Hubbry Logo
Sarcoma botryoidesSarcoma botryoidesMain
Open search
Sarcoma botryoides
Community hub
Sarcoma botryoides
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Sarcoma botryoides
Sarcoma botryoides
Sarcoma botryoides
View on Wikipedia
from Wikipedia
Sarcoma botryoides
Other namesBotryoid rhabdomyosarcoma
SpecialtyOncology

Sarcoma botryoides or botryoid sarcoma[1] is a subtype of embryonal rhabdomyosarcoma, that can be observed in the walls of hollow, mucosa lined structures such as the nasopharynx, common bile duct, urinary bladder of infants and young children or the vagina in females, typically younger than age 8. The name comes from Ancient Greek botryoid 'grape bunch' due to their gross appearance.

Presentation

[edit]

For botryoid rhabdomyosarcoma of the vagina, the most common clinical finding is vaginal bleeding[2] but vaginal bleeding is not specific for sarcoma botryoides: other vaginal cancers are possible. They may appear as a polypoid mass, somewhat yellow in color and are friable: thus, they (possibly) may break off, leading to vaginal bleeding or infections.[citation needed]

Histology

[edit]

Under the microscope one can see rhabdomyoblasts that may contain cross-striations. Tumor cells are crowded in a distinct layer beneath the vaginal epithelium (cambium layer). Spindle-shaped tumor cells that are desmin positive.[citation needed]

Treatment

[edit]

The disease used to be uniformly fatal, with a 5-year survival rate between 10 and 35%.[3] As a result, treatment was radical surgery. New multidrug chemotherapy regimens with or without radiation therapy are now used in combination with less radical surgery with good results, although outcome data are not yet available.[4]

Epidemiology

[edit]

Sarcoma botryoides normally is found in children under 8 years of age. Onset of symptoms occurs at age 3 years (38.3 months) on average.[5] Cases of older women with this condition have also been reported.[6]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Sarcoma botryoides

View on Grokipedia
from Grokipedia
Sarcoma botryoides, also known as botryoid , is a rare and aggressive subtype of originating from immature cells called rhabdomyoblasts, distinguished by its characteristic grape-like (from the Greek botrys, meaning "bunch of grapes") polypoid masses that protrude into hollow organs. It most commonly affects the genitourinary tract, particularly the vagina and in young females, but can also occur in sites such as the , , nasopharynx, and . This malignancy predominantly impacts children under the age of 4 years, with an annual incidence of fewer than 4 cases per million children, accounting for 5-10% of cases. It is more frequent in females due to its predilection for the genital tract, though rare cases have been reported in males and older adolescents or adults. Rare familial occurrences suggest potential genetic predispositions, such as Li-Fraumeni syndrome. Clinical presentation often includes abnormal , a visible protruding mass, or discharge, which can lead to early detection in pediatric patients but may mimic benign conditions like polyps. Diagnosis relies on a combination of clinical evaluation, imaging modalities such as and MRI to assess tumor extent, and histopathological confirmation through , which reveals rhabdomyoblastic cells in an edematous stroma, sometimes with a characteristic "cambium layer" of subepithelial tumor cells. , positive for markers like desmin and myogenin, further supports the , while staging follows systems like the Intergroup (IRSG) criteria or TNM classification to guide therapy. Treatment has evolved from to multimodal approaches emphasizing fertility preservation, typically involving initial surgical (e.g., polypectomy or ), followed by multi-agent regimens such as , actinomycin D, and (VAC), with reserved for relapsed or unresectable cases. Advances from IRSG trials have significantly reduced the need for extensive , dropping from 100% in early studies to about 13% in later ones. Prognosis is generally favorable compared to other rhabdomyosarcoma subtypes, with 5-year survival rates exceeding 95% for early-stage, nonmetastatic disease, though recurrence occurs in 45-73% of cases and is influenced by factors such as tumor stage and histology.

Definition and Classification

Definition

Sarcoma botryoides, also known as botryoid embryonal rhabdomyosarcoma, is a rare and aggressive variant of embryonal rhabdomyosarcoma arising from immature skeletal muscle precursor cells known as rhabdomyoblasts. This malignant tumor develops from undifferentiated mesenchymal tissue that exhibits primitive features of skeletal muscle differentiation. The tumor is distinguished by its macroscopic appearance as a grape-like (botryoid) polypoid mass, featuring fleshy, nodular projections that protrude into the lumen of affected hollow organs. This structure often displays a translucent, edematous, and myxoid quality, resembling a cluster of grapes due to its multicystic and bulging form. Sarcoma botryoides predominantly involves the mucosal surfaces of hollow organs in the genitourinary and biliary tracts. It typically arises beneath the epithelial lining, forming expansive growths that disrupt normal organ function.

Classification Within

Sarcoma botryoides, also known as botryoid , is a polypoid variant of (ERMS), the most common histological subtype of rhabdomyosarcoma in children, comprising approximately 70%–75% of all cases. This variant accounts for about 10% of all pediatric rhabdomyosarcomas and is characterized by its occurrence beneath mucosal surfaces, such as in the , , or . Unlike typical ERMS, the botryoid form exhibits a distinctive subepithelial layer of densely packed rhabdomyoblasts, which aids in its pathological identification. In the 2020 World Health Organization (WHO) Classification of Soft Tissue Tumours, rhabdomyosarcoma is divided into four main histological subtypes: embryonal, alveolar, spindle cell/sclerosing, and pleomorphic, with the botryoid variant included under embryonal rhabdomyosarcoma. Botryoid rhabdomyosarcoma is distinguished from other rhabdomyosarcoma subtypes, particularly the alveolar variant, which represents 20%–25% of cases and typically affects older children or adolescents. Alveolar rhabdomyosarcoma is defined by the presence of ::FOXO1 or PAX7::FOXO1 gene fusions in roughly 80% of instances, conferring a more aggressive clinical course and poorer . In contrast, botryoid cases, like most ERMS, are fusion-negative, lacking these characteristic translocations and instead showing genetic alterations such as RAS pathway mutations or copy number losses at 11p15.5. The pleomorphic subtype, rare in pediatric populations and primarily seen in adults, features large, pleomorphic cells with a high mitotic rate and is associated with unfavorable outcomes, further differentiating it from the younger age of onset (typically under 5 years) and mucosal predilection of botryoid ERMS. In the International Classification of (ICR), established by the Intergroup Rhabdomyosarcoma Study Group, botryoid rhabdomyosarcoma is grouped with spindle cell/sclerosing ERMS as a superior-risk (favorable ) category when localized, contrasting with the intermediate-risk designation for typical ERMS and the superior-risk (unfavorable) status for alveolar and undifferentiated types. This emphasizes its better event-free survival rates—around 80% in Children's Oncology Group studies—compared to fusion-positive alveolar cases, guiding risk-adapted therapeutic approaches.

Epidemiology

Incidence and Demographics

Sarcoma botryoides, a rare variant of , has an estimated annual incidence of approximately 0.5 cases per million children under 20 years, based on comprising about 10% of all cases. This subtype accounts for approximately 10% of all cases, which themselves represent about 50% of childhood sarcomas, positioning sarcoma botryoides as roughly 5% of the broader category of pediatric sarcomas. The disease exhibits a strong female predominance, with over 90% of cases occurring in females, primarily due to its frequent involvement of the genital tract such as the and . Age distribution peaks in , with the majority of diagnoses in children under 5 years and the highest incidence in infants under 2 years old; the median age at presentation for genital tract cases is approximately 2.9 years. While exceedingly rare in adults, sarcoma botryoides has been documented in women of reproductive age, particularly in association with cervical or uterine involvement, where the median age at can extend to around 18 years in mixed pediatric-adult cohorts.

Associated Risk Factors

Sarcoma botryoides, a variant of (ERMS), is primarily a sporadic condition with no well-established environmental risk factors or triggers identified in the literature. Unlike some adult cancers, there is no consistent evidence linking viral infections, such as human papillomavirus, or prior specifically to the development of the botryoid subtype. Rare associations exist between sarcoma botryoides and congenital anomalies, particularly urogenital malformations that may predispose to tumor formation in mucosal-lined structures like the or . These include structural defects such as vaginal septa or other genitourinary tract abnormalities, though such cases represent a small minority and do not imply direct causation. High birth weight or large size for has also been noted as a potential for ERMS in general, potentially overlapping with botryoid presentations. Genetic predispositions play a role in a subset of cases, with mutations increasing susceptibility to ERMS variants including botryoid. Li-Fraumeni syndrome, characterized by TP53 mutations, is associated with approximately 1.7% of cases and elevates risk for multiple sarcomas. Beckwith-Wiedemann syndrome, involving 11p15 imprinting defects and overgrowth features, similarly heightens the likelihood of developing ERMS. For the botryoid subtype, particularly in uterine or cervical sites, DICER1 syndrome is a notable genetic link, with pathogenic variants identified in a significant proportion of genitourinary ERMS tumors. These syndromes collectively account for 6%–8% of predispositions, underscoring a hereditary component in otherwise sporadic disease. The condition predominantly affects young females, aligning with its common sites in the female genital tract.

Clinical Presentation

Signs and Symptoms

Sarcoma botryoides, a variant of , most commonly presents with or bloody discharge as the initial symptom, which is often painless in the early stages. This bleeding typically occurs in pediatric patients, particularly young girls, and may be accompanied by or spotting. A characteristic feature is the protrusion of a soft, grape-like polypoid mass from the l introitus, which can be visible externally and is often described as having a nodular, botryoid ( cluster) appearance. In cases involving the vagina, patients may also experience foul-smelling discharge due to secondary of the protruding lesion. When the tumor affects other sites such as the , symptoms can include urinary obstruction or , leading to discomfort or incontinence. Involvement of the may manifest as obstructive and abdominal distention, occasionally with or fever. For nasopharyngeal involvement, symptoms often include nasal obstruction, epistaxis, and .

Common Anatomical Sites

Sarcoma botryoides, a variant of , most frequently arises in the , where it accounts for approximately half of all cases and presents as a polypoid, grape-like mass with submucosal growth beneath the intact . This site is particularly common in infants and young girls under 5 years of age. Other genital tract locations include the , which is more typical in adolescent and females, and the . Extragenital sites occur less commonly and encompass the , common bile ducts, and nasopharynx. The tumor is exclusively associated with hollow, mucosa-lined organs, enabling its characteristic botryoid growth pattern that expands beneath the mucosal surface.

Pathophysiology

Etiology

Sarcoma botryoides, a variant of (ERMS), arises from primitive mesenchymal cells that fail to differentiate into mature tissue. This developmental arrest involves myogenic regulatory factors, including MYOD1 and myogenin, which are transcription factors essential for differentiation but aberrantly expressed in these tumors, contributing to the immature phenotype. Key genetic alterations in sarcoma botryoides include (LOH) at 11p15, observed in approximately 50% of ERMS cases, which affects the IGF2/H19 locus and leads to biallelic IGF2 expression, contributing to tumor initiation. Additionally, mutations in the RAS pathway, such as in NRAS (11.7%), (6.4%), and (4.3%), occur frequently and activate downstream signaling to sustain cell growth. Unlike , sarcoma botryoides lacks characteristic FOXO1 fusions (e.g., PAX3-FOXO1 or PAX7-FOXO1), aligning it molecularly with the fusion-negative subset of ERMS. The tumor's distinctive botryoid morphology is influenced by its origin in mucosal-lined hollow viscera, where the submucosal location and interaction with overlying promote polypoid, grape-like expansion rather than deeply invasive growth. In rare cases, sarcoma botryoides is associated with Li-Fraumeni syndrome due to germline TP53 mutations, which predispose to ERMS development.

Histological Features

Sarcoma botryoides, a variant of , exhibits distinctive microscopic features that facilitate its pathological . The hallmark is the cambium layer, a hypercellular condensation of primitive tumor cells immediately subjacent to the intact mucosal , creating a dense, subepithelial band that resembles embryonic . This layer consists of undifferentiated round or spindled cells with scant and frequent mitotic figures, contrasting with the looser deeper tumor components. The tumor is composed of rhabdomyoblastic cells, including strap-like forms with abundant cytoplasm and tadpole-shaped cells featuring elongated cytoplasmic tails; cross-striations may be visible in these differentiating elements, particularly after . Interspersed within a loose myxoid stroma are spindle-shaped cells and perivascular condensations of tumor cells, contributing to the overall paucicellular appearance in deeper regions. Immunohistochemical staining confirms the myogenic differentiation, with diffuse positivity for desmin and nuclear positivity for myogenin and MYOD1 (often scattered) in the tumor cells; these markers help distinguish sarcoma botryoides from other small round blue cell tumors.

Diagnosis

Clinical Assessment

The clinical assessment of suspected sarcoma botryoides begins with a detailed history-taking, focusing on symptoms commonly reported in young females, typically under 5 years of age or during . Patients often present with abnormal , which may be the initial complaint, alongside vaginal discharge that can be leukorrheic or malodorous, or a noticeable protrusion of a mass from the vaginal introitus. These symptoms, such as , align with the broader clinical presentation outlined in . A family history should be elicited, as rare cases of familial occurrence have been documented, including reports of affected sisters suggesting possible in select instances. Physical examination is crucial and often reveals a characteristic polypoid, vascular mass protruding at the vaginal introitus, resembling a cluster of grapes (botryoid appearance) due to its nodular and features. The mass is typically non-tender but may show signs of and vascularity, with no extension beyond the visible area in early presentations; should be gentle to avoid trauma. In adolescent cases, the may involve the , presenting as a protruding polyp without parametrial involvement on initial exam. Differential diagnosis must consider benign conditions mimicking these findings, such as vaginal or cervical polyps, which are uncommon in children and warrant exclusion to prevent misdiagnosis. Infectious causes, including or reactions, should also be evaluated, particularly if discharge predominates. Other sarcomas or mesenchymal tumors, like adenosarcoma or , enter the consideration, as do fibroepithelial stromal polyps (formerly known as pseudosarcoma botryoides), which lack malignant features on .

Imaging and Pathological Confirmation

Imaging plays a crucial role in the and staging of sarcoma botryoides, a variant of (ERMS), by delineating the tumor's extent and assessing for . serves as the initial modality, particularly for pelvic evaluation in genitourinary sites, revealing a well-defined, hypoechoic, inhomogeneous mass with increased vascular flow. (MRI) is preferred for delineation, demonstrating the characteristic polypoid, grape-like mass with myxoid stroma appearing as T2 hyperintensity and diffusion restriction on advanced sequences, while also evaluating local invasion and regional lymph nodes. Computed (CT) is utilized for assessment, including chest for pulmonary involvement and abdominal/pelvic scans to identify nodal or distant spread. Pathological confirmation requires , typically performed under as an incisional or excisional procedure to obtain adequate tissue while minimizing risk in pediatric patients. For vaginal or cervical lesions, a vulvar or transvaginal approach is common, often guided by or for involvement. Histological examination reveals the diagnostic layer of loosely arranged tumor cells beneath the mucosa, with confirming ERMS through positivity for markers such as desmin and myogenin. Molecular analysis may assess for fusion status, though botryoid ERMS is typically FOXO1 fusion-negative. Staging follows the Intergroup Rhabdomyosarcoma Study Group (IRSG) system, which integrates clinical and surgical-pathologic findings to categorize disease from Group I (completely resected, localized) to Group IV (distant metastases). Sites such as the or are classified as Stage I (favorable, confined to the organ of origin without nodal or distant involvement), often falling into Group III if gross residual disease remains after or partial resection. This staging informs risk stratification and treatment planning.

Treatment

Surgical Interventions

Surgical interventions form the cornerstone of treatment for sarcoma botryoides, a rare variant of primarily affecting the female genital tract in young patients, with approaches evolving from historically aggressive procedures to more conservative, fertility-preserving strategies when feasible. Early management prioritizes complete tumor resection while minimizing functional and cosmetic impairment, particularly in pediatric and adolescent cases where organ preservation is critical. For localized vaginal disease, fertility-sparing techniques such as polypectomy or partial are preferred to achieve negative margins without compromising reproductive potential. Polypectomy involves excision of the polypoid tumor mass protruding from the vaginal or , as demonstrated in cases of cervical involvement where it successfully removed tumors measuring up to 5 cm while preserving . Partial targets superficial lesions confined to the vaginal wall, allowing for in infants and young children, with reported application in patients as young as 11 months. These procedures are selected for early-stage tumors (e.g., IRSG Group I or II) to facilitate subsequent without the need for more invasive surgery. In advanced, recurrent, or persistent cases, more radical options such as or may be necessary to ensure complete resection. Total abdominal , often combined with salpingo-oophorectomy, is reserved for tumors extending into the uterine corpus or failing initial conservative management, as seen in cases post-neoadjuvant therapy. , involving removal of pelvic organs including the and , is now rarely performed upfront but considered for refractory disease to achieve local control. Debulking surgery plays a key role in symptom relief for bulky, obstructive tumors, reducing and hemorrhage prior to further treatment. Within a multimodal framework, interventions are often sequenced after initial to shrink tumor bulk, enabling less radical excisions and improving resectability. This neoadjuvant approach, followed by delayed primary , has become standard for optimizing outcomes while integrating with systemic therapies.

Chemotherapy and Radiation Therapy

forms a cornerstone of treatment for sarcoma botryoides, a botryoid variant of , typically administered as multi-agent regimens to address both localized and potential microscopic disease. The standard approach involves the , actinomycin D, and (VAC) regimen, delivered over 6 to 12 cycles depending on risk stratification and tumor response. Neoadjuvant is employed to shrink the tumor prior to intervention, facilitating more conservative resection, while adjuvant cycles target residual microscopic disease post-. This protocol has been established through cooperative group trials, demonstrating efficacy in improving local control without excessive toxicity in pediatric patients. Radiation therapy is generally avoided in young children with sarcoma botryoides due to the high risk of long-term morbidity, including and secondary malignancies, particularly in genital tract sites. It is reserved for cases of unresectable , incomplete resection with gross residual tumor, or recurrence, with doses typically ranging from 40 to 50.4 Gy delivered via external beam or . , using vaginal cylinders, is particularly suitable for vaginal primaries to precisely target the tumor while sparing surrounding tissues and preserving organ function. Intensity-modulated techniques may further reduce exposure to adjacent structures in select cases. For relapsed or refractory sarcoma botryoides, emerging targeted therapies are being explored, particularly anti-angiogenic agents that exploit the tumor's prominent vascular histology. Agents such as have been investigated in phase II trials for relapsed high-risk , with mixed results regarding efficacy in improving event-free survival. These approaches are often integrated into multimodal salvage regimens, though their role remains investigational pending further validation in prospective studies.

Prognosis

Survival Outcomes

Sarcoma botryoides, a subtype of (ERMS), exhibits favorable outcomes, particularly for localized disease, with a 5-year overall of 95% in non-metastatic cases treated with multidisciplinary approaches including , , and . For non-localized disease, 5-year rates vary by clinical group and extent of disease, ranging from approximately 70% for group II to 25% for metastatic group IV. Despite these encouraging figures, sarcoma botryoides has a high recurrence rate of 45-73%, with most relapses occurring within 2 years of initial treatment, often in the or lungs. However, salvage for recurrent botryoid ERMS achieves a 5-year post-relapse of 64%, significantly higher than the 26% observed in other embryonal RMS subtypes. Overall, survival outcomes for sarcoma botryoides are improved compared to non-botryoid ERMS due to its favorable histological features and typical presentation in accessible sites like the or , allowing for earlier detection and intervention.

Factors Influencing Prognosis

Several factors influence the prognosis of sarcoma botryoides, a botryoid variant of , with outcomes varying based on patient demographics, tumor characteristics, and treatment response. Favorable prognostic factors include younger age at , particularly under 10 years, which is associated with improved event-free and overall rates compared to older children. A primary site in the also correlates with excellent outcomes, often achieving near-complete in localized cases due to the tumor's superficial and for intervention. Additionally, IRSG Stage I , characterized by localized tumors without regional spread, and complete surgical resection (Group I) significantly enhance long-term by allowing definitive local control. Adverse factors that worsen encompass the presence of metastases at , which shifts cases to Stage IV and drastically reduces survival probabilities through widespread dissemination. An incomplete response to further compromises outcomes by hindering tumor regression and increasing the risk of persistent disease. Moreover, recurrence within the first year post-treatment indicates aggressive biology and is linked to poorer salvage rates compared to later relapses. The genetic profile plays a critical role, with TP53 mutations particularly detrimental in syndromic cases such as Li-Fraumeni syndrome, where they contribute to treatment resistance and reduced event-free survival. In contrast, the absence of PAX/FOXO1 gene fusions, common in embryonal subtypes like botryoid, is associated with a more favorable prognosis.

References

  1. https://www.osmosis.org/answers/sarcoma-botryoides
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC10000398/
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3026308/
  4. https://www.pathologyoutlines.com/topic/softtissueembryonalrhabdo.html
  5. https://www.cancer.gov/types/soft-tissue-sarcoma/hp/rhabdomyosarcoma-treatment-pdq
  6. https://pmc.ncbi.nlm.nih.gov/articles/PMC6071337/
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC4651658/
  8. https://hjog.org/?p=2854
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC3939703/
  10. https://www.cancer.org/cancer/types/rhabdomyosarcoma/causes-risks-prevention.html
  11. https://www.mountsinai.org/health-library/diseases-conditions/rhabdomyosarcoma
  12. https://siope.eu/media/documents/escp-rhabdomyosarcoma.pdf
  13. https://pmc.ncbi.nlm.nih.gov/articles/PMC5406612/
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC6629268/
  15. https://www.cancer.org/cancer/types/rhabdomyosarcoma/detection-diagnosis-staging/signs-symptoms.html
  16. http://journalononcology.org/pdf/1033.pdf
  17. https://doi.org/10.1097/PAP.0b013e3182a92d0d
  18. https://pubmed.ncbi.nlm.nih.gov/10666368/
  19. https://doi.org/10.1158/2159-8290.CD-13-0639
  20. https://www.nature.com/articles/modpathol2011185
  21. https://saspublishers.com/media/articles/SJMCR_124_567-570.pdf
  22. https://www.ncbi.nlm.nih.gov/books/NBK507721/
  23. https://www.pathologyoutlines.com/topic/vaginafibroepithelial.html
  24. https://pmc.ncbi.nlm.nih.gov/articles/PMC10027795/
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC6587646/
  26. https://www.sciencedirect.com/science/article/pii/S221026122201104X
  27. https://doi.org/10.3390/diagnostics13050924
  28. https://ascopubs.org/doi/10.1200/JCO.19.00576
  29. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.21138
  30. https://www.ncbi.nlm.nih.gov/books/NBK65802/
  31. https://pmc.ncbi.nlm.nih.gov/articles/PMC11497283/
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC11127508/
Add your contribution
Related Hubs
User Avatar
No comments yet.