Cellular angiofibroma

Last updated
Cellular angiofibroma
Specialty Gynecology, Urology, Dermatology, Pathology, General surgery
Symptoms Growth of a painless, soft tissue tumor in vulva-vaginal, inguinal-scrotal, or other areas
Complications Extremely rare recurrence after surgical removal
Usual onsetAdults >30 years old
Types Benign tumor
CausesUnknown
Treatment Surgical resection
Prognosis Excellent
FrequencyRare
DeathsNone

Cellular angiofibroma (CAF) is a rare, benign tumor of superficial soft tissues that was first described by M. R. Nucci et al. in 1997. [1] These tumors occur predominantly in the distal parts of the female and male reproductive systems, i.e. in the vulva-vaginal and inguinal-scrotal areas, respectively, or, less commonly, in various other superficial soft tissue areas throughout the body. [2] CAF tumors develop exclusively in adults who typically are more than 30 years old. [3]

Contents

CAF tumors are composed of bland mesenchymal [4] spindle-shaped cells in an edematous (i.e. abnormally swollen with fluid) to fiber-laded connective tissue background. [2] Mesenchymal cells are cells in the cell lineage that includes fibroblasts, adipocytes (i.e. fat cells), macrophages, mast cells, leucocytes, and the precursor cells which mature into these cell types. In 2020, the World Health Organization classified cellular angiofibroma tumors in the category of benign fibroblastic and myofibroblastic tumors. [5]

CAF tumors rarely recur after surgical removal [3] and do not metastasize to distant tissues. [5] Accordingly, surgical resection is the commonly performed and current standard for treating these tumors. [6]

Presentation

CAF tumors commonly present as painless, slowly growing, soft tissue nodules or masses in the vulva-vaginal and inguinal-scrotal areas; less commonly in the perineum; and rarely in the urethra, pelvis, anus, retroperitoneum, lumbar region, middle of the trunk, [7] rectum, oral mucosa, knee, upper eyelid, [6] hip, chest wall, axilla, breasts, and upper abdomen. [2] The tumors are generally centered in the subcutaneous tissue [4] or in the case of internal tumors, such as those located in the mouth, urethra, rectum, or anus, the submucosa. [6] In one study of 51 individuals, these tumors had been noticed for 1 week to 5 years (median time: 5 months) prior to diagnosis in women (median age: 47 years) and men (median age: 60 years). Their tumors ranged from 0.6 to 25.0 cm in maximum diameter size (median size 2.7 cm in women and 6.7 cm in men). [7]

Pathology

Grossly, CAF tumors appear as well-circumscribed, firm to rubbery, white/tan to grayish masses some of which appear to consist of multiple lobules. [7] Rarely, these tumors had infiltrated into adjacent muscles or other nearby tissues. [3] As determined by microscopic analyses, CAF tumors are composed of bland spindle-shaped cells in an edematous to fibrous stromal background containing bundles of collagen fibers, small to medium-sized, thick-walled, prominently hyalinized (i.e. glassy appearing) blood vessels, and a minor component of adipose tissue (i.e. fat tissue). Numerous mast cells, moderate numbers of lymphocytes, and small numbers of neutrophils are scattered throughout this stroma; this stroma does not contain the multinucleated giant cells or epithelioid cells that are often found in certain other types of mesenchymal tumors. [2] However, CAF lesions may contain scattered, abnormally-shaped cells, lipoblasts (i.e. immature fat cells), and diffuse malignant-appearing sarcoma-like changes but these findings do not alter the prognosis of CAF as being a purely benign tumor. [3]

Immunohistochemical analyses find that the cells in CAF tumors express the CD34 protein in ~50% of cases, a smooth muscle actin protein in occasional cases, MUC1 (also termed EMA) and desmin proteins in a minority of cases, but do not express S100 or cytokeratin proteins. [3] [4] [6] Most cases of CAF in females contain CAF tumor cells which express estrogen and progesterone receptors [4] while limited studies in males reported that 3 of 3 CAF cases contained estrogen receptor-expressing tumor cells while only 1 of 3 cases contained progesterone receptor-expressing tumor cells. [8] Detection of one or more of these protein expression patterns can help differentiate CAF from other types of mesenchymal tumors. [3] [4] [6]

Chromosome and gene abnormalities

Fluorescence in situ hybridization analysis shows that the neoplastic cells in all cases of CAF have a deletion in or around band 14 on the long (or "q") arm of one of their two chromosomes 13. This results in a loss of one of the two RB1 genes (located at band 14.2 on the q arm of this chromosome [9] ) as well as one of the two FOXO1 genes (located at band 14.11 on the q arm of this chromosome [10] ). [4] [11] Deletion of one of the RB1 genes, it is proposed but not yet demonstrated, may act to promote the development and/or progression of CAF tumors. In any event, loss of this gene in one of the two chromosome 13s is extremely helpful for distinguishing CAF from most other mesenchymal tumor types. [4]

Diagnosis

The diagnosis of CAF generally depends on its typical location in vulva-vaginal and inguinal-scrotal areas, spindle-shaped cell histopathology, tumor cell expressions of marker proteins, and absence of one of the two RP1 genes. CAF can be hard to distinguish from two other spindle-shaped cell tumors, myofibroblastoma and spindle cell lipoma, that commonly also contain tumors cells with deletions in one of their two RF1 genes. The characteristic hyalinized blood vessels and the presence of CD34 protein-expressing and desmin protein-expressing cells in CAF help to distinguish it from myofibroblastoma. [3] Unlike CAF, spindle cell lipomas seldom contain desmin protein-expressing or progesterone receptor-expressing tumor cells [3] and commonly contain CD99- and S100-expressing proteins. [6] In addition, spindle cell lipomas are rare in the vulvovaginal region and their tumor vasculature consists of capillary-sized, thin-walled blood vessels while those of CAF consist of more numerous blood vessels with thick, hyalinized walls. [2] CAR and angiomyofibroblastoma can be difficult to distinguish from one another but angiomyofibroblastoma tumor cells show no alterations in their RB1 and FOXO1 genes. [12]

Treatment and prognosis

The current standard for treating CAF tumors is total surgical resection (i.e. resection that does not leave any residual neoplastic tissue behind). [6] This treatment appears adequate (i.e. curative) even in cases were CAF tumors contain atypical cells and/or sarcoma-like histopathology. [2] In many reported cases, CAF tumors treated with simple surgical excision or “shelling out” also appeared to have achieved adequate results. [4] CAF tumors rarely recur at the sites of their surgical removal whether treated by total or simple resections [3] and have not been reported to metastasize. Consequently, the prognosis for CAF is excellent. [2] [4]

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A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize. Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.

<span class="mw-page-title-main">Liposarcoma</span> Medical condition

Liposarcomas are the most common subtype of soft tissue sarcomas, accounting for at least 20% of all sarcomas in adults. Soft tissue sarcomas are rare neoplasms with over 150 different histological subtypes or forms. Liposarcomas arise from the precursor lipoblasts of the adipocytes in adipose tissues. Adipose tissues are distributed throughout the body, including such sites as the deep and more superficial layers of subcutaneous tissues as well as in less surgically accessible sites like the retroperitoneum and visceral fat inside the abdominal cavity.

<span class="mw-page-title-main">Nodular fasciitis</span> Medical condition

Nodular fasciitis (NF) is a benign, soft tissue tumor composed of myofibroblasts that typically occurs in subcutaneous tissue, fascia, and/or muscles. The literature sometimes titles rare NF variants according to their tissue locations. The most frequently used and important of these are cranial fasciitis and intravascular fasciitis. In 2020, the World Health Organization classified nodular fasciitis as in the category of benign fibroblastic/myofibroblastic tumors. NF is the most common of the benign fibroblastic proliferative tumors of soft tissue.

<span class="mw-page-title-main">Undifferentiated pleomorphic sarcoma</span> Medical condition

Undifferentiated pleomorphic sarcoma (UPS), also termed pleomorphic myofibrosarcoma, high-grade myofibroblastic sarcoma, and high-grade myofibrosarcoma, is characterized by the World Health Organization (WHO), 2020, as a rare, poorly differentiated neoplasm, i.e. an abnormal growth of cells that have an unclear identity and/or cell of origin. WHO classified it as one of the undifferentiated/unclassified sarcomas in the category of tumors of uncertain differentiation. Sarcomas are cancers known or thought to derive from mesenchymal stem cells that typically develop in bone, muscle, fat, blood vessels, lymphatic vessels, tendons, and ligaments. More than 70 sarcoma subtypes have been described. The UPS subtype of these sarcomas consists of tumor cells that are poorly differentiated and may appear as spindle-shaped cells, histiocytes, and giant cells. UPS is considered a diagnosis that defies formal sub-classification after thorough histologic, immunohistochemical, and ultrastructural examinations fail to identify the type of cells involved.

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<span class="mw-page-title-main">Angiofibroma</span> Medical condition

Angiofibroma (AGF) is a descriptive term for a wide range of benign skin or mucous membrane lesions in which individuals have:

  1. benign papules, i.e. pinhead-sized elevations that lack visible evidence of containing fluid;
  2. nodules, i.e. small firm lumps usually >0.1 cm in diameter; and/or
  3. tumors, i.e. masses often regarded as ~0.8 cm or larger.
<span class="mw-page-title-main">Aggressive angiomyxoma</span> Medical condition

Angiomyxoma is a myxoid tumor involving the blood vessels.

Infantile digital fibromatosis (IDF), also termed inclusion body fibromatosis, Reye tumor, or Reye's tumor, usually occurs as a single, small, asymptomatic, nodule in the dermis on a finger or toe of infants and young children. IMF is a rare disorder with approximately 200 cases reported in the medical literature as of 2021. The World Health Organization in 2020 classified these nodules as a specific benign tumor type in the category of fibroblastic and myofibroblastic tumors. IDF was first described by the Australian pathologist, Douglas Reye, in 1965.

Fibrous hamartoma of infancy (FHI) is a rare, typically painless, benign tumor that develops in the subcutaneous tissues of the axilla, arms, external genitalia, or, less commonly, various other areas. It is diagnosed in children who are usually less than 2 years old or, in up to 20% of cases, develops in utero and is diagnosed in an infant at birth.

<span class="mw-page-title-main">Koenen's tumor</span> Medical condition

Koenen's tumor (KT), also commonly termed periungual angiofibroma, is a subtype of the angiofibromas. Angiofibromas are benign papule, nodule, and/or tumor lesions that are separated into various subtypes based primarily on the characteristic locations of their lesions. KTs are angiofibromas that develop in and under the toenails and/or fingernails. KTs were once considered as the same as another subtype of the angiofibromas viz., acral angiofibromas. While the literature may still sometimes regard KTs as acral angiofibromas, acral angiofibromas are characteristically located in areas close to but not in the toenails and fingernails as well as in the soles of the feet and palms of the hands. KTs are here regarded as distinct from acral angiofibromas.

<span class="mw-page-title-main">Low-grade fibromyxoid sarcoma</span> Medical condition

Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of low-grade sarcoma first described by H. L. Evans in 1987. LGFMS are soft tissue tumors of the mesenchyme-derived connective tissues; on microscopic examination, they are found to be composed of spindle-shaped cells that resemble fibroblasts. These fibroblastic, spindle-shaped cells are neoplastic cells that in most cases of LGFMS express fusion genes, i.e. genes composed of parts of two different genes that form as a result of mutations. The World Health Organization (2020) classified LGFMS as a specific type of tumor in the category of malignant fibroblastic and myofibroblastic tumors.

<span class="mw-page-title-main">Mammary-type myofibroblastoma</span> Medical condition

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Vulvar tumors are those neoplasms of the vulva. Vulvar and vaginal neoplasms make up a small percentage (3%) of female genital cancers. They can be benign or malignant. Vulvar neoplasms are divided into cystic or solid lesions and other mixed types. Vulvar cancers are those malignant neoplasms that originate from vulvar epithelium, while vulvar sarcomas develop from non-epithelial cells such as bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Epithelial and mesenchymal tissue are the origin of vulvar tumors.

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<span class="mw-page-title-main">Proliferative fasciitis and proliferative myositis</span> Medical condition

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Angiofibroma of soft tissue (AFST), also termed angiofibroma, not otherwise specified, is a recently recognized and rare disorder that was classified in the category of benign fibroblastic and myofibroblastic tumors by the World Health Organization in 2020. An AFST tumor is a neoplasm that was first described by A. Mariño-Enríquez and C.D. Fletcher in 2012.

Gardner fibroma (GF) is a benign fibroblastic tumor. GF tumors typically develop in the dermis and adjacent subcutaneous tissue lying just below the dermis. These tumors typically occur on the back, abdomen, and other superficial sites but in rare cases have been diagnoses in internal sites such as the retroperitoneum and around the large blood vessels in the upper thoracic cavity. The World Health Organization, 2020, classified Gardner fibroma as a benign tumor in the category of fibroblastic and myofibroblastic tumors.

References

  1. ↑ Nucci MR, Granter SR, Fletcher CD (June 1997). "Cellular angiofibroma: a benign neoplasm distinct from angiomyofibroblastoma and spindle cell lipoma". The American Journal of Surgical Pathology. 21 (6): 636–44. doi:10.1097/00000478-199706000-00002. PMID   9199640.
  2. 1 2 3 4 5 6 7 Mandato VD, Santagni S, Cavazza A, Aguzzoli L, Abrate M, La Sala GB (July 2015). "Cellular angiofibroma in women: a review of the literature". Diagnostic Pathology. 10: 114. doi: 10.1186/s13000-015-0361-6 . PMC   4506619 . PMID   26187500.
  3. 1 2 3 4 5 6 7 8 9 Libbrecht S, Van Dorpe J, Creytens D (March 2021). "The Rapidly Expanding Group of RB1-Deleted Soft Tissue Tumors: An Updated Review". Diagnostics (Basel, Switzerland). 11 (3): 430. doi: 10.3390/diagnostics11030430 . PMC   8000249 . PMID   33802620.
  4. 1 2 3 4 5 6 7 8 9 Chapel DB, Cipriani NA, Bennett JA (January 2021). "Mesenchymal lesions of the vulva". Seminars in Diagnostic Pathology. 38 (1): 85–98. doi:10.1053/j.semdp.2020.09.003. PMID   32958293. S2CID   221842800.
  5. 1 2 Sbaraglia M, Bellan E, Dei Tos AP (April 2021). "The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives". Pathologica. 113 (2): 70–84. doi:10.32074/1591-951X-213. PMC   8167394 . PMID   33179614.
  6. 1 2 3 4 5 6 7 Bloom J, Jordan E, Baratta VM, Zhang X, Saha A, Yavorek G, Kurbatov V (November 2020). "Cellular Angiofibroma Presenting as a Subepithelial Rectal Mass". ACG Case Reports Journal. 7 (11): e00471. doi:10.14309/crj.0000000000000471. PMC   7678802 . PMID   33235884.
  7. 1 2 3 Iwasa Y, Fletcher CD (November 2004). "Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases". The American Journal of Surgical Pathology. 28 (11): 1426–35. doi:10.1097/01.pas.0000138002.46650.95. PMID   15489646. S2CID   44943734.
  8. ↑ Sugita S, Aoyama T, Kondo K, Keira Y, Ogino J, Nakanishi K, Kaya M, Emori M, Tsukahara T, Nakajima H, Takagi M, Hasegawa T (August 2014). "Diagnostic utility of NCOA2 fluorescence in situ hybridization and Stat6 immunohistochemistry staining for soft tissue angiofibroma and morphologically similar fibrovascular tumors". Human Pathology. 45 (8): 1588–96. doi:10.1016/j.humpath.2013.12.022. PMID   24856853.
  9. ↑ "RB1 RB transcriptional corepressor 1 [Homo sapiens (Human)] - Gene – NCBI".
  10. ↑ "FOXO1 forkhead box O1 [Homo sapiens (Human)] - Gene – NCBI".
  11. ↑ Chen BJ, Mariño-Enríquez A, Fletcher CD, Hornick JL (August 2012). "Loss of retinoblastoma protein expression in spindle cell/pleomorphic lipomas and cytogenetically related tumors: an immunohistochemical study with diagnostic implications". The American Journal of Surgical Pathology. 36 (8): 1119–28. doi:10.1097/PAS.0b013e31825d532d. PMID   22790852. S2CID   24256957.
  12. ↑ Calvert H, Kapurubandara S, Nikam Y, Sharma R, Achan A (2018). "A Vaginal Angiomyofibroblastoma as a Rare Cause of a Prolapsing Vaginal Mass: A Case Report and Review of the Literature". Case Reports in Obstetrics and Gynecology. 2018: 8579026. doi: 10.1155/2018/8579026 . PMC   5949183 . PMID   29854515.
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