GENERAL REPORTS ADNEXAL MALIGNANT TUMORS OF THE SKIN VIRGIL PÃTRAªCU, RODICA TASLÎCA, BIANCA ADELA CISMARU-IANCU Summary Adnexal malignant tumors are neoplasm originated in the adnexal skin structures (glands, hair follicles) and can develop on previously healthy skin, but usually they appear due to the malignization of different varieties of benign tumors. They represent a special chapter in oncological dermatology. These tumors are rare, well individualized, with a diagnosis sustained only on histopathological exam and immunohistochemistry. They have no distinctive clinical feature, which can make even an experimented phisician miss the diagnosis, after performing only a clinical exam. Adnexal malignant tumors are represented by: malignant tumors of the sebaceous glands; malignant tumors with appocrine and eccrine differentiation; malignant tumors with follicular differentiation. These groups include multiple entities, for each being presented the clinico-evolutive particularities, histopathological aspects, immunohistochimical and therapeutical conduit. Key words: adnexal carcinomas; histopathological exam; immunohistochimical investigations; treatment. Received: 7.7.2017 Accepted: 25.7.2017 Adnexal malignant tumors are types of that eliminate a coarse, yellow-grey material. neoplasms that have the origins in the adnexal This type of tumor, if present in Muir-Torre structures of the skin (glands, hair follicles) and syndrome, can be associated with other visceral they can develop on previously healthy skin. neoplasms. [4] Most frequently, they come from the The tumor evolution is local, infiltrative and malignization of previously benign tumors. [1,2] destructive, but it can also present in a metastasized form. Sebaceous carcinoma rarely I. Malignant tumors of the sebaceous metastasizes, with an incidence of 14% and this glands phenomenon occurs late in the evolution. [5,6] A particular aspect is represented by the Sebaceous adenocarcinoma (carcinoma of Meibomius glands adenocarcinoma, situated in the sebaceous glands) is a very rare tumor, with the eyelids, which represents the most frequent a frequency of 0,2% of the cutaneous carcino- localization of the sebaceous carcinomas. mas. They are mainly localized on the face Histopathologically, the tumors are made of (especially eyelids) and scalp. [3] cells with a morphology that resembles the one The clinical aspect is represented by a of the sebaceous glands, situated in the center of solitary nodular tumor, with smooth, translucid the tumoral lobules. The tumors also contain surface, pink or yellow-brown colored. The non-differentiated carcinomatous cells, situated tumor usually had 1 cm diameter, can be mostly at the periphery of the tumoral lobules. polylobate and can present ulcerations on the Immunohistochemistry shows an immune surface. On the section surface, the color is profile of the neoplastic cells resembling the cells yellow, sometimes sprinkled with small cysts within the benign sebaceous tumors (positive * Dermatology Department, University of Medicine and Pharmacy of Craiova, Romania. 33 DermatoVenerol. (Buc.), 62: 33-41 for high molecular weight cytokeratins, EMA, The tumor is positive for AE1/AE3, CK7 and C15/Leu M1). [7] Bcl-2, EMA and BerEP4. Alpha SMA and S100 are The treatment is represented by surgical positive in the tubular periphery. P53 is positive excision with safety margins, complete excision in less than 25% of the neoplastic cells. There is a before metastasis ensuring a high survival rate. proliferations index which is less than 5% [5,6] positive for Ki67 in the neoplastic cells, while CK20, C-erb and CD34 are negative. [1,2,8] II. Malignant tumors with apocrine and The treatment is surgical excision with oncological safety margins. Radiotherapy has eccrine differentiation rarely lead to success. In some cases, there has This type of tumor is more frequent than the been observed a slightly increased aggression of one developed from the adnexal structures of the the tumor after radiotherapy. [9] skin. This type contains the next entities: 2. Mixt malignant tumor (MMT) is an 1. Adnexal microcystic carcinoma (scleros- extremely rare skin adnexal tumor with an ing sweat duct carcinoma, eccrine epithelioma, aggressive local behavior and a high metastasis syringomatous carcinoma) is a well differentiated potential. Also known as mixt malignant apo- adenocarcinoma, with low metastasis capacity. crine tumor or malignant chondroid syringoma, [8] mixt malignant tumor is considered the Clinically, the tumor is located on the face, malignant correspondent for mixt benign tumors, usually affects adults, women more frequently although the histological diagnosis is based in the and has a slow growth, over a period of months first place in the biphasic character of the or even years. [9] neoplasia, rather than on a combination of benign tumoral debris with carcinomatous tissue. [1, 10] The classical histopathological aspect is This tumor can appear at any age (15 months- represented by solid or small cystic structures, 89 years) and is twice more frequent in women situated superficially, resembling the infundibu- than men. Compared to the corresponding lar ducts or cysts. In the central area, the tumor is benign form, the malignant one presents made of small ductal structures, with frequent predilection for the trunk and extremities, neural and perineural involvement. In the especially hands and feet. deepest areas where the tumor is infiltrated, the Clinically, most MMT are circumscripted and cells are arranged in “Indian line” within a may appear cystic, and in the moment of the sclerous stroma. This appearance gives the tumor medical examination, most of them are 2-15 cm a specific aspect of layered lesion: in the diameter. They are not painful or ulcerated and superficial area, it has a cystic and tubular aspect, have no distinctive clinical aspect. They rarely while the depths of the tumor are mainly made of have a rapid growth, with ulcerations or pain. cell cords and sclerosis. Sometimes it can present The section surface of the tumor can reveal a sebocytic areas, while other times it can present gelatinous material in variable quantity. Because with areas resembling the follicular sheath. This of the infiltrative growth, the tumor enucleation suggests that it can have differentiation towards is not possible. the follicular-sebaceous-apocrine unity. In some Histopathologically, MMT develops in the cases, the lesion is exclusively ductal, which has dermis and sub dermis and is presented as a determined some authors to call it syringo- large, asymmetrical tumor, poorly circum- matous carcinoma or sclerosing sweat duct scripted, biphasic, lobulated, with infiltrative carcinoma. [8,9] Some tumors present poro- margins and adjacent satellite tumoral nodules. matous or clear-cell aspects. Cytologically, the Rarely, the tumor can present juxtapositions of lesions are well differentiated, without nuclear benign and malignant areas. MMT is made of two pleiomorphism or mitotic figures. Actually, the components: epithelial and mesenchymal, the nuclear pleiomorphism must be taken in epithelial component is situated in the periphery, consideration when the microcystic carcinoma while the mesenchymal one is situated in the diagnosis is correct. center. The tumoral chondromyxoid stroma is 34 DermatoVenerol. (Buc.), 62: 33-41 PAS negative, being mainly made of hyaluronic carcinoma, squamous cell carcinoma or pyogenic acid and acid mucopolysaccharides. Rarely, the granuloma. The diagnosis is histopathological. stroma can turn to bone. The epithelial cellular [12,13] aggregates can present like confluent cords and Histopathologically, porocarcinoma forms cellular nests with variable shapes and sizes, nests and cords made of epithelial cells with pale mixed with tubular aspect areas. The tubular cytoplasm. Tumoral masses are well delimited, structures can be paved with at least two layers of frequently round, with polygonal cells that epithelial cells, the ones close to the lumenum are contain pleomorphic nuclei and irregular, similar to the cells with apocrine secretion, and prominent nucleoli and numerous mitotic the perilumenal ones, present plasmocytic or figures. These is a clear delimitation between the myoepithelial differentiation. [1,11] cellular nests and the adjacent epidermal The tumoral cells can present myoepithelial keratinocytes. The epidermis can be acanthotic. immunophenotype with expression for S100 and Both isolated cells and cellular nests can invade CK, including actine in some cells. Spindle cells the epidermis, in a pagetoid way. Keratinization from the area with myxoid stroma are positive for is usually absent. Intercellular bridges within the Vimentin. tumoral cells are invisible. Their connection with MMT proliferate in an invasive and destruc- the intraepidermal eccrine ducts can be observed, tive way, with a high local recurrence rate and but the intralimphatic invasion of the profound metastasis (over 50%) in local and regional lymph dermis can also be observed in 15% of the cases. nodes, lungs and bones. Death occurs in more The differential diagnosis includes: eccrine than 25% of the cases. Still, in over 30% of the poroma, hidroacanthoma simplex, Paget disease. cases, there is no recurrence or metastasis Eccrine poroma and hidroacanthoma simplex can (atypical mix skin tumor). Generally, MMT has a be atypical, but the lesions are symmetrical and prolonged evolution. Complete excision before well circumscripted. Porocarcinoma is