occurring in 5 patients less than 18 years of age (age range 4 to 15 y). All patients presented with a mass lesion on the glans penis ranging in size from 0.4 to 1.8 cm. All 5 lesions had the classic morphologic appearance: myointimal proliferation of the preexisting vascular spaces of the corpus spongiosum, creating a multinodular/plexiform architecture.
Immunohistochemically, all stained cases showed strong cytoplasmic immunoreactivity for smooth muscle actin in the lesional cells and a collarette of native smooth muscle highlighted by desmin. None of the lesions appeared completely excised, but all 5 patients were clinically free of disease at last clinical follow-up (2 to 45 mo).
In summary, we report only the second series of this distinctive, relatively rare myointimal proliferation within the corpus spongiosum of the glans penis, expand the number of published cases occurring in the pediatric/adolescent population, and confirm the benign clinical course after a marginal or incomplete excision.A Distinctive Myointimal Proliferation (`Myointimoma') Involving the Corpus Spongiosum of the Glans Penis A Clinicopathologic and Immunohistochemical Analysis of 10 Cases
John F. Fetsch, M.D.; Robert W. Brinsko, M.D.; Charles J. Davis Jr., M.D.; F. Kash Mostofi, M.D.; Isabell A. Sesterhenn, M.D.
From the Departments of Soft Tissue Pathology and Genitourinary Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, U.S.A.
Am J Surg Pathol 2000;24:1524-1530 Abstract quote
This study details the clinicopathologic and immunohistochemical features associated with 10 cases of a distinctive myointimal proliferation involving the corpus spongiosum of the glans penis.
Patients ranged in age from 2 to 61 years old (mean age, 29 yrs) and presented with a mass that varied in size from 0.5 to 1.9 cm in greatest dimension. The process was said to be present from 4 days to more than 6 months before surgical intervention. In each case, microscopic examination revealed almost identical histology. There was a prominent, often occlusive, fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum. The proliferation consisted of stellate-shaped and spindled cells embedded in abundant fibromyxoid matrix. Occasional lesional cells had well-developed myoid characteristics with moderately abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles. Foci with degenerative changes, including ``ghost cell'' morphology, were also present. The myointimal process was extensively immunoreactive for -smooth muscle actin, muscle-specific actin (HHF-35), and calponin, but it was minimally reactive for the D33 and D-ER-11 desmin clones. In contrast, native vascular smooth muscle encompassing the proliferation was strongly immunoreactive for all five markers. The myointimal cells were nonreactive for CD34, S-100 protein, and keratin. Factor VIIIrAg, CD31, and CD34 highlighted intact endothelial cells lining suboccluded vessels, scattered capillaries that penetrated the proliferation, and the normal uninvolved vasculature. The examined specimens were punch, incisional, or excisional biopsies, and in each instance, the process microscopically extended to the tissue margin. Followup data are available for 8 cases (median follow-up interval, 5 yrs 8 mos): one incompletely excised lesion with 6 months follow-up is stable but persistent, one lesion with 10 years follow-up regressed spontaneously after a punch biopsy, and the remaining six lesions have not recurred.
A differential diagnosis of myofibroma, late-stage intravascular (nodular) fasciitis, vascular leiomyoma, and plexiform fibrohistiocytic tumor is discussed.
Retroperitoneal Leiomyomas A Clinicopathologic and Immunohistochemical Study of 56 Cases With a Comparison to Retroperitoneal Leiomyosarcomas
Edina Paal, M.D. ; Markku Miettinen, M.D. , Ph.D.
From the Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC, U.S.A.
Am J Surg Pathol 2001;25:1355-1363 Abstract quote
Most retroperitoneal smooth muscle tumors are believed to be malignant, and leiomyomas are considered very rare.
This study was undertaken to determine the clinicopathologic features and long-term follow-up of 56 tumors diagnosed as retroperitoneal leiomyomas (LM) or smooth muscle tumors with an uncertain malignant potential (SMTUMP) in an effort to correlate their behavior and clinicopathologic features.
These tumors were compared with a series of 11 cases of retroperitoneal leiomyosarcomas (excluding gastrointestinal stromal tumors). Histologic slides and immunohistochemistry for SMA, desmin, S-100 protein, HMB45, CD34, C-KIT, estrogen (ER) and progesterone (PR) receptor proteins, and MIB-1 were analyzed. All tumors diagnosed as LM and all but one SMTUMP were well-differentiated smooth muscle tumors that lacked atypia and coagulative necrosis. There was <1 mitosis per 50 high power field (HPF) in 38 tumors; no tumor had >3 mitoses/50 HPF. Most tumors had a striking resemblance to uterine smooth muscle tumors with common hyaline change and trabecular patterns.
There were 51 females and 5 males ranging in age from 25 to 79 years (mean 45 years, median 43 years). These tumors were typically large, with a mean size of 16.2 cm and weight of 1600 g. Immunohistochemically, all 35 tumors studied were positive for -SMA, 30 of 35 tumors were positive for desmin, and all were negative for CD117, S100 protein, and HMB45 and all but one for CD34. Steroid receptors were commonly present: ER in 20 of 29 cases and PR in 26 of 31 cases in the tumors of female patients. MIB-1 score was <2% in all of 28 cases.
Long-term follow-up (mean 140 months) did not reveal metastases, but two patients had local recurrence; however, neither patient with recurrence demonstrated disease progression in follow-up. By contrast, all 11 leiomyosarcomas had at least mild atypia, and all were ER and PR negative. All cases had MIB-1-positive nuclei, but only four had >10% nuclei positive. Four patients died of disease, four were alive with recurrence, and three had no evidence of disease.
A group of benign leiomyomas can be identified among retroperitoneal smooth muscle tumors. Most of these tumors resemble uterine leiomyomas by histology and positive hormone receptors, and they seem to have a good long-term prognosis with a small potential for local recurrence.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Criteria for malignancy in nonvisceral smooth muscle tumors.Hornick JL, Fletcher CD.
Department of Pathology, Brigham and Women's Hospital, Boston; and Harvard Medical School, Boston, MA.
Ann Diagn Pathol 2003 Feb;7(1):60-6 Abstract quote Reliable prediction of the behavior of smooth muscle tumors is notoriously problematic at many anatomic locations. Relatively few studies have addressed the minimal histologic criteria for malignancy in smooth muscle tumors of soft tissue and the presently available criteria are not only inconsistently applied but also vary at different anatomic sites.
It has been widely believed that the presence of any mitotic activity in a deep-seated smooth muscle tumor should lead to a diagnosis of leiomyosarcoma. Until very recently, the existence of leiomyomas in deep soft tissue has been disputed. Using presently available data, this review examines criteria for malignancy in smooth muscle tumors in each of the following anatomic compartments: deep soft tissue, including retroperitoneum/abdominal cavity; skin; subcutis; and external genitalia.
Distinct criteria for assessing malignancy should be applied to smooth muscle tumors at each of these locations.
VARIANTS Angioleiomyoma Derived from the smooth muscle of subcutaneous vessels
Four types:
Solid
Cavernous
Venous
IntravascularIntravascular angioleiomyoma J Cutan Pathol 1999;26:165 Intravenous leiomyomatosis
Intravenous leiomyomatosis: molecular and cytogenetic analysis of a case.Quade BJ, Dal Cin P, Neskey DM, Weremowicz S, Morton CC.
Departments of Pathology (BJQ, PDC, SW, CCM) and Obstetrics, Gynecology, and Reproductive Biology (DMN, CCM), Brigham and Women's Hospital and Harvard Medical School (BJQ, PDC, SW, CCM), Boston, Massachusetts.
Mod Pathol 2002 Mar;15(3):351-6 Abstract quote Apart from its hormone responsiveness, little about the pathobiology of intravenous leiomyomatosis (IVL), a rare smooth muscle proliferation, is known.
We investigated the cytogenetics and molecular biology of IVL in a 40-year-old female who presented with an abrupt onset of dyspnea. In addition to the intracaval tumor mass composed of histologically benign smooth muscle, four distinct retroperitoneal "fibroids" were cytogenetically investigated. An identical abnormal karyotype, 45,XX,der(14)t(12; 14)(q15;q24),-22, was observed in all five specimens. Fluorescence in situ hybridization revealed three copies of HMGIC (alias HMGA2), two on the normal chromosomes 12 at 12q15, as well as another on the der(14) in the breakpoint region, suggesting that the 12q breakpoint occurred 5' (centromeric) to HMGIC (HMGA2), as has been frequently observed in uterine leiomyoma. Such similarity in chromosomal rearrangements suggests that there may be a pathogenetic relationship between IVL and uterine leiomyomata with t(12;14). Skewed X inactivation was observed in each tumor sample, but not in the myometrium. In each tumor, the lower molecular weight allele of HUMARA was nonrandomly inactivated.
This pattern of X inactivation is most consistent with origin from a single transformation event, and in this regard, IVL more closely resembles disseminated peritoneal leiomyomatosis than typical uterine leiomyomata.
OSSIFIED
- Ossified soft tissue leiomyoma in a patient with sickle cell anemia.
Xu Y, Lacouture M, Petronic-Rosic V, Soltani K, Shea CR.
Section of Dermatology, Department of Medicine, University of Chicago Hospitals, Chicago, IL, USA.
J Cutan Pathol. 2005 Nov;32(10):696-9. Abstract quote
Osseous metaplasia in leiomyomas is extremely rare. Here, we report the case of an ossified subcutaneous leiomyoma in a 34-year-old African American man with sickle cell thalassemia who presented with a painful nodule of the scapular region, which appeared as a heavily mineralized soft tissue mass on chest radiographs.
Histopathologic and immunohistochemical examination of the resected nodule revealed a benign soft tissue leiomyoma composed of intersecting fascicles of spindle cells that strongly expressed smooth muscle actin and caldesmon. Extensive intratumoral calcification and ossification were noticed.
Only eight cases of ossified leiomyoma have been reported, of which two arose in the deep soft tissue. Those cases are briefly reviewed and discussed.PALISADED ANGIOLEIOMYOMA J Cutan Pathol 2000;27:526-528
May show prominent Verocay-like body formation
PILAR LEIOMYOMA Atypical Pilar Leiomyoma Cutaneous Counterpart of Uterine Symplastic Leiomyoma?
Meera Mahalingam, M.D., Ph.D.; Lynne J. Goldberg, M.D.
From the Dermatopathology Section, Department of Dermatology, Boston University School of Medicine Boston, Massachusetts.
Am J Dermatopathol 2001;23:299-303 Abstract quote
Four cases of cutaneous leiomyoma with cytologic atypia are reported. All four cases were adult men ranging in age from 33 to 92 years of age. Clinical diagnoses were diverse and included epidermal inclusion cyst, scar, nevus, dermatofibroma, squamous cell carcinoma, and basal cell carcinoma.
Histological examination of all four lesions revealed a relatively circumscribed, mild to focally moderately cellular, dermal proliferation of large, irregularly shaped spindle cells in a fascicular arrangement. Some cells contained large irregular nuclei and abundant cytoplasm; others were multinucleate. Moderate to focal marked pleomorphism and rare mitotic figures were present, raising the possibility of leiomyosarcoma; however, the sparse mitotic activity and low cellularity did not warrant this diagnosis.
This study suggests that cutaneous leiomyomas may exhibit bizarre or ``symplastic'' patterns analogous to their uterine counterparts.
SYMPLASTIC
Department of Dermatology, Leeds General Infirmary, Leeds, UK.
We describe the case of a cutaneous symplastic leiomyoma in a 37-year-old woman who presented with a 4-year history of a painful slow growing lesion on the left upper arm. The lesion was excised and subjected to histological examination.
A poorly circumscribed lesion was seen in the dermis composed of spindle shaped cells with marked nuclear pleomorphism. No mitotic figures or necrosis were seen. The cells stained strongly positive with desmin and smooth muscle actin, and negative with S100, melan A, MNF116 a mouse monoclonal antibody to cytokeratin and CK5/6. The diagnosis was felt to be in keeping with a cutaneous symplastic leiomyoma, a rarely reported variant of the pilar leiomyoma.
Histologically, it shows features similar to the symplastic variant of uterine leiomyoma with cytological atypia, nuclear pleomorphism and minimal mitotic activity. Although the long-term outlook is probably benign, the presence of cytological atypia and mitoses in any spindle cell tumor is generally a concerning feature and warrants long-term follow up.TRANEXAMIC-ACID ASSOCIATED NECROSIS
Departments of *Pathology †Obstetrics and Gynaecology ‡Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.
INTRODUCTION: Women with menorrhagia have increased levels of plasminogen activators in the endometrium. Tranexamic acid (cyklokapron), an antifibrinolytic agent, is commonly prescribed worldwide to women with menorrhagia, including those with fibroids. Necrosis in uterine leiomyomas may be associated with pregnancy, and progestogen or oral contraceptive use but its association with tranexamic acid has not been investigated. Four hundred ninety patients with uterine leiomyomas in 2004 and 2005 were reviewed. Their ages ranged from 22 to 86 (mean 47.2). One hundred forty-seven (30%) were treated with tranexamic acid.
RESULTS: Infarct-type necrosis was observed in the leiomyomas of 38 patients, 22 of whom had tranexamic acid (15%) whereas the remaining 16 had no drug exposure (4.7%) (odds ratio=3.60; 95% confidence interval: 1.83-6.07; P=0.0003). Two patients who took the drug less than 2 weeks before surgery had early infarcts with appearance resembled coagulative type necrosis. Eleven of the 22 cases of drug-induced necrotic leiomyoma (50%) also showed intralesional thrombus formation, and 4 showed organization of the thrombi.
CONCLUSIONS: Infarct-type necrosis and thrombosis of leiomyoma was more commonly observed in patients treated with tranexamic acid. Although the drug is effective for menorrhagia, clinicians should be aware of the possible complications associated with leiomyoma necrosis such as pain and fever. Distinguishing between types of necrosis may not always be straightforward particularly in early infarcts when the reparative connective tissue reaction between the viable and necrotic cells is not well-developed, resulting in an appearance similar to coagulative necrosis. When the overall gross and microscopic features of a leiomyoma with coagulative necrosis favor a benign lesion, the drug history should be reviewed so that this type of early and healing infarct-type necrosis is considered as the underlying cause of the apparent coagulative necrosis. This may otherwise result in a diagnosis of smooth muscle tumor of uncertain malignant potential, leading to prolonged follow-up and unnecessary further surgical intervention.
SPECIAL STAINS/
IMMUNOPEROXIDASECHARACTERIZATION h-CALDESMON
h-Caldesmon as a specific marker of smooth muscle cell differentiation in some soft tissue tumors of the skin.D'Addario SF, Morgan M, Talley L, Smoller BR.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas; USA Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas; USA Department of Pathology, University of South Florida, Tampa, FL, USA.
J Cutan Pathol 2002 Aug;29(7):426-429 Abstract quote BACKGROUND: An existing problem in contemporary pathology is the classification and distinction of spindle cell soft tissue tumors of the skin. Markers such as alpha-smooth muscle actin (alpha-SMA) and desmin, considered specific for smooth muscle cell (SMC), have been shown to be expressed in a variety of fibroblastic and myofibroblastic processes. High-molecular-weight caldesmon (h-caldesmon), one of two isoforms, is reported to be expressed exclusively by SMC and has recently been shown to be a specific marker of SMC tumors.
METHODS: Tumors were obtained from 11 patients taken from the surgical pathology archives of the University of South Florida and cases were coded as smooth muscle hamartoma, myofibroma, and dermatomyofibroma.
RESULTS: The case of smooth muscle hamartoma had greater than 90% of tumor cells labeling with anti-h-caldesmon antibodies. Three of three cases of myofibroma had focal areas of positivity representing less than 10% of total tumor cells. Seven of seven dermatomyofibromas showed no apparent labeling with anti-h-caldesmon antibody. Dense reactivity was noted in vascular wall smooth muscle, indicating internal controls.
CONCLUSIONS: We can conclude that h-caldesmon is a specific marker of fully differentiated smooth muscle and that it can serve to differentiate spindled SMC soft tissue tumors of the skin from tumors of myofibroblastic and/or fibroblastic origin.
PROGNOSIS AND TREATMENT CHARACTERIZATION Treatment Excision Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
Smooth muscle actin-These are specific for smooth muscle. Antibodies directed against these intermediate filaments can be used to confirm the identity of this tumor.
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