A poroma is a benign adnexal neoplasm originating from the intraepidermal portion of the sweat gland duct, known as the acrosyringium. It is often grouped within the greater classification of acrospiroma that also includes dermal duct tumors, hidroacanthoma simplex, and nodular, clear cell, and poroid hidradenomas. Poroma was first described by Pinkus et al. in 1956 and was initially classified as a tumor originating from the eccrine sweat gland. Over time, this classic description has been challenged, and more recent data suggest that apocrine components may be present as well. In 1963, Pinkus and Mehregan wrote an original report detailing the first case of eccrine porocarcinoma arising from the intraepidermal ductal portion of the eccrine sweat gland. These malignant tumors may arise de novo or may develop from a pre-existing poroma through degenerative progression. The percentage of porocarcinomas transformed from benign eccrine poroma has been reported to be as high as 100% in a study by Shaw et al. sampling 27 cases. When looking at the actual transformation rates of the benign counterparts, however, it has been found that only 18% of poromas went on to become porocarcinoma. While the exact etiology remains unclear, the progression to malignancy appears to take a mean of 8.5 years. In this review, we will be highlighting the known facts about eccrine and apocrine poromas as well as eccrine porocarcinoma. We will begin with a discussion of clinical presentation, epidemiology, and risk factors for each of the conditions. We will then progress on to histologic, dermatoscopic, and immunohistochemical findings. The differential diagnoses for both tumors will be listed, and consideration will be given to their individual features. Finally, we will conclude with a review of management strategies.
Poroma is a benign adnexal neoplasm of the terminal sweat gland duct. Although poromas have traditionally been thought to originate from the eccrine sweat gland, there have been cases of apocrine etiology as well. Eccrine and apocrine poromas typically present as erythematous or flesh-colored nodules on the palms and soles. As these features overlap with a multitude of differential diagnoses, it is imperative to have a firm understanding of the characteristics that make the diagnosis of poroma. In addition, the malignant counterpart to the poroma, the eccrine porocarcinoma, manifests in a similar nonspecific fashion. Case studies and literature reviews have contributed immensely to our present knowledge of poroma and porocarcinoma. Given the rarity of these neoplasms, however, there remains a relative paucity of information on atypical presentations and rates of malignant transformation. In this article, the epidemiology, clinical presentation, diagnosis, and management of poroma and porocarcinoma will be reviewed. This systematic approach may serve as a guide in navigating the diagnostic dilemma of these rare cutaneous lesions.
Clinically, a poroma typically presents as solitary dome-shaped papule, plaque, or nodule. It is commonly described as skin-colored, pink, red, white, or even blue. Its surface can range from smooth to verrucous, and it has been described as ulcerative in some cases. While a poroma is generally found on an acral location, it can be located on almost any cutaneous surface. Its most common location is on the palmar or plantar surface (Fig. 1). It is important to note that poroma has been documented on the trunk, face (Fig. 2), and neck as well. It is generally slow growing and asymptomatic for the patient, although some patients may experience pain and itching. In rare cases, the patient may present with poromatosis and have multiple acral or widespread poromas at the time of diagnosis. Eccrine porocarcinoma presents as a firm, commonly asymptomatic nodule that is erythematous to violaceous in color and usually <2 cm in size (Fig. 3). It tends to appear more exophytic and ulcerative than a benign poroma. In the setting of a pre-existing poroma, malignant transformation of these lesions may be identified by recurrence, spontaneous bleeding, ulceration, sudden itching, pain, or accelerated growth in a short period of time. Like their benign counterparts, porocarcinomas appear most commonly on the lower extremities, followed by the trunk, head, upper limbs, and neck in descending order of occurrence. Isolated cases have been studied on the vulva, breast, and nail beds as well.[13-15]
Epidemiology and risk
Eccrine and apocrine sweat gland tumors are believed to constitute as few as 1% of primary cutaneous lesions. A relatively rare tumor, poroma comprises approximately 10% of these lesions. It tends to occur in the middle age to elderly population and does not appear to have a predilection for race or sex. Several correlations have been found between long-term radiation exposure and the development of poroma. Specifically, there have been examples of poroma diagnosed in patients who had electron beam therapy for mycosis fungoides as well as in areas of chronic radiation dermatitis. In addition, poroma has also been found to occur in patients with other skin diseases, including hypohidrotic ectodermal dysplasia and Bowen's disease. Occasionally, a poroma may be found as a secondary lesion within a nevus sebaceus. Eccrine porocarcinoma has a lower incidence than poroma and is estimated to constitute 0.005–0.01% of all skin cancers. Porocarcinomas occur more often in the sixth to eighth decades of life. They occur in all races and both sexes, yet have been reported slightly more often in females. Like poroma, porocarcinoma has also been shown to arise following chronic radiation exposure. Additional associations that have been implicated include extramammary Paget's disease, sarcoidosis, chronic lymphocytic leukemia, pernicious anemia, Hodgkin's disease, nevus sebaceus, HIV, and xeroderma pigmentosum.
Histologically, a poroma is a well-circumscribed tumor composed of proliferative cuboidal or poroid cells that commonly extend from the basal epidermis into the dermal layer (Fig. 4). Depending on the location of the poroid cells in relation to the epidermis, a poroma can be categorized into the acrospiroma variants as described above. It may be entirely intraepidermal, such as hidroacanthoma simplex, wholly juxtaepidermal, or entirely intradermal such as dermal duct tumors. Poroid and nodular hidradenomas exclusively reside in the dermal layer and are classified based on whether they show eccrine or apocrine differentiation. Within the epidermis, poroid cells are sharply differentiated from the adjacent keratinocytes. These cuboidal cells have monomorphous ovoid nuclei with a non-palisading pattern and inconspicuous nucleoli (Fig. 5). The cells have a characteristic compact eosinophilic cytoplasm that stains periodic acid-Schiff-positive. Although benign, poromas may possess histological characteristics that are more commonly seen in descriptions of malignant neoplasms. These include the presence of a variable number of mitotic figures, foci of necrosis en masse, and a highly vascularized stroma. In some cases, a poroma may display a clear cell change with small nuclei surrounded by a pale cytoplasm. The aggregates of poroid and cuticular cells in a poroma may show ductal or tubular formation. The degree of ductal differentiation can vary between poromas. Some have a multitude of ductal foci whereas others may be harder to analyze. Carcinoembryonic antigen immunostaining can identify the presence of both eccrine and apocrine ducts and thus help in the identification. If the poroma displays more tubular foci lined by columnar cells with holocrine secretions, this may be highly suggestive of an apocrine etiology. It is thought that a poroma with sebaceous differentiation is most likely to be of folliculosebaceous–apocrine lineage. Porocarcinoma is described as a collection of anaplastic cells spanning the epidermis and extending into the dermis (Fig. 6). In some situations, these anaplastic cells may be located next to cells of the benign poroma, if not extending from them. The malignant cells are glycogen-rich and contain large, irregular, and hyperchromatic nuclei. Acanthosis may be seen secondary to the proliferation of intraepidermal tumor cell nests (Fig. 7). The dermis will frequently show mitotic figures and areas of necrosis. When evaluating these tumors, it is important to rule out the possibility of metastasis from a primary adenocarcinoma. This is commonly done with verification of ductal structures and a periodic acid-Schiff-positive cuticle. Porocarcinomas undergo a proliferative phase within the epidermis and may proceed to local invasion of the papillary and reticular dermis. These cells can invade the dermal lymphatics and have shown regional and distant metastases.
The utility of dermatoscopy has been reported with regard to the differential diagnosis of pigmented lesions. In light of this, several researchers have investigated how this may translate to the diagnosis of a poroma. As some poromas are not pigmented, it has been postulated that the vascular pattern is perhaps the most prominent dermatoscopic finding to aid in diagnosis. Among the vascular patterns commonly seen are the polymorphic, glomerular, linear-irregular, leaf and flower-like, and looped or hairpin variants (Fig. 8). Although polymorphic vascular patterns may be seen in other lesions such as melanoma and thus prompt further investigation, the leaf and flower-like pattern appears to be relatively unique to the poroma. Furthermore, the vascular pattern of a poroma is in considerably less focus than the arborizing vessels of basal cell carcinoma, suggesting that those in the poroma are located much deeper in the dermis and providing an alternative method for differentiating the lesions. In a study by Ferrari et al. a white-to-pink halo was the predominant feature seen among cases of eccrine poroma. This was thought to be due to fibrinoid edema surrounding dilated vessels of the tumor. Additional dermatoscopic features included the presence of vascular blush, secondary to the vasodilatation and high vascular volume of these tumors, as well as structureless areas and interlacing white cords (Fig. 8). This latter finding of interlacing white cords is quite specific to the poroma and has only been found in other lesions in two isolated cases of melanoma. Dermatoscopic studies on eccrine porocarcinomas show similar vascular patterns to those observed in poromas but tend to be more conspicuous and irregular. This atypical vascular pattern is not specific to the porocarcinoma and is commonly seen in the evaluation of other skin malignancies. What appears to differentiate the porocarcinoma from these lesions is the combination of the vascular pattern with the presence of white globular structures within a light brown background (Fig. 9).
It was previously thought that p53 protein expression could potentially be a method in which to differentiate poroma from porocarcinoma. In 2001, Akalin et al. examined p53 protein expression by immunohistochemistry on a sample of 25 eccrine poromas and 11 porocarcinomas. Among these, 22 of the 25 poromas as well as eight of the 11 porocarcinomas showed expression. This was further stratified based on the percentage of cells that were reactive for p53 and categorized this as low (<5%), moderate (5–50%), and high (>50%) as well as for the intensity of staining. They concluded that eccrine poroma had significant p53 expression that paralleled that of the porocarcinoma. As such, they determined that although p53 may play some role in the oncogenic pathway to carcinoma, it could not be used as a stand-alone marker for malignancy. Additional studies have sought to further elucidate the molecular basis of poroma and porocarcinoma by investigating the expression of p16, retinoblastoma protein, and their relationship through immunohistochemical studies. It was determined that nearly all of the porocarcinomas showed strong immunoreactivity for p16 in the nuclei and cytoplasm whereas their benign counterparts were nonreactive. In addition, staining for retinoblastoma showed an inverse relationship and was uniformly negative for the porocarcinoma samples but sparsely positive among the poromas. They were able to conclude that overexpression of p16, as well as loss of retinoblastoma, could potentially be used as a useful diagnostic test on routine laboratory screening.
Among the differential diagnoses of eccrine poroma are the aforementioned basal cell carcinomas, which can often be differentiated through dermatoscopic evaluation of the lesion. Seborrheic keratosis can also be in one's differential, especially if the tumor is located intraepidermally or juxtaepidermally. In contrast to poromas, seborrheic keratosis would not show the ductal differentiation on histologic exam and may include the presence of horn cysts or other distinguishing clinical features. Hidradenomas may be in the differential, yet its epithelial cells would be larger with more noticeable pale or clear cytoplasm than the compact cuboidal cells seen in poromas. Additional differential diagnoses that have been postulated include pyogenic granulomas, acrochordons, verrucae, and other adnexal tumors. An outline of the clinical and histologic characteristics of each diagnosis are listed in Table 1.[7, 18, 22, 31-34] The differential diagnosis of eccrine porocarcinoma parallels that of eccrine poroma with a few additions. In addition to those diagnoses listed in Table 1, differentials for porocarcinoma include squamous cell carcinoma, Bowen's disease, Paget's disease, and amelanotic melanoma. An outline of the clinical and histologic characteristics of these diagnoses are listed in Table 2.[12, 18, 35, 36]
|Eccrine poroma||Solitary flesh-colored or pigmented papule, plaque, or nodule with a smooth or verrucous surface commonly located on the acral surfaces of middle-aged to elderly men and women||Cuboidal cells of eccrine lineage with monomorphous ovoid nuclei and a highly vascularized stroma. May have necrosis en masse or clear cell change.||Shalom et al. Drummer|
|Basal cell carcinoma||Pearly papules with telangiectasias, rolled edges, and central ulceration located on sun-exposed areas after the 4th decade. More common in men.||Basaloid cells with large hyperchromatic, oval nuclei with little cytoplasm and no intercellular bridges. Rare mitotic figures and palisading nuclei.||Orengo et al.|
|Seborrheic keratosis||Flat, greasy, pigmented squamous epithelial proliferation with keratin-filled cysts commonly located on the head, neck, and extremities of elderly men and women.||Raised proliferation of basaloid cells with expansile growth and rete ridges, keratin filled cysts, acanthotic or hyperkeratotic pattern. Some cells contain melanin.||Grant-Kels|
|Hidradenoma||Solitary flesh colored, red, or blue solid or cystic nodules most commonly located on the trunk, head, and extremities of middle-aged to elderly women.||Circumscribed unencapsulated tumor within the dermis and subcutaneous tissue. May have cystic, mucinous areas within tumor cells. Eccrine differentiation with eosinophilic or clear cell components.||Storm et al.|
|Pyogenic granuloma||Solitary, erythematous dome-shaped nodule that bleeds easily and may occur after trauma. Most common in children on hands, feet, head, and neck. Also seen on the oral mucosa of pregnant women.||Proliferation of capillaries embedded in an edematous stroma; dense infiltration of polymorphonuclear leukocytes with granulation tissue; erosion of overlying epidermis.||Requena et al. Patrice et al.|
|Cylindroma||Solitary slow growing firm pink nodules. Most common in middle-aged women.||Jigsaw pattern of tumor cells in dermis surrounded by matrix of basement membrane. Dark basaloid and clear cells.||Storm et al.|
|Acrochordon||Flesh-colored hanging or protruding polyps commonly found in intertriginous areas in men and women before the 5th decade.||Polypoid projection with a smooth surface, flattened rete ridges and fibrillated collagen in central core. Variant has a verrucous surface with papillated epidermal hyperplasia and acanthosis.||Grant-Kels|
|Verruca vulgaris||Hyperkeratotic flesh-colored papules with a rough, irregular surface occurring most commonly on the hands and knees of children and adolescents.||Digitated epidermal hyperplasia, hyperkeratosis, koilocytosis in granular layer. Dilated capillaries in papillae with parakeratotic cells with entrapped red blood cells above the tips of the digitations.||Grant-Kels|
|Eccrine porocarcinoma||Erythematous to violaceous ulcerative or exophytic firm nodule commonly located on the extremities, trunk, head, and neck of females>males in the 6th to 8th decade||Anaplastic, glycogen-rich cells with eccrine ductal structures, nuclear atypia, and necrosis. May be adjacent to a benign poroma||Brown et al.12|
|Squamous cell carcinoma (SCC)||Erythematous hyperkeratotic or ulcerative plaque, nodule, or tumor on the sun-exposed areas of elderly men and women||Hyperkeratosis, epidermal hyperplasia and islands of squamous cells with central keratinization (keratin pearls). May see a dermal mixed inflammatory infiltrate||Grant-Kels18|
|Bowen's disease (Squamous cell carcinoma in situ)||Well-circumscribed erythematous plaque on a non sun-exposed area||Clonal keratinocytic proliferation with or without full thickness atypia With cytoplasmic bridges but no mucin or GCDFP-15||Grant-Kels18|
|Paget's disease||Macular erythema with a sharply defined border and possible erosion or crusting commonly associated with breast carcinoma or internal malignancy||Epidermis infiltrated by neoplastic cells with pale, expanded neoplasm. No intercellular bridges, positive for mucin and GCDFP-15||Grant-Kels18|
|Amelanotic melanoma||Erythematous macule or patch on sun exposed areas, plaque or nodule without epidermal change, or exophytic nodule commonly on head, neck, upper and lower extremities.||Epithelioid, spindled, or desmoplastic morphology. Nuclear atypia, solar elastosis, poorly differentiated cells without melanin|| |
Cheung et al.35
Gualandri et al.36
Although apocrine poroma shares many similarities with eccrine poroma, its various distinctions warrant a separate discussion when considering the differential diagnoses above. Apocrine poroma was first described by Requena et al. in 1988. Since then, its existence as a separate entity from eccrine poroma has been validated by several reports in the literature. Clinically, the apocrine poroma presents in a similar manner to its eccrine equivalent. What sets it apart, however, are the findings of a homogeneous eosinophilic intraluminal secretion and lining cells with eosinophilic cytoplasm that suggest the presence of decapitation secretion and apocrine lineage. Additional unique features include the presence of sebaceous cells lined by poroid cells as well as foci of follicular differentiation in the periphery. As they combine features of sebaceous, apocrine, and follicular differentiation, the name apocrine poroma may serve as an umbrella term for the amalgamation of similar neoplasms that have been described in the past. These include infundibular adenoma, complex poroma-like adnexal adenoma, and sebaceoma, among others.[2, 38-40]
Pigmented hidroacanthoma simplex
In addition to apocrine poroma, pigmented hidroacanthoma simplex is another variant of eccrine poroma that merits special consideration. As mentioned previously, hidroacanthoma simplex is the entirely intraepidermal form of eccrine poroma. An extremely rare tumor, pigmented hidroacanthoma simplex has been documented by relatively few case reports in the literature.[41-45] Clinically, these are described as brown to black scaly dome-shaped nodules. Histopathologic studies of these tumors have revealed the presence of dendritic melanocytes scattered within intraepidermal tumor nests. As poroma and hidroacanthoma simplex are not usually pigmented, their pigmented counterpart may often be misdiagnosed as a seborrheic keratosis, Bowen's disease, or malignant melanoma.[43, 45] Furthermore, there have been multiple reports of invasive porocarcinoma arising from a pigmented hidroacanthoma simplex.[41, 42] Given the implications of misdiagnosis, it is important to include pigmented hidroacanthoma simplex in one's differential.
As eccrine poroma is a benign adnexal lesion, treatment is curative. Superficial lesions may be treated with simple excision or with shave or electrosurgical destruction. Deeper lesions may be treated with simple excision. In contrast to its malignant counterpart, recurrence of eccrine poroma is rare. Treatment approaches for eccrine porocarcinoma include electrocautery, electrofulguration, simple excision, wide excision, Mohs micrographic surgery, radiation, and amputation. Porocarcinomas have been shown to have local recurrence, which occurs in about 20% of cases, lymph node metastases in 20%, and solid organ metastases in 10%. Given the high rate of local recurrence, wide surgical excision with broad tumor margins is generally considered the treatment of choice with cure rates as high as 70–80%. Radiation therapy and chemotherapeutic agents such as cyclophosphamide, bleomycin, cisplatin, and 5-fluorouracil have not shown great responses and are generally reserved for the treatment of metastatic disease. At this time, the survival time for patients with metastatic eccrine porocarcinoma is estimated to be between 5 and 24 months.
Poroma is a benign cutaneous tumor derived from the terminal portion of the sweat gland duct. Although it largely remains classified as a neoplasm of the eccrine sweat gland, apocrine etiology has been implicated in some cases. The clinical and histopathologic features of poromas closely parallel those of several other dermatologic conditions. As such, it is paramount that a careful evaluation of the patient presenting with poroma is undertaken to make the correct diagnosis. Modalities in which to achieve this include biopsy, immunohistochemical staining, and dermatoscopic evaluation. At this time, the treatment of eccrine and apocrine poromas consists of simple excision. If the lesion recurs after excision or presents with ulceration, bleeding, pain, or accelerated growth, one should maintain a suspicion of eccrine porocarcinoma and investigate the lesion accordingly. Although some porocarcinomas arise de novo, there are a sufficient number of tumors, up to 100% in some studies, which originate from poromas. Immunohistochemistry on excised specimens has been suggested as a method in which to identify the transformation to malignancy on a molecular level. Although there are numerous treatment options for eccrine porocarcinoma, interference at an early stage could prevent the high rates of local recurrence and metastasis. At this time, there is a paucity of information regarding the recurrence and malignant transformation rate of poroma. In the future, it will be interesting to see how an expansion of our current knowledge of poroma and porocarcinoma may alter the management and outcomes of these rare tumors.
Review questions (answers are available after references)
- 1.Which of the following statements are true?
- a.A poroma is a benign adnexal neoplasm of the intradermal portion of the sweat gland
- b.Poromas are most likely to occur in the second decade of life
- c.The most common location of a poroma is the back
- d.Patients with poromas are typically asymptomatic at the time of presentation
- e.Poromas typically transform into porocarcinomas within a 2-year period
- 2.Which of the following have not been implicated in the development of porocarcinoma?
- a.Chronic radiation exposure
- b.Prolonged use of chemotherapeutic agents
- d.Chronic lymphocytic leukemia
- e.Human immunodeficiency virus
- 3.A 60-year-old woman presents with a solitary, erythematous dome-shaped nodule on the left side of her face. The lesion has a small ulceration on its surface. She has noticed occasional itching and spontaneous bleeding. Which of the following characteristics is most suggestive of malignancy?
- a.Her age
- b.Occasional itching
- c.Erythematous color
- d.The location of the lesion
- e.Spontaneous bleeding
- 4.All of the following are histologic characteristics of eccrine poroma except:
- a.Extension of epidermal cells into the dermal layer
- b.PAS-negative cytoplasm
- c.Monomorphic cells with ovoid nuclei
- d.Highly vascularized stroma
- e.Foci of necrosis en masse
- 5.Which of the following patterns of immunohistochemical staining are representative of porocarcinomas?
- a.CEA negative, PAS positive, p16 immunoreactive, Rb nonreactive
- b.CEA positive, PAS positive, p16 immunoreactive, Rb nonreactive
- c.CEA positive, PAS positive, p16 immunoreactive, Rb immunoreactive
- d.CEA negative, PAS negative, p16 nonreactive, Rb non-reactive
- e.CEA positive, PAS negative, p16 immunoreactive, Rb immunoreactive
- 6.Acrospiromas are further classified based on their location within the sweat gland. Which of the following pairs are not correctly matched?
- a.Intradermal: dermal duct tumor
- b.Intraepidermal: hidroacanthoma simplex
- c.Intradermal: hidradenoma
- d.Juxtaepidermal: eccrine poroma
- e.Juxtaepidermal: hidradenoma
- 7.Which of the following vascular patterns have not been observed in the dermatoscopic evaluation of eccrine poroma?
- b.Flower and leaf
- 8.A 12-year-old boy presents with a solitary, erythematous, dome-shaped nodule overlying the plantar surface of his left foot. The lesion bleeds with minimal trauma and you suspect a diagnosis of pyogenic granuloma. Which of the following would you expect to see on histologic examination?
- a.Jigsaw pattern of tumor cells in the dermis
- b.Basaloid cells with palisading nuclei
- c.Cuboidal cells within a highly vascularized stroma
- d.Proliferation of capillaries in an edematous stroma
- e.Epidermal hyperplasia, hyperkeratosis, and koilocytosis
- 9.The rate of lymphatic invasion of eccrine porocarcinoma is approximately:
- 10.All of the following have been studied as treatment modalities for eccrine porocarcinoma except:
- c.Wide excision
- d.Mohs micrographic surgery
Answers to questions:
1. d 2. b 3. e 4. b 5. b 6. e 7. d 8. d 9. c 10. e.