Poroma

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Poromas are benign tumors of the distal portion of sweat gland ducts. Skin.png
Poromas are benign tumors of the distal portion of sweat gland ducts.

Poromas are rare, benign, cutaneous adnexal tumors. [1] Cutaneous adnexal tumors are a group of skin tumors consisting of tissues that have differentiated (i.e. matured from stem cells) towards one or more of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. [2] Poromas are eccrine or apocrine sweat gland tumors derived from the cells in the terminal portion of these glands' ducts. [3] This part of the sweat gland duct is termed the acrosyringium and had led to grouping poromas in the acrospiroma class of skin tumors (syringofibroadenomas and syringoacanthomas are classified as acrospiromas). [3] [4] [5] [6] Here, poromas are regarded as distinct sweat gland tumors that differ from other sweat gland tumors by their characteristic clinical presentations, microscopic histopathology, and the genetic mutations that their neoplastic cells have recently been found to carry. [7]

Contents

As currently viewed, there are 4 poroma variants based on their predominant cell types and extent of their tumor tissues presence in the epidermis and dermis: 1) Hidroacanthoma simplex poromas are confined to the epidermis, i.e. uppermost layer of the skin. 2) Dermal duct poromas are confined to the dermis, i.e. layer of skin between the epidermis and subcutaneous tissues. [8] 3) Hidradenomas have recently been sub-classified into two groups; 95% are termed clear cell hidradenomas and have features suggesting that they derive from apocrine sweat glands while the remaining 5% are termed poroid hidradenomas and have features suggesting that they derive from eccrine sweat glands. [9] And 4) eccrine poromas are eccrine sweat gland tumors that consist of three cell types (see Histopathology section). [1] [3]

Poromas usually occur as single, small, skin tumors that develop in middle aged to elderly individuals. They may occur anywhere on the body, but are most commonly seen on the head, neck, and extremities. [3] They seldom cause symptoms. [8] While benign, long-standing poromas have, in very rare cases, progressed to malignant forms termed porocarcinomas. [8] Poromas are treated by excision; their removal is almost always curative. [3]

Presentation

Poromas are rare tumors that in two large review studies represented 0.0058% and 0.134% of all skin tumors; dermal duct tumors are the rarest form of the poromas, representing only 3.3% of these tumors in 3 studies examining 675 poroid neoplasms. [2] They usually occur in the elderly population (mean age 65.1–66.6 in different studies) as small (<2 centimeters), solitary dome-shaped papules, plaques, or nodules, that are skin-colored, pink, red, white, or blue and range from smooth to wart-like, ulcerative, [4] or pyogenic granuloma-like lesions. [10] They may be located on the palms of the hands, soles of the feet, trunk, face, neck, or other cutaneous surfaces [4] such as the areola, [11] nipple, [12] or other areas of the breast, [13] on the scrotum, [14] or on the vulva. [15] Rarely, individuals present with multiple poromas either in one or widespread areas; these cases are termed poromatosis. [3]

Poromas present more commonly in: pregnancy; [3] patients treated with electron therapy for mycosis fungoides; sites of chronic radiation dermatitis caused by long-term radiation exposure; [4] patients who received chemotherapy with or with radiation therapy (these patients have often presented with poromatosis); [16] individuals with underlying skin conditions such as hypohidrotic ectodermal dysplasia and Bowen’s disease (i.e. a form of squamous cell carcinoma that is localized to the outermost layer of the skin); and skin plaques of individuals with the congenital disease, nevus sebaceous. [3]

Poromas are usually slow growing and asymptomatic but some individuals report that their lesions are itchy, [4] mildly tender, or painful. [9] An existing poroma that develops spontaneous bleeding, ulceration, sudden itching, pain, or rapid growth over a short period of time may indicate that it has become a cancerous porocarcinoma. [4] These cancers may metastasize to local lymph nodes, nearby or distal skin sites, bones, bladder, breast, retroperitoneum, ovary, liver, lung, [17] brain, or stomach. However, the progression of a poroma to a porocarcinoma is very rare, [18] i.e. less than 1% of cases. [9]

Histopathology

Dermoscopy and histopathology of eccrine poroma: (A) Clinical presentation of a nonpigmented eccrine poroma sensu stricto as a pink nodule located on the foot (B,C) Dermoscopy shows milky red areas (light blue arrow), milky red globules (dark blue triangle), and dotted vessels (black arrow) (original magnifications x20 and x40, respectively). (D,E) Histopathologically, the neoplasm consists of poroid and cuticular cells and tubular structures that are continuous with the epidermis (H&E stain, original magnifications x10 and x40, respectively). Dermoscopy and histopathology of eccrine poroma.jpg
Dermoscopy and histopathology of eccrine poroma: (A) Clinical presentation of a nonpigmented eccrine poroma sensu stricto as a pink nodule located on the foot (B,C) Dermoscopy shows milky red areas (light blue arrow), milky red globules (dark blue triangle), and dotted vessels (black arrow) (original magnifications ×20 and ×40, respectively). (D,E) Histopathologically, the neoplasm consists of poroid and cuticular cells and tubular structures that are continuous with the epidermis (H&E stain, original magnifications ×10 and ×40, respectively).

Microscopic histopathological examinations of the tumor tissues of all poroma variants stained with hematoxylin and eosin dyes reveal: a) basophilic "poroid cells" (i.e. small, cuboid-shaped cells with oval nuclei which resemble cells in the peripheral layer of the distal portion of eccrine sweat gland ducts [20] ) that may form cords and broad columns extending downward from the epidermis; b) larger cuticular cells (i.e. squamous epithelial-like eosinophilic cells that resemble the luminal cells lining eccrine sweat gland ducts [20] ); and in some cases c) clear cells (i.e. cells with small nuclei surrounded by pale cytoplasm). [3] Poroma tumor tissues may appear highly vascularized and/or have areas of necrosis, i.e. dead or dying cells. Hidroacanthoma simplex variants are mainly composed of poroid cells, few cuticular cells, and no clear cells and are confined to the epidermis; dermal ductal variants are mostly confined to the superficial dermis and are composed of small solid and cystic nodular aggregates of poroid, cuticular, and clear cells; poroid hidradenoma variants have large aggregates of solid and cystic components and extend deeper into the dermis or even subcutis; and eccrine poroma variants are composed of all three cell types but are primarily located in the epidermis and superficial dermis. Poromas may have 2 or more of these variants in the same tumor tissue and the variants typically have histopathology findings that are not clearly distinguishable from each other. [3]

Immunohistochemistry

As detected by immunohistochemical analyses, the poroma tumor cells, regardless of variant type, test positive when probed with the AE1/AE3 antibody cocktail that detects various cytokeratin proteins. Tumor cells of the four variants also commonly express carcinoembryonic antigen (i.e. CEA) or MUC1 (also termed EMA) and, except for the hidroacanthoma simplex variant, the carcinoembryonic antigen and MUC1 protein. [7]

Gene abnormalities

The four poroma variants contain at least one of two YAP1 fusion genes, i.e. abnormal genes caused by a mutation which merges a part of the YAP1 gene fused to part of either the Nuclear protein in testis gene (also termed the NUTM1 gene) or the MAML2 gene to form the YAP1::NUTM1 and YAP::MAML2 fusion genes, respectively. [3] Rarely, they may also contain a WWTR1::NUTM1 fusion gene. The YAP1::MAML2 fusion gene is detected in ~63% of poromas, the YAP1::NUTM1 fusion in 20.2% to 66% of poromas, and the WWTR1::NUTM1 fusion gene in 1% of poromas. [1] YAP1 [21] and WNTR1 [22] fusion genes have been implicated in the initiation, aggressiveness, metastasis, and/or therapy resistance of various neoplasms. Studies are needed to determine if they play a role in the development and/or progression of poromas.

Diagnosis

The great diversity, rarity, and complex terminology of poromas make their diagnosis challenging. They have been misdiagnosed as other types of skin tumors including porocarcinomas, basal cell carcinomas, pyogenic granulomas, skin tags, plantar warts (i.e. warts on the palms or soles), fibromas, hemangiomas, pigmented moles, seborrheic keratosis, trichilemmomas, melanomas, Kaposi sarcomas, and other adnexal tumors. Poromas are typically diagnosed based on their clinical presentation; microscopic histopathology showing tumor tissues consisting of poroid, cuticular, and/or clear cells; and, in unclear cases, the presence of tumor cells that express a YAP1::NUTM1, YAP::MAML2, and/or WWTR1::NUTM1 fusion gene. [3] [7] However, these fusion genes also occur in porocarcinomas and cannot be used to differentiate poromas from their malignant counterpart. Poromas and porocarcinomas are distinguished based on their clinical findings and histopathology, e.g. a higher Ki67 labeling index and aberrant expression of p53, RB, and p16 proteins are more frequent in porocarcinoma (see Diagnosis of porcarcinomas). [7] Dermatoscopy, particularly when revealing a "leaf- and flower-like pattern" in a skin tumor, has been used as a strong indicator that the lesion is a poroma, but confirmation of this diagnosis ultimately relies on histopathological analyses. [3]

There is no clear-cut evidence that diagnosing a poroma's variant type carries any clinical or therapeutic significance. [3]

Treatment

Superficial poroma tumors have been treated by shaving (i.e. removal using a sharp razor) or electrosurgical destruction. [3] Deeper lesions have been removed by excisional biopsy (i.e. a procedure in which an entire tumorous or suspicious area is removed) [23] or simple surgical excision. [3] Since poromas are almost always benign tumors and rarely recur after their removal, [4] these treatments are in general curative. [3]

See also

Related Research Articles

<span class="mw-page-title-main">Skin</span> Soft outer covering organ of vertebrates

Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.

<span class="mw-page-title-main">Perspiration</span> Fluid secreted from sudoriferous glands

Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals.

<span class="mw-page-title-main">Apocrine</span>

Apocrine is a term used to classify the mode of secretion of exocrine glands. In apocrine secretion, secretory cells accumulate material at their apical ends, and this material then buds off from the cells, forming extracellular vesicles. The secretory cells therefore lose part of their cytoplasm in the process of secretion.

<span class="mw-page-title-main">Skin condition</span> Any medical condition that affects the integumentary system

A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment.

<span class="mw-page-title-main">Sweat gland</span> Small sweat-producing tubular skin structures

Sweat glands, also known as sudoriferous or sudoriparous glands, from Latin sudor 'sweat', are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial surface by way of a duct. There are two main types of sweat glands that differ in their structure, function, secretory product, mechanism of excretion, anatomic distribution, and distribution across species:

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

Hidradenoma refers to a benign adnexal tumor of the apical sweat gland. These are 1–3 cm translucent blue cystic nodules. It usually presents as a single, small skin-colored lesion, and may be considered closely related to or a variant of poromas. Hidradenomas are often sub-classified based on subtle histologic differences, for example:

An apocrine sweat gland is composed of a coiled secretory portion located at the junction of the dermis and subcutaneous fat, from which a straight portion inserts and secretes into the infundibular portion of the hair follicle. In humans, apocrine sweat glands are found only in certain locations of the body: the axillae (armpits), areola and nipples of the breast, ear canal, eyelids, wings of the nostril, perineal region, and some parts of the external genitalia. Modified apocrine glands include the ciliary glands in the eyelids; the ceruminous glands, which produce ear wax; and the mammary glands, which produce milk. The rest of the body is covered by eccrine sweat glands.

<span class="mw-page-title-main">Eccrine sweat gland</span> Sweat gland distributed almost all over the human body

Eccrine sweat glands are the major sweat glands of the human body. Eccrine sweat glands are found in virtually all skin, with the highest density in the palms of the hands, and soles of the feet, and on the head, but much less on the torso and the extremities. In other mammals, they are relatively sparse, being found mainly on hairless areas such as foot pads. They reach their peak of development in humans, where they may number 200–400/cm2 of skin surface. They produce sweat, a merocrine secretion which is clear, odorless substance, consisting primarily of water. These are present from birth. Their secretory part is present deep inside the dermis.

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

A papillary hidradenoma, also termed hidradenoma papilliferum or mammary-like gland adenoma of the vulva, is a rare, but nonetheless most common benign tumor that occurs in and between anal and genital regions of females. These hidradenomas are sharply circumscribed, nodular tumors that usually develop in women's anogenital area but uncommonly occur in other sites in women and men. Papillary hidradenomas that develop outside of the anogenital region are termed ecctopic papillary hidradenomas or ectopic hidradenoma papilliferums.

<span class="mw-page-title-main">MAML2</span> Protein-coding gene in the species Homo sapiens

Mastermind-like protein 2 is a protein that in humans is encoded by the MAML2 gene.

Eccrine angiomatous hamartoma (EAH), first described by Lotzbeck in 1859, is a rare benign vascular hamartoma characterized histologically by a proliferation of eccrine and vascular components. EAH exists on a spectrum of cutaneous tumors that include eccrine nevus, mucinous eccrine nevus and EAH. Each diagnostic subtype is characterized by an increase in the number as well as size of mature eccrine glands or ducts, with EAH being distinguished by the added vascular component.

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

Syringocystadenoma papilliferum is a rare non-malignant adnexal neoplasm that develops from apocrine or eccrine sweat glands and can be identified histologically by cystic, papillary, and ductal invaginations into the dermis lined by double-layered outer cuboidal and luminal high columnar epithelium and connected to the epidermis.

Porocarcinoma (PCA) is a rare form of skin cancer that develops in eccrine sweat glands, i.e. the body's widely distributed major type of sweat glands, as opposed to the apocrine sweat glands which are located primarily in the armpits and perineal area. This cancer typically develops in individuals as a single cutaneous tumor in the intraepidermal spiral part of these sweat glands' ducts at or near to where they open on the skin's surface. PCA tumors are classified as one form of the cutaneous adnexal tumors; in a study of 2,205 cases, PCA was the most common (11.8%) form of these tumors.

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

Spiradenomas (SA) are rare, benign cutaneous adnexal tumors that may progress to become their malignant counterparts, i.e. spiradenocarcinomas (SAC). Cutaneous adnexal tumors are a group of skin tumors consisting of tissues that have differentiated towards one of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. SA and SAC tumors were regarded as eccrine gland tumors and termed eccrine spiradenomas and eccrine spiradenocarcinomas, respectively. However, more recent studies have found them to be hair follicle tumors and commonly term them spiradenomas and spiradenocarcinomas, respectively. Further confusing the situation, SA-like and SAC-like tumors are also 1) manifestations of the inherited disorder, CYLD cutaneous syndrome (CCS), and 2) have repeatedly been confused with an entirely different tumor, adenoid cystic carcinomas of the salivary gland. Here, SA and SAC are strictly defined as sporadic hair follicle tumors that do not include the hereditary CCS spiradenomas and heridtary spiradenocarcinoms of CCS or the adenoid cystic carcinomas.

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

Eccrine carcinoma is a rare skin condition characterized by a plaque or nodule on the scalp, trunk, or extremities. It originates from the eccrine sweat glands of the skin, accounting for less than 0.01% of diagnosed cutaneous malignancies. Eccrine carcinoma tumors are locally aggressive, with a high rate of recurrence. Lack of reliable immunohistochemical markers and similarity to other common tumors has made identification of eccrine carcinoma difficult.

<span class="mw-page-title-main">Hidradenocarcinoma</span>

Hidradenocarcinoma is a malignant adnexal tumor of the sweat gland. It is the malignant variant of the benign hidradenoma. It may develop de novo or in association with an existent hidradenoma.

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

Acrospiromas are a broad class of benign cutaneous adnexal tumors. Cutaneous adnexal tumors are a group of skin tumors consisting of tissues that have differentiated towards one or more of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. Acrospiromas are thought to derive from apocrine or eccrine sweat gland ducts near their acrosyringium, i.e. point where these ducts open to the skin's surface.

The nuclear protein in testis gene encodes a 1,132-amino acid protein termed NUT that is expressed almost exclusively in the testes, ovaries, and ciliary ganglion. NUT protein facilitates the acetylation of chromatin by histone acetyltransferase EP300 in testicular spermatids. This acetylation is a form of chromatin remodeling which compacts spermatid chromatin, a critical step required for the normal conduct of spermatogenesis, i.e. the maturation of spermatids into sperm. Male mice that lacked the mouse Nutm1 gene using a gene knockout method had abnormally small testes, lacked sperm in their cauda epididymis, and were completely sterile. These findings indicate that Nutm1 gene is essential for the development of normal fertility in male mice and suggest that the NUTM1 gene may play a similar role in men.

CYLD cutaneous syndrome (CCS) is the recently designated term for three rare inherited cutaneous adnexal tumor syndromes: multiple familial trichoepithelioma (MFT1), Brooke–Spiegler syndrome (BSS), and familial cylindromatosis (FC). Cutaneous adnexal tumors are a large group of skin tumors that consist of tissues that have differentiated towards one of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. CCS tumors are hair follicle tumors.

<span class="mw-page-title-main">Pure apocrine carcinoma of the breast</span> Medical condition

Pure apocrine carcinoma of the breast (PACB) is a rare carcinoma derived from the epithelial cells in the lactiferous ducts of the mammary gland. The mammary gland is an apocrine gland. Its lactiferous ducts have two layers of epithelial cells, a luminal layer which faces the duct's lumen and a basal layer which lies beneath the luminal layer. There are at least 4 subtypes of epithelial cells in these ducts: luminal progenitor cells and luminal mature cells which reside in the luminal layer and mammary stem cells and basal cells which reside in the basal layer. Examination of the genes expressed in PACB cancer cells indicate that most of these tumors consist of cells derived from luminal cells but a minority of these tumors consist of cells derived from basal cells.

References

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