Chondroid Syringoma

Etiology

The etiology of chondroid syringoma remains unclear, but it is believed to originate from pluripotent cells within the sweat gland ductal epithelium.[4] Some studies suggest a potential association with trauma, chronic irritation, or hormonal influences, although no definitive causal factors have been identified. Histologically, chondroid syringoma exhibits a biphasic pattern with both epithelial and mesenchymal components, characterized by nests of basaloid epithelial cells and areas of chondroid or myxoid stroma.[6] While the tumor typically presents as a slow-growing, painless, solitary nodule, diagnosis primarily relies on histopathological examination. Although some recent developments have been made to identify genomic aberrations of various salivary gland tumors, further research is needed to elucidate the precise etiology and pathogenesis of chondroid syringoma.[7]

Epidemiology

Chondroid syringoma is a relatively uncommon benign tumor arising from sweat gland structures, most frequently observed in the head and neck area. While precise epidemiological data on chondroid syringoma are limited, this neoplasm predominantly affects adults, with a slight predominance in men.[4] The condition typically manifests between the third and sixth decades of life; pediatric cases have been reported.[8][9] 

There is a consensus that chondroid syringoma is rare, comprising less than 0.01% of all primary skin tumors.[10][11] Although it can occur sporadically, some reports suggest an association with previous trauma or chronic irritation at the tumor site. However, further research is warranted to establish more comprehensive epidemiological characteristics and risk factors associated with this condition.

Pathophysiology

Mixed tumors of the skin originate from eccrine or apocrine sweat glands or their ductal structures.[3] The exact pathophysiological mechanisms underlying chondroid syringoma development remain unclear. The condition is believed to arise from pluripotent myoepithelial cells within the sweat gland ductal epithelium, undergoing differentiation towards both epithelial and mesenchymal components. The epithelial component usually consists of apocrine or eccrine differentiation, while the mesenchymal components are generally a chondroid or myxoid stroma.[12] Therefore, histologically, chondroid syringoma demonstrates a biphasic pattern characterized by nests of basaloid epithelial cells surrounded by a chondroid or myxoid stroma.

PLAG1 gene rearrangements have been identified in a significant number of chondroid syringomas.[13] More than 87% of apocrine-type cutaneous mixed tumors overexpress PLAG1. However, eccrine-type cutaneous mixed tumors lack PLAG1 expression.[12] Pleomorphic adenoma, chondroid syringoma's homologous neoplasm of the salivary gland, lung, and breast, also demonstrates PLAG1 fusions.[12]

Despite the limited understanding of its pathophysiology, chondroid syringoma is recognized as a benign tumor with low recurrence rates following surgical excision, underscoring its relatively indolent nature. Continued research efforts to unravel the molecular mechanisms driving chondroid syringoma development may provide insights into its pathophysiology and potentially identify novel therapeutic targets.

Histopathology

Chondroid syringoma exhibits distinctive histopathological features that aid in its diagnosis (see Image. Cutaneous Mixed Tumor at 2x Magnification). Histologically, chondroid syringoma demonstrates a circumscribed dermal or subcutaneous tumor with a biphasic pattern characterized by nests or cords of basaloid epithelial cells surrounded by islands or strands of myoepithelial cells within a chondromyxoid or myxoid stroma.[13][14] The basaloid cells typically form duct-like structures, while the myoepithelial cells appear spindled or stellate. A spectrum of differentiations exists for both the epithelial and stromal components. Epithelial alterations include apocrine, eccrine, or less commonly follicular, sebaceous, or plasmacytoid differentiation. The various stromal components that have been identified include myxoid, chondroid, or less commonly collagenous, osteoid, or lipoid metaplasia.[15] 

Further, chondroid syringoma can be subclassified based on histologic characteristics into the most common apocrine type or the rarer eccrine type.[16] The apocrine variety typically involves differentiation toward hair follicle and sebaceous gland structures, with an epithelial part made up of branching tubules and cyst-like spaces set in a myxoid or chondromyxoid stroma (see Image. Cutaneous Mixed Tumor at 10x Magnification). The tubules consist of 2 layers: an outer layer of myoepithelial cells and an inner layer of epithelial cells, which sometimes exhibit secretion through decapitation.[17] In the eccrine type, the epithelial part consists of small tubes lined with 1 layer of uniform cells that are either cuboidal, oval, or round. These cells have a cytoplasm that is either eosinophilic or has a clear, glass-like appearance and vesicular nuclei. There is no decapitation secretion present.

Immunohistochemical staining plays a valuable role in confirming the diagnosis of chondroid syringoma and distinguishing it from other cutaneous neoplasms. Commonly used immunohistochemical markers include cytokeratin, epithelial membrane antigen (EMA), S-100 protein, and smooth muscle actin (SMA). Cytokeratin and EMA typically show positive staining in the epithelial component of chondroid syringoma, highlighting the ductal structures. S-100 protein and SMA, on the other hand, demonstrate positive staining in the myoepithelial cells, aiding in identifying this component within the tumor.[12] The characteristic histopathological features and immunohistochemical staining patterns help accurately diagnose chondroid syringoma and differentiate it from other benign and malignant cutaneous neoplasms.

History and Physical

The clinical presentation of mixed tumors is indistinctive. These neoplasms can present with varying morphology but are most commonly misdiagnosed as cysts. The history and physical examination of a patient with chondroid syringoma play a critical role in diagnosis and management. Clinical evaluation typically involves a comprehensive assessment of the patient's medical history and a thorough examination of the lesion.

History-taking should include inquiries about the lesion's onset, duration, progression, and associated symptoms, such as pain, tenderness, or changes in size. Patients may report a slow-growing, painless nodule present for months to years, often in the head and neck region, particularly around the eyelids or nose (see Image. Cutaneous Mixed Tumor). Additionally, clinicians should inquire about any relevant past medical history, including previous skin lesions, trauma, or radiation exposure.

The physical examination of a chondroid syringoma typically reveals a well-defined, firm, mobile nodule within the dermis or subcutaneous tissue. The overlying skin may appear normal or show erythematous, ulcerative, or crusting features. Lesions are often solitary but can occasionally be multiple. Size and location may vary, with some lesions being small and superficial while others may be larger and deeper-seated. While the history and physical examination provide valuable clues, definitive diagnosis typically requires histopathological examination of a tissue biopsy or excisional specimen.

Evaluation

Evaluation typically involves a combination of clinical assessment, histopathological examination, and, in some cases, immunohistochemistry to confirm the diagnosis and assess the extent of the tumor. While there are no current guidelines and limited literature specifically addressing the evaluation of chondroid syringoma, recent studies have highlighted the role of various diagnostic modalities in its assessment. Histopathological examination remains the gold standard for diagnosing chondroid syringoma.[7] Tissue biopsy or excisional biopsy of the lesion allows for microscopic evaluation, revealing characteristic features such as nests of basaloid cells, tubular structures, and areas of chondroid or myxoid stroma. Fine-needle aspiration has also been reported as an initial biopsy method for deeper subcutaneous tumors.[18][19] Immunohistochemistry may be utilized to support the diagnosis, with markers such as cytokeratin, EMA, and S-100 protein often showing positive staining patterns consistent with chondroid syringoma.

Imaging studies such as ultrasonography, magnetic resonance imaging (MRI), or computed tomography (CT) may help characterize the lesion's depth, relationship to surrounding structures, and potential involvement of deeper tissues, particularly in larger, subcutaneous, or recurrent cases where more complex surgical planning is necessary.[20] Ultrasonography is often used as an initial imaging modality due to its accessibility and ability to assess superficial lesions; MRI or CT may provide additional information in cases of larger or deeper lesions.[21] While specific laboratory tests are not typically indicated for evaluating chondroid syringoma, a complete blood count and a comprehensive metabolic panel may be performed as part of a preoperative assessment or to evaluate any underlying systemic conditions.

Treatment / Management

Chondroid syringoma treatment typically involves surgical excision, which is considered curative in most cases.[10] The primary goal of surgical intervention is complete removal of the tumor with adequate margins to minimize the risk of recurrence and, although extremely rare, avoid malignant transformation. The extent of excision depends on factors such as tumor size, location, and depth of invasion. While chondroid syringoma is generally well-demarcated and encapsulated, careful dissection is essential to prevent damage to surrounding structures and ensure complete excision.

Moreover, although recurrence rates following surgical excision are generally low, the possibility of recurrence necessitates long-term surveillance and follow-up care to ensure optimal patient outcomes. Recurrent lesions may require additional surgeries, potentially increasing patient morbidity and healthcare costs. In cases where surgical excision is not feasible due to tumor size, location, recurrence, or patient comorbidities, alternative treatment modalities such as Mohs micrographic surgery or radiation therapy may be considered.[22] However, the efficacy of these approaches in chondroid syringoma management remains less established, and further research is needed to delineate their role.(B3)

Due to its rarity, guidelines for the management of patients with chondroid syringoma are limited. Therefore, treatment decisions are typically guided by expert consensus and clinical experience. Histopathological examination of the excised specimen is essential for confirming the diagnosis and assessing margins to ensure complete tumor removal. Genetic studies and immunohistochemical markers may provide insights into tumor behavior and aid in risk stratification.

Differential Diagnosis

When evaluating a patient with a suspected chondroid syringoma, it is essential to consider a range of differential diagnoses due to its nonspecific clinical presentation. Key conditions to include in the differential diagnosis to ensure accurate identification and management include:

• Epidermal inclusion cyst: A benign entity, which chondroid syringoma is often misdiagnosed as, based on clinical features
• Eccrine spiradenoma: Another benign adnexal tumor originating from eccrine sweat glands, which can resemble chondroid syringoma histologically
• Trichoepithelioma: A benign hair follicle tumor that may show overlapping histological features with chondroid syringoma, including basaloid cells and myxoid stroma
• Pilomatricoma: A benign skin tumor derived from hair matrix cells, which may exhibit calcification and chondroid differentiation histologically
• Dermatofibroma: A common benign skin lesion that can sometimes mimic chondroid syringoma clinically, especially when presenting as a firm, nodular lesion
• Dermatofibrosarcoma protuberans: A rare, locally aggressive soft tissue tumor that may share histological similarities with chondroid syringoma, such as a storiform pattern
• Adnexal carcinomas (eccrine carcinoma, apocrine carcinoma): Malignant adnexal tumors that may resemble chondroid syringoma histologically, particularly in cases of poorly differentiated or metastatic carcinoma
• Basal cell carcinoma: The most common malignant skin tumor, which may display diverse histological patterns, including those resembling chondroid syringoma, such as cribriform or trabecular patterns
• Cutaneous metastases: Cutaneous metastases from various internal malignancies can mimic chondroid syringoma clinically and histologically (rare)
• Neurofibroma: A benign peripheral nerve sheath tumor occasionally demonstrates histological overlap with chondroid syringoma, particularly in cases with myxoid stroma
• Syringoma: A benign tumor of eccrine sweat duct origin, which can mimic chondroid syringoma clinically, especially in cases presenting as multiple, small papules

Prognosis

Chondroid syringoma typically carries an excellent long-term prognosis due to its benign nature, particularly when the tumor is diagnosed early and fully excised. Complete surgical removal usually leads to resolution without significant long-term complications.[23] Although it may occasionally recur after surgical excision, recurrence rates are low, ranging from 2% to 9%, according to various study results.[22][24][25] 

The risk of malignant transformation is exceedingly rare, with only a few documented cases reported in the literature.[25][26] Malignant chondroid syringoma most commonly occurs on the extremities.[20] Furthermore, metastasis has not been observed in chondroid syringoma.

Complications

Complications associated with chondroid syringoma are generally rare due to its benign nature; however, certain factors can lead to potential challenges in management. First, misdiagnosis or delayed diagnosis may occur due to the rarity of this condition and its varied clinical presentation, potentially resulting in inappropriate treatment or unnecessary patient anxiety. Moreover, incomplete excision of the tumor during surgery can lead to recurrence, albeit infrequent, requiring additional interventions and potentially impacting patient outcomes. Careful surgical planning and meticulous dissection are essential to minimize the risk of recurrence. Surgical complications may include wound infection, hematoma formation, nerve injury, or cosmetic deformity—particularly in cases involving lesions in cosmetically sensitive areas such as the face.