Solitary Superficial Angiomyxoma in an Uncommon Location: A Case Report and Literature Review

Superficial angiomyxoma (SAM) is a rare, benign, and slow-growing soft tissue tumor with a tendency for frequent local recurrence. Most SAMs are solitary and sporadic. However, multiple SAMs, particularly on the external ear or eyelids, may be the initial or only sign of the Carney complex, an autosomal dominant syndrome that impacts various organs, including the heart, breasts, and skin, and is linked to endocrine hyperactivity. To ensure an accurate diagnosis, a comprehensive patient interview, physical examination, and laboratory tests, including endocrine-specific markers and imaging studies, are essential. Due to the high risk of recurrence, especially in large, encapsulated lesions, complete surgical excision is the preferred treatment approach. We present a case of a 24-year-old female with SAM on the shoulder, review the relevant literature, and discuss the pathogenesis and appropriate management of such cases.


Introduction
Superficial angiomyxoma (SAM), first described in 1985, is a relatively under-recognized cutaneous tumor.In 1988, Allen et al. classified angiomyxomas into two subtypes: aggressive and superficial [1].Aggressive angiomyxoma, a rare myxoid neoplasm, predominantly affects the genital, perineal, and pelvic regions in young women, suggesting estrogen's role in its growth [2].In contrast, SAM can occur at any age, with a slight male predominance, and is most common in the third to fourth decade of life.Pediatric cases, particularly in the genital area, are rare [2].Angiomyofibroblastoma, added later to the classification, is now considered a third subtype of angiomyxoma [3].
SAM typically appears as a slow-growing, asymptomatic solitary nodule or polypoid lesion less than 5 cm in diameter, often with a multilobular or multinodular form.It most frequently arises on the trunk, head and neck, and lower extremities and rarely affects the breasts or eyelids.
The presence of multiple SAMs should prompt consideration of the Carney complex, a rare syndrome featuring cutaneous myxomas, mammary myxomas, cardiac myxomas, lentigines, endocrine hyperactivity, and psammomatous melanotic schwannoma.SAM may be the earliest or sole manifestation of this syndrome.
Immunohistochemical studies indicate that loss of PRKAR1A protein expression is involved in SAM development [4].This loss may result from genetic defects, epigenetic abnormalities (such as DNA hypermethylation), or protein-related deviations (like posttranscriptional modifications).Thus, PRKAR1A immunostaining is a crucial diagnostic tool, particularly for distinguishing SAM from other myxoid lesions in small biopsy specimens [4].
Given the high rate of local recurrence (30-40% after incomplete resection) [5], complete surgical excision is the treatment of choice.Mohs micrographic surgery may be considered for difficult-to-treat areas where preserving tissue for cosmetic reasons is essential.

Case Presentation
A 24-year-old female, with no significant personal or familial medical history, presented to our clinic with a slowly enlarging nodule on her left shoulder that had been present for one year.The skin examination revealed a well-defined, skin-colored nodule with fine superficial vessels on the surface, measuring 7 cm in An excisional biopsy was performed (Figure 2), and the histopathologic examination revealed a well-defined, encapsulated tumor mass.The tumor exhibited monomorphous spindle-shaped cells with small nuclei, prominent nucleoli, reduced cytoplasm, and thin-walled blood vessels embedded in a myxoid stroma.No pleomorphism, nuclear atypia, or necrosis was observed (Figure 3).Tumor cells stained intensely positive for CD34 and were only focally positive for actin, but negative for SOX10, calponin, and MUC4.The Ki-67 proliferation index was 10-12%.To prevent recurrence, the patient underwent a wide surgical excision.The H&E stain reveals a well-defined, encapsulated tumor mass with monomorphous spindle-shaped cells, small nuclei, reduced cytoplasm, and thin-walled blood vessels embedded in abundant myxoid stroma.The tumor shows no pleomorphism or nuclear atypia (H&E, A: 12.5×, B: 25×, and C: 200×).
Due to the particularities of the case -a large tumor, more than 5 cm in diameter, in contact with bone affecting a young female patient -she was referred to an endocrinologist, and additional laboratory analyses were conducted to rule out endocrine hyperactivity.Levels of intact parathormone, vitamin D, prolactin, growth hormone, insulin-like growth factor 1, and thyroid-stimulating hormone were within normal limits.Additionally, cardiac and thyroid ultrasounds did not reveal any pathological findings.Consequently, the Carney complex was ruled out.

Systematic literature review
To better understand the epidemiology and progression of SAM, we conducted a review of the medical literature.We searched for the term "solitary angiomyxoma" using PubMed and Google Scholar, identifying 88 relevant publications (Table 1) .We analyzed data from these studies, focusing on lesion location, age at diagnosis, patient gender, and recurrence rates during follow-up.The review followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines (Figure 4) [89].Out of 123 records identified, 35 were review articles and were excluded.The remaining 88 records, detailing SAM cases, were included in both the qualitative and quantitative analyses.

Location
Age   Of the 123 records identified through database searching, 35 were review articles and were excluded.The remaining 88 records, detailing SAM cases, were included in the qualitative and quantitative synthesis.
PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses; SAM, superficial angiomyxoma Out of the 88 publications, seven presented case series with four to 54 patients [1,4,6-10], while the remaining were case reports.In total, 298 SAMs have been reported in 295 patients.Cases were reported across all ages, including three congenital SAMs in female patients located on the scalp, parotid region, and vulva.The oldest patient was 91 years old, with a mean age of 37.9 years.Of the 295 patients, 150 were female, resulting in a female-to-male ratio of 1.03.
Tumor locations included 53 cases (17.7%) on the trunk, particularly the lower back; 46 cases (15.4%) on the breasts, with 13 (4.3%)involving the nipple-areola region; 44 cases (14.7%) in the head and neck region, including three on the eyelid, one in the eye socket, two on the external ear, three in the parotid region, and three on the scalp; 41 cases (13.7%) on the lower limbs, including two on the soles (0.6%); 37 cases (12.4%) in the genital area, with tumors in the vulva (27 cases), vagina (one case), scrotum (eight cases), penis (one case), and epididymis (one case).Less common sites included the upper limbs (13 cases or 4.3%), fingers/toes (seven cases or 2.3%, including three subungual SAMs), and the inguinal region (four cases or 1.3%).SAMs also developed in the oral mucosa (10 cases or 0.3%), retropharyngeal area (one case or 0.3%), larynx (one case or 0.3%), and nasal vestibule (one case or 0.3%) (Figure 5).

SAM, superficial angiomyxoma
The majority of patients underwent complete surgical excision, although Mohs micrographic surgery, shave biopsy, and laser treatment were also used.Follow-up intervals varied from six months to two years.Recurrence occurred in 25 tumors, often after incomplete excision, with four tumors recurring twice.The time to recurrence ranged from eight months to 20 years.
SAM is a rare, slow-growing benign soft tissue tumor with a significant risk of local recurrence.Diagnosis relies on clinical presentation and histopathologic features, though additional diagnostic methods can be helpful.Dermoscopy may reveal the "red planet sign" -reddish translucent globules with fine superficial vessels [46].Ultrasonography can assist in the initial diagnosis by showing an irregular, heterogeneously echogenic cystic and solid lesion with multiple thin echogenic septa and micro-lobulated margins [5,64].CT scans show similar heterogeneity with variable enhancement, while MRI typically shows a homogeneous tumor with fluid-like signal intensity and variable heterogeneous enhancement on contrast-enhanced images [5].
Despite its benign nature, SAM's high recurrence rate post-excision and potential for rare muscle infiltration underscore the importance of Mohs micrographic surgery for small tumors to ensure clear margins.Larger, encapsulated lesions often require traditional excision.Long-term follow-up is essential, as recurrences may appear many years after the initial resection.

Conclusions
Due to its rarity and subtle histological features, SAM necessitates thorough evaluation by experienced pathologists and careful correlation with clinical findings (age, gender, location, and symptoms) for an accurate diagnosis.Additional diagnostic tools, such as dermoscopy, ultrasonography, CT, and MRI, can aid in differential diagnosis.A complete surgical excision is crucial for achieving a favorable aesthetic and functional outcome, given the tumor's significant potential for local recurrence, which can occur even decades after the initial diagnosis.We aim to raise awareness about this uncommon tumor and emphasize the importance of close monitoring for affected patients.

FIGURE 1 :
FIGURE 1: Well-defined, skin-colored nodule with fine superficial vessels on the surface, measuring 7 cm in diameter.The nodule is located on the left shoulder and is surrounded by normal skin.

FIGURE 2 :
FIGURE 2: Macroscopic appearance of a partially encapsulated, highly vascular cutaneous tumor.The tumor displays a smooth surface, bosselated contours, and a pink color, measuring 5 × 4 cm.

FIGURE 5 :
FIGURE 5: Distribution of SAM cases reported in the literature according to tumor location.

TABLE 1 : SAM cases reported in the medical literature.
SAM, superficial angiomyxoma; UA, unavailable information