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Background

This rare skin cancer is important to diagnose because of the very aggressive behavior it typically exhibits. For reasons which are unclear, the tumor tends to occur on the left side of the face. Clinically, these tumors are often misdiagnosed as basal cell carcinomas, squamous cell carcinoma, or scar. Histologically, these tumors are often misdiagnosed as syringomas, basal cell carcinomas, or a benign adnexal neoplasm.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/
Other Diagnostic Testing
 
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
RADIATION THERAPY
J Oral Maxillofac Surg 1995;53:846-849
J Am Acad Dermatol 1999;41:225-231

Microcystic adnexal carcinoma arising in the setting of previous radiation therapy.

Antley CA, Carney M, Smoller BR.

Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, USA.

J Cutan Pathol 1999 Jan;26(1):48-50 Abstract quote

While there are several reports of microcystic adnexal carcinoma developing in patients within sites of previous therapeutic irradiation, this relationship is not well described in the dermatologic literature.

We report a case of a 42-year-old man with a remote history of therapeutic irradiation following surgical resection of periorbital rhabdomyosarcoma. Subsequently, he developed multiple basal cell carcinomas and a microcystic adnexal carcinoma within the field of irradiation.

The histologic features were those of a classic microcystic adnexal carcinoma, with well differentiated nests and cords of keratinocytes displaying follicular and ductular differentiation infiltrating diffusely into the reticular dermis. Dense fibrosis was present surrounding the neoplastic keratinocytes. Nuclear atypia and mitotic figures were not identified. A carcinoembryonic antigen (CEA) stain demonstrated glandular differentiation.

It is important for dermatologists to be aware of the apparent relationship between the rare microcystic adnexal carcinoma with its innocuous scar-like clinical appearance and prior local radiation therapy.

Chronic sun exposure
Ear Nose Throat J 1991;70:789-793
SYNONYMS Sclerosing sweat duct carcinoma
INCIDENCE Rare
AGE RANGE-MEDIAN 19-90 years
Median 65 years
SEX (M:F)
Slight female predominance
RACE  
AFRICAN-AMERICAN  

Microcystic adnexal carcinoma: First reported case in an African American man

Christopher M. Peterson, MD John L. Ratz, MD Omar P. Sangueza, MD

Augusta, Georgia

J Am Acad Dermatol 2001;45:283-5 Abstract quote

Microcystic adnexal carcinoma (MAC) is a relatively uncommon adnexal neoplasm that can display aggressive local invasion. MAC occurs most commonly on the central part of the face and can be clinically asymptomatic with a benign appearance. We describe the first reported case of MAC in an African American man who was treated by Mohs micrographic surgery.

Neglected microcystic adnexal carcinoma: the second reported case in a black patient.

Gardner ES, Goldberg LH.

DermSurgery Associates, P.A., Houston, Texas 77030, USA.

Dermatol Surg 2001 Jul;27(7):678-80 Abstract quote

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a histologically aggressive appendageal neoplasm that often pursues a beguilingly indolent clinical course. MAC has previously been reported only once in a black patient.

OBJECTIVE: To present the second MAC ever recorded in a black patient.

METHODS: We describe a MAC of substantial dimension occurring in a black patient. The literature was subsequently examined for MAC occurring in ethnic patients.

RESULTS: This MAC is remarkable not only for its occurrence in a black patient, but also because it is one of the largest MACs ever recorded (8 cm), it occurs in a relatively less common site (scalp), and its latency period before diagnosis is the longest ever definitively documented (31 years).

CONCLUSION: MAC is rare among non-Caucasians. Its relatively indolent clinical growth, especially in sites that are poorly accessible to patient observation, may lead to significant delay in diagnosis and treatment.

 

DISEASE ASSOCIATIONS CHARACTERIZATION
IMMUNOCOMPROMISED STATES  
Immunodeficiency with immunosuppresion and kidney transplantation Br J Ophthalmol 1995;113:1332-1333
After chemotherapy for breast cancer Laryngoscope 1995;105:1197-1201
After chemotherapy for acute T-cell lymphoblastic leukemia J Am Acad Dermatol 1999;41:225-231
After chemotherapy for liposarcoma Am J Dermatopathol 1997;19:358-362

Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma.

Lei JY, Wang Y, Jaffe ES, Turner ML, Raffeld M, Sorbara L, Morris J, Holland SM, Duray PH.

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Am J Dermatopathol 2000 Dec;22(6):524-9 Abstract quote

Cutaneous microcystic adnexal carcinoma (MAC) is a rare and poorly understood tumor that predominantly occurs in the head and neck. MAC usually affects people in their fourth and fifth decades. Some patients have had a history of radiation.

We present a case of MAC occurring in the left antecubital fossa of an 18-year-old white woman with an unusual immunodeficiency syndrome. The patient also developed a squamous cell carcinoma, a cutaneous T-cell malignancy, and a perigastric leiomyoma. A congenital infection of herpes simplex virus (HSV) persisted throughout her life.

The association of HSV infection with MAC and squamous cell carcinoma and that of peripheral T-cell lymphoma with Epstein-Barr virus is discussed in relation to her immunodeficiency.

 

PATHOGENESIS CHARACTERIZATION
ADNEXAL ORIGIN Speculation that the tumor has mixed adnexal lineage with eccrine, follicular, and apocrine features
CHROMOSMAL ABNORMALITIES  

Cytogenetic and fluorescence in situ hybridization analyses of a microcystic adnexal carcinoma with del(6)(q23q25).

Wohlfahrt C, Ternesten A, Sahlin P, Islam Q, Stenman G.

Department of Pathology, Goteborg University, Gothenburg, Sweden.

Cancer Genet Cytogenet 1997 Oct 15;98(2):106-10 Abstract quote

Cytogenetic analysis of a case of microcystic adnexal carcinoma (MAC) revealed three unrelated clones with the karyotypes: 46,XX,del(6)(q23q25)[17]/46,XX,1 approximately 2dmin[4]/46,XX,t(1;3) (p10;q10)[2].

Analysis of the 6q- by fluorescence in situ hybridization (FISH) showed that it had resulted from a long arm deletion. The finding of a clonal 6q deletion as the sole karyotypic change in a MAC is of special interest because we previously have identified 6q deletions in different types of malignant salivary gland tumors.

This observation, together with the histopathologic similarities between salivary gland tumors and sweat gland tumors, further emphasize the histogenetic relationships between these tumor types.

STROMAL GROWTH  

Microcystic adnexal carcinoma: in vitro growth characteristics and effect on stromal collagen production.

Moy RL, Tahery DP, Howe K.

UCLA Division of Dermatology 90024-6957.

Int J Dermatol 1993 May;32(5):341-4 Abstract quote

BACKGROUND. Microcystic adnexal carcinoma (MAC) is a locally aggressive cutaneous neoplasm, which is characterized by follicular and sweat gland differentiation and a stroma of dense collagen.

METHODS. MAC cells were studied and characterized in vitro through phase microscopy and proliferation assays. Additionally, to delineate a possible role of soluble mediators in bringing about the dense stromal collagen seen in association with these tumors, the effect of conditioned media derived from the tumor cells on the level of collagen production by normal fibroblasts was examined.

RESULTS. A significant morphologic difference between the MAC cells and normal keratinocytes was not noted. Proliferation assays demonstrated a significantly slower rate of growth of the MAC cells in comparison to controls. Media conditioned by MAC cells did not induce an increase in collagen synthesis by cultured fibroblasts, but rather, there appeared to be an inhibitory effect on the level of collagen synthesis.

CONCLUSIONS. The increased stromal collagen seen in MAC histologically is not the result of growth factors or cytokines produced by the MAC cells.

 

CLINICAL VARIANTS CHARACTERIZATION
BONE AND MARROW INVASION  

Microcystic adnexal carcinoma with mandibular invasion and bone marrow replacement.

Birkby CS, Argenyi ZB, Whitaker DC.

Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City 52242.

J Dermatol Surg Oncol 1989 Mar;15(3):308-12 Abstract quote

A 51-year-old man with microcystic adnexal carcinoma of the face is reported. In addition to extensive soft tissue invasion by the cancer, there was direct bone invasion into the marrow of the mandible as well as perineural spread along the mental and inferior alveolar nerves.

This represents the first case of microcystic adnexal carcinoma with documented bone invasion. Recognition of the aggressive nature of this cancer with potential for invasion into the skull is important for proper evaluation and treatment.

CHILDHOOD  
Occurring in an 11 year old boy
J Dermatol Surg Oncol 1994;20:767-768
GENITAL SKIN  
Occurring in genital skin
Arch Dermatol 2000;136:1355-1359
VULVA  

Microcystic adnexal carcinoma of the vulva.

Buhl A, Landow S, Lee YC, Holcomb K, Heilman E, Abulafia O.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, State University of New York Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, New York, 11203, USA.

Gynecol Oncol 2001 Sep;82(3):571-4 Abstract quote

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a subset of sweat gland carcinoma first described as a specific entity by D. J. Goldstein, R. J. Barr, and D. J. Santa Cruz (Cancer 1982;50:566-72). We report the first case of MAC occurring on the vulva and review the literature pertaining to this rare tumor.

CASE: A 43-year-old multiparous black woman presented initially to Kings County Hospital Medical Center with a chief complaint of a vulvar lesion arising on the left labia majora which she had noted for 4 years prior to presentation. Aside from increasing paresthesia in the area, she denied any constitutional symptoms. Her past medical history was significant only for hyperthyroidism and mild hypertension and surgical history was noncontributory. Gynecologic history was unremarkable, with sporadic care over the last 20 years. Physical examination revealed a 1.5 x 2.0-cm raised, well-circumscribed, firm mobile lesion on the left labia majora. It was noted to be yellow in color with the surrounding tissue being unremarkable in character. The remainder of her gynecologic examination and lymph node survey was unremarkable. Preoperative chest X ray was negative as was the CAT scan of the abdomen and pelvis. All laboratory values were within normal limits. A Pap smear done preoperatively was significant for atypical squamous and glandular cells of undetermined significance. Subsequent colposcopic examination of the cervix was remarkable for cervicitis and was adequate, with the entire transformation zone visualized. Both endocervical curettage and endometrial biopsy were normal. Initially, an excisional biopsy was performed with final pathology demonstrating microcystic adnexal carcinoma with positive surgical margins. She subsequently underwent a left radical hemivulvectomy with bilateral inguinal groin lymph node dissection. At the time of surgery, the left labia majora was noted to be well healed, with a residual surgical scar easily discernible. No areas of discoloration were noted and digital palpation of the area was unremarkable. Microscopic residual tumor was noted; however, all surgical margins and lymph nodes were negative for tumor. Her postoperative course was unremarkable. The patient has continued to do well since the time of her surgery and is being followed conservatively.

CONCLUSION: Radical vulvectomy should be performed when MAC occurs in the vulva to secure negative margins of resection. Groin dissection should be reserved for cases in which the inguinal lymph nodes are clinically suspicious or in cases of tumor recurrence.

 

HISTOLOGICAL TYPES CHARACTERIZATION
General

Nests of uniform, cuboidal and flattened squamoid cells in a dense collagenized stroma

Microcysts with keratinaceous material

Solid nests with comma-shaped tails resembling syringoma

Tubuloalveolar structures with one to two layers of cuboidal cells

Deep infiltration into subQ fat, skeletal muscle, and perineural invasion

Microcystic adnexal carcinoma: a distinct clinicopathologic entity.

Goldstein DJ, Barr RJ, Santa Cruz DJ.

Cancer 1982 Aug 1;50(3):566-72 Abstract quote

Microcystic adnexal carcinoma is an unusual locally aggressive neoplasm that is important to recognize since it may be confused with benign adnexal neoplasms, particularly desmoplastic trichoepithelioma, trichoadenoma, and syringoma.

Six cases are described all of which displayed benign histological features on initial biopsy. Most often these neoplasms presented as solitary flesh-colored indurated plaques on the upper lip. All patients were white, five were women, and the average age was 44-years-old.

Islands of basaloid keratinocytes, some of which contained horn cysts and abortive follicles, were embedded in a desmoplastic stroma. In other foci, ducts and gland-like structures lined by a two-cell layer predominated. In deep components individual and thin strands of cells dissected collagen bundles and skeletal muscle and invaded perineural spaces. Despite this, cytologic atypia and mitotic figures were rare.

The cell of origin is considered to be a pluripotential adnexal keratinocyte which is capable of both follicular and sweat gland differentiation.

Microcystic adnexal carcinoma: a light microscopic, immunohistochemical and ultrastructural study.

\Kato H, Mizuno N, Nakagawa K, Furukawa M, Hamada T.

Department of Dermatology, Osaka City University Medical School, Japan.

J Cutan Pathol 1990 Apr;17(2):87-95 Abstract quote

We report a case of microcystic adnexal carcinoma (MAC) occurring on the upper lip of an 82-year-old woman.

Microscopically the tumor showed both pilar and sweat gland differentiation, involved the entire dermis and subcutaneous tissue, and invaded perineural spaces. Immunoperoxidase studies revealed carcinoembryonic antigen to be present in the ductal lining cells and in the amorphous content in the lumen, confirming sweat gland differentiation.

The S-100 protein was positive in dendritic cells within the solid cell nests, but negative in cells lining cystic spaces. Ultrastructural study confirmed that the neoplasm was composed of two components, with pilar and eccrine differentiation. The former showed concentric layers of squamous epithelial cells with well-developed desmosomes and cytofilaments. The latter had ductal and alveolar structures; the ultrastructural features included: i) numerous villous folds of plasma membrane to interdigitate each other by focal desmosomes, ii) aggregates of cytofilaments, and iii) basally located myoepithelial cells which were separated from the surrounding stroma by rather thick basement membrane. In addition, distinct amyloid deposition was also observed on ultrastructural examination.

To our knowledge, amyloid deposition has not been previously reported in MAC.

 

Am J Dermatopathol 1997;19:35862.

Type 1 Pilar
Type 1a
Pilar exclusively
Type 1b
Pilar with sodoriparous
Type 1c
Sebaceous-pilar +/- sudoriparous
Type 2 Purely sudoriparous
VARIANTS  
HIGH GRADE HISTOLOGIC CHANGES  
High (nuclear) grade adnexal carcinoma with microcystic adnexal carcinoma-like structural features.

Department of Pathology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.

Am J Dermatopathol. 2006 Aug;28(4):346-51 Abstract quote

Microcystic adnexal carcinoma (MAC) is a slow growing, locally aggressive sweat gland tumor. It predominantly affects the face and tends to recur despite local excision. Microscopically, MAC is characterized by a stratified proliferation of microcysts, cords, and ducts of cells that show squamous or adnexal differentiation. Atypia and mitoses are almost completely absent and metastatic deposits are rare and mostly limited to the regional lymph nodes; rather than real metastases, they might be the result of local extension of the tumor through perineurial spaces.

We report a case of adnexal carcinoma with architectural features of MAC that displayed also marked nuclear pleomorphism and hyperchromasia with squamous pearl formation and a widespread strong p53 immunoreaction. The lesion behaved as a high-grade neoplasm with rapid growth, carcinosarcomatous metaplastic transformation in a relapse, and what were clinically suspected to be metastases. The literature contains several other examples reported as metastatic high-grade MAC, one of them with widespread distant metastases.

We therefore want to sound an alert about the possible existence of tumors displaying microscopic findings characteristic of the aggressive forms of sweat gland carcinoma (nuclear pleomorphism and hyperchromasia, vascular invasion, and necrosis) in addition to architectural features of MAC. Whether these tumors should be called high-grade MACs or belong to a separate category remains an open issue until more cases are reported and bridge cases are eventually documented.
SEBACEOUS DIFFERENTIATION  

Microcystic adnexal carcinoma with extensive sebaceous differentiation.

Pujol RM, LeBoit PE, Su WP.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Am J Dermatopathol 1997 Aug;19(4):358-62 Abstract quote

We report two cases of microcystic adnexal carcinoma showing extensive sebaceous differentiation.

Multiple cellular nests and strands within a moderately sclerotic stroma involving the full thickness of the dermis were observed. Clusters of basaloid cells with extensive sebaceous differentiation were present. Foci of sebaceous ductal differentiation were observed in the more superficial areas. Neither strikingly atypical cells nor mitotic figures were present. Perineural invasion was present in the deep areas of both tumors.

Clinically, the lesions were solitary whitish-pink papules with a central dell on the faces of 2 men (aged 78 and 73 years old).

We propose a relationship between these tumors and other cytologically bland but locally aggressive adnexal carcinomas. Sebaceous differentiation itself in a poorly circumscribed neoplasm does not indicate conventional extraocular sebaceous carcinoma. We propose a simple classification of locally aggressive adnexal carcinomas that takes into account the full range of adnexal differentiation that can occur in such lesions.

 

SPECIAL STAINS/
IMMUNO-
PEROXIDASE
CHARACTERIZATION
Immunoperoxidase  
Microcystic adnexal carcinoma: an immunohistochemical reappraisal.

1Department of Pathology, UMass Medical School, Worcester, MA, USA.

 

Mod Pathol. 2008 Feb;21(2):178-85. Abstract quote

Even though immunohistochemical comparisons of microcystic adnexal carcinoma vs infiltrative basal cell carcinoma and desmoplastic trichoepithelioma exist, they are mostly restricted to the use of a single stain. In addition, a comparison with squamous cell carcinoma has not been reported previously. In this study, we compare the expression of cytokeratin (CK) 15, CK7, CK20, CK903, carcinoembryonic antigen (CEA), CD10, CD15 and BerEP4 in 13 microcystic adnexal carcinoma, eight desmoplastic trichoepithelioma, 10 infiltrative basal cell carcinoma, and eight squamous cell carcinoma of which five exhibited ductal differentiation.

We found that the majority of microcystic adnexal carcinoma (92%) and desmoplastic trichoepithelioma (100%) cases expressed CK15 while the infiltrative basal cell carcinoma and squamous cell carcinoma cases were all negative. Forty percent of infiltrative basal cell carcinoma expressed CK7; while only two microcystic adnexal carcinoma cases (15%) and one squamous cell carcinoma with ductal differentiation (12%) expressed CK7 in the remaining three tumor categories. None of the desmoplastic trichoepithelioma expressed CK7. All tumors were strongly positive for CK903. While the neoplastic cells were negative, luminal staining of ductal structures was noted for CK7, CD15 and CEA in some of the microcystic adnexal carcinoma, desmoplastic trichoepithelioma and squamous cell carcinoma with ductal differentiation cases. Sixty percent of infiltrative basal cell carcinoma, 31% of microcystic adnexal carcinoma, and 25% of squamous cell carcinoma express CD10. BerEP4 expression was noted in 38% of microcystic adnexal carcinoma, 57% of desmoplastic trichoepithelioma, 100% of infiltrative basal cell carcinoma, and 38% of squamous cell carcinoma. In conclusion, we found CK15 to be a useful marker in distinguishing microcystic adnexal carcinoma from infiltrative basal cell carcinoma and squamous cell carcinoma with ductal differentiation.

Our experience indicates that microcystic adnexal carcinoma and desmoplastic trichoepithelioma have a similar immunohistochemical profile that is, CK15+ and BerEP4+/-; thus, additional studies are needed to separate these two entities.

Microcystic adnexal carcinoma. An immunohistochemical comparison with other cutaneous appendage tumors.

Wick MR, Cooper PH, Swanson PE, Kaye VN, Sun TT.

Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis.

Arch Dermatol 1990 Feb;126(2):189-94 Abstract quote

Since its initial description, microcystic adnexal carcinoma (MAC) of the skin has been controversial. In particular, it features keratin production of the type seen in some pilar neoplasms , and has been thought to pursue partial follicular differentiation. Diagnostically, MAC may be difficult to separate from desmoplastic trichoepithelioma (DTE) in superficial biopsy specimens.

We studied 12 MACs, 22 malignant eccrine acrospiromas, 7 sudoriferous syringometaplasias, 6 syringomas, 5 DTEs, and 40 other benign pilar neoplasms immunohistochemically. Paraffin sections and antibodies to "hard" (pilar) keratins. epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Leu-M1, and S100 protein were employed.

The MACs exhibited reactivity for hard keratin subclasses AE 13 and AE 14, EMA, CEA, and Leu-M1. Desmoplastic trichoepitheliomas expressed positivity for AE 14, EMA, and Leu-M1 focally, but lacked the other specified markers. Syringomas and malignant acrospiromas displayed EMA, CEA, and AE 14 reactivity, and 5 syringometaplastic lesions were AE 14-reactive. Benign pilar tumors aside from DTEs were reactive only for AE 13, AE 14, or both.

These data indicate that MAC exhibits an immunophenotype that is a "hybrid" of those seen in pure sweat glandular and follicular neoplasms, and suggest that it may indeed show combined pilar and sudoriferous differentiation. Based on these results, it also appears that immunohistochemical analysis may be useful in the diagnostic separation of MAC and DTE.

Microcystic adnexal carcinoma of the skin. A reappraisal of the differentiation and differential diagnosis of an underrecognized neoplasm.

LeBoit PE, Sexton M.

Department of Pathology, University of California at San Francisco, School of Medicine 94143-0506.

J Am Acad Dermatol 1993 Oct;29(4):609-18 Abstract quote

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a locally aggressive adnexal neoplasm whose histogenesis is disputed. Many cases referred to us had been misdiagnosed.

OBJECTIVE: Our purpose was to clarify the differential diagnosis and differentiation of MAC.

METHODS: We sought follow-up data and examined routinely stained sections from 17 cases. We performed immunoperoxidase stains for carcinoembryonic antigen, pilar keratin (AE13), proliferating cell nuclear antigen (PCNA), type IV collagen, p53, and CD34 on selected cases.

RESULTS: Nine biopsy specimens had initially been misinterpreted. Cysts containing compact keratin or shadow cells were present in 11 cases, which we interpret as evidence of follicular differentiation. Sebaceous gland and duct as well as inner root sheath structures were seen in one case each. CD34 did not mark the clear cells as it does those of the outer root sheath. Staining for PCNA, type IV collagen, and p53 did not distinguish MAC from benign adnexal neoplasms.

CONCLUSION: MAC can be distinguished from its simulants in adequate biopsy specimens. Incompletely excised lesions usually recur. Both follicular and sudoriforous differentiation is present. Type IV collagen, PCNA, and p53 antisera were not useful in differential diagnosis.

Microcystic Adnexal Carcinoma An Immunohistochemical Study Including Markers of Proliferation and Apoptosis

Kathleen J. Smith, etal.

Am J Surg Pathol 2001;25:464-471 Abstract quote

Microcystic adnexal carcinoma (MAC) is the prototype for a subset of locally aggressive adnexal carcinomas (LAACs). Ultraviolet radiation (UVR) and UVB signature p53 mutations are implicated in the etiology of the most common cutaneous carcinomas. However in MACs, the role of UVR and p53 mutations is unknown. In addition, controversy still exists regarding the patterns of differentiation within these tumors.

The objective of this study was to determine the expression patterns of immunohistochemical markers for p53, Ki-67, c-erbB-2, and Bcl-2 in MACs, and to compare these patterns with two MAC histologic stimulants: sclerosing type basal cell carcinomas (sBCCs) and desmoplastic trichoepitheliomas (dTEs). Other objectives were to compare expression patterns of cytokeratin (CK) AE1/AE3, CK7, CD20, endothelial membrane antigen (EMA), Ber-EP4, CD34, -smooth muscle actin (SMA), and S-100 protein in MACs with its histologic simulators, and to determine the usefulness of all the immunohistochemical studies in diagnosis.

Immunohistochemical markers were performed on 10 MACs, 10 sBCCs, and four dTEs. They included p53, Ki-67, c-erbB-2, Bcl-2, CK AE1/AE3, CK7, CD20, EMA, Ber-EP4, CD34, S-100 protein, and -SMA. MACs expressed p53 in less than 25% of the tumor cells in only two cases (20%), and both cases showed only moderately intense staining, whereas 80% of the sBCCs were positive and showed intense staining, and all dTEs were negative. In MACs, less than 5% of the tumor cells were Ki-67 positive, whereas the sBCCs showed 20% to 40% Ki-67-positive tumor cells and dTEs showed rare Ki-67-positive cells. Bcl-2 was expressed focally in MACs, diffusely in sBCCs, and in scattered cells in dTEs. All tumors were negative for c-erbB-2. CD34, CK7, EMA, Ber-EP4, S-100 protein, and -SMA all showed a distinctive pattern of staining in MACs.

Although MACs arise commonly in chronically sun-exposed skin, increased expression of p53 is not found frequently. Overexpression of c-erbB-2 does not appear to be a factor in the development and progression of these adnexal tumors. Bcl-2 is expressed in MACs, but not diffusely as in sBCCs. The low level of Ki-67 supports a low proliferative rate, and other immunohistochemical markers support divergent patterns of adnexal differentiation in MACs. Immunohistochemical studies may help to differentiate MAC from sBCCs and dTEs.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
ADENOSQUAMOUS CELL CARCINOMA  

Adenosquamous carcinoma of the skin: a report of 10 cases.

Banks ER, Cooper PH.

Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.

J Cutan Pathol 1991 Aug;18(4):227-34 Abstract quote

Cutaneous squamous carcinoma with true glandular differentiation has only rarely been documented.

Ten patients with such tumors are presented. There were six men and four women, aged 48 to 87 years. The tumors were located on the central face (eight), scalp (one), and hand (one) and consisted of minimally elevated, indurated, keratotic plaques, up to 6 cm in size.

Microscopically, the neoplasms exhibited multifocal origin from the epidermis; deep, dispersed, infiltrative growth; perineural invasion; and stromal desmoplasia. Squamous differentiation was most marked superficially. Glandular differentiation was more obvious in deeper areas. Lumens typically developed within squamous nests and were often lined by cells with cytoplasmic vacuoles, some of which contained mucin. The neoplastic cells had obvious cytologic atypia and easily identified mitotic figures. Immunohistochemically, nine neoplasms studied contained carcinoembryonic antigen in glandular foci.

Each patient had one or more surgical resections, and six also received radiation and/or chemotherapy. Five patients died with uncontrolled local recurrence, and two are alive with extensive disease and clinical evidence of regional lymph node involvement. Two individuals with small, superficial neoplasms that could be completely removed are disease free. One patient died of unrelated causes shortly after diagnosis.

Cutaneous adenosquamous carcinoma is more aggressive than the usual carcinoma of the skin. It must be distinguished from the cytologically bland, microcystic adnexal (sclerosing sweat duct) carcinoma which is capable of recurring but rarely, if ever, proves fatal. The question of whether adenosquamous carcinoma is an epidermally derived squamous tumor with divergent differentiation or should be viewed as a newly recognized adnexal carcinoma remains to be resolved.

Syringoma  
Sclerosing basal cell carcinoma  
Desmoplastic trichoepithelioma  
Monoclonal antibody Ber-EP4 reliably discriminates between microcystic adnexal carcinoma and basal cell carcinoma.

Institut für Dermatohistologie, Heidelberg, Germany.

 

J Cutan Pathol. 2007 Oct;34(10):782-7. Abstract quote

Background: Sclerosing cutaneous neoplasms often represent a diagnostic challenge. The monoclonal antibody Ber-EP4 recognizes two glycopolypeptides found in most human epithelial cells. It is diagnostically highly reliable in the differentiation between basal cell carcinoma and cutaneous squamous cell carcinoma. In this study, we report its application in the differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and basal cell carcinoma.

Methods: Biopsy samples from 28 sclerosing and infiltrating basal cell carcinomas, 13 microcystic adnexal carcinomas and 16 desmoplastic trichoepitheliomas were examined after immunohistochemical staining with Ber-EP4.

Results: Ber-EP4 did not label any of the microcystic adnexal carcinomas, whereas all 28 basal cell carcinomas were Ber-EP4 positive. Twenty-seven of the 28 showed moderate or strong staining intensity, with the majority being strong. Only one basal cell carcinoma was weakly positive. Twelve of the 16 desmoplastic trichoepitheliomas were immunoreactive with Ber-EP4 and the staining was more variable than those of basal cell carcinomas.

Conclusions: Ber-EP4 reliably differentiates microcystic adnexal carcinoma from basal cell carcinoma to the same extent as it distinguishes the latter tumor from squamous cell carcinoma. While it stains the majority of desmoplastic trichoepitheliomas, these tumors still have to be considered in the differential diagnosis with microcystic adnexal carcinoma, when Ber-EP4 is applied.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
Prognostic Factors Complete excision is the most important factor in ensuring cure

Microcystic adnexal carcinoma: report of 13 cases and review of the literature.

Snow S, Madjar DD, Hardy S, Bentz M, Lucarelli MJ, Bechard R, Aughenbaugh W, McFadden T, Sharata H, Dudley C, Landeck A.

Department of Surgery, University of Wisconsin-Madison, School of Medicine, 2880 University Ave., Madison, WI 53705, USA.

Dermatol Surg 2001 Apr;27(4):401-8 Abstract quote

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare tumor of the skin. Clinically it often masquerades as a firm, subcutaneous nodule on the head and neck regions. Microscopically it extends far beyond assessed clinical margins spreading locally in the dermal, subcutaneous, and perineural tissue planes. The local recurrence rate by standard excision is about 50%. Recent preliminary reports indicate more favorable cure rates with Mohs micrographic surgery (MMS).

OBJECTIVE: To present our data on 13 cases (12 patients) of MAC treated by MMS. In addition, we reviewed the medical literature to summarize the accumulated experience of MMS treatment in the management of MAC. We also present a case of bilateral MAC of the face and describe a renal transplant recipient on immunosuppressive therapy who developed MAC of the nasal bridge.

METHODS: We reviewed and updated our series of MAC cases treated by MMS over the last 9 years. A total of 13 cases of MAC are reviewed. We also searched the literature for MAC treated by MMS with a follow-up of more than 2-years.

RESULTS: One patient had bilateral MAC of the nose and cheek. Another patient developed a MAC of the nasal bridge 20 years after renal transplantation. In this patient predisposing factors were radiation for teenage acne and immunosuppression therapy. A total of 13 cases of MAC were treated by MMS with no recurrences, with a mean follow-up of 5.0 years (range 1.1-8.0 years).

CONCLUSION: We update the medical literature with 13 MAC cases treated by MMS. To our knowledge there have been 148 cases of MAC reported in the world literature. Including our series, there have been 73 cases of MAC treated with MMS. There were only four treatment failures. Regional and/or distant metastasis from MAC is rare, with only one reported death. Following MMS, the 2-year success rate was 89.7% (35 of 39). The accumulated data continue to confirm that when MAC is discovered early and is readily accessible to excision by MMS and other subspecialty support, a favorable outcome can be expected.

Recurrence J Am Acad Dermatol 1999;41:225-231
If complete excision is not achieved, as much as 30-50% of cases may have local recurrence
Metastasis

Laryngoscope 1995;105:1197-1201
Regional lymph nodes

Some have suggested that this was direct extension rather than lymphatic spread

Microcystic Adnexal Carcinoma with Mandibular Bone Marrow Involvement: A Case Report with Immunohistochemistry.

From the Departments of *Oral Pathology and Medicine; section signOral and Maxillofacial Reconstructive Surgery; ||Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; daggerUniversity of the East, College of Dentistry, Manila, Philippines; and double daggerDepartment of Oral Pathology, Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya, Malaysia.

Am J Dermatopathol. 2006 Dec;28(6):518-522. Abstract quote

Microcystic adnexal carcinoma is a rare, locally aggressive cutaneous neoplasm with a high probability of persistence locally but a low probability of metastasis.

We report a case of a 69-year-old female patient with an indurated plaque at the mental region. Histologically, the tumor cells invaded the subcutaneous tissue and mandibular bone. The tumor consisted mainly of squamous and basaloid epithelial nests and cords embedded in a desmoplastic stroma. A few keratin-filled microcysts and ductal structures were also observed. Perineural encroachment was also noted but there was no mitosis, cytologic features of malignancy, or metastasis. The epithelial nests were positive to various cytokeratins except for CK20 and the lumina of the ductal structures were positive to carcinoembryonic antigen.

Our results indicate that microcystic adnexal carcinoma consists of tumor cells capable of both follicular and eccrine differentiation. It is locally aggressive, extends far beyond its clinical presentation and may involve the bone. It may persist and remain asymptomatic for so many years without metastasis. A lifetime postsurgery monitoring is mandatory to ensure early and proper management.

Metastatic microcystic adnexal carcinoma in an immunocompromised patient.

Carroll P, Goldstein GD, Brown CW Jr.

Department of Internal Medicine, University of Kansas Medical Center, Lawrence, Kansas, USA

Dermatol Surg 2000 Jun;26(6):531-4 Abstract quote

BACKGROUND: Microcystic adnexal carcinoma is an uncommon, locally aggressive cutaneous neoplasm. To date, there are only two reports of histologically proven lymph node involvement with this tumor. We describe a case of a patient with microcystic adnexal carcinoma who developed multiple local metastasis in transit with histologically proven lymph node involvement and was diagnosed with chronic lymphocytic leukemia.

OBJECTIVE: To describe the details of our case and to review what is currently known about this tumor.

METHODS: Mohs micrographic surgery was utilized for tumor removal.

RESULTS: This patient developed multiple tumors of the scalp over the period of a 1 year which were histologically proven to be microcystic adnexal carcinoma. All tumors were noncontiguous and presented on the scalp. During the histologic analysis of the last tumor removed by Mohs micrographic surgery a lymph node was resected which revealed infiltrative microcystic adnexal carcinoma.

CONCLUSIONS: We present the case of an immunocompromised patient treated for microcystic adnexal carcinoma with Mohs micrographic surgery who proceeded to develop local metastasis in transit.

TREATMENT

J Dermatol Surg Oncol 1994;20:429-434
J Am Acad Dermatol 1999;41:225-231
Wide local excision
MOHS micrographic surgery may be used to provide complete removal

One study found 0/22 (0%) of cases recurred if MOHS was performed

SURGERY  
Microcystic adnexal carcinoma: treatment with Mohs micrographic surgery.

Leibovitch I, Huilgol SC, Selva D, Lun K, Richards S, Paver R.

Department of Ophthalmology, Oculoplastic and Orbital Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

J Am Acad Dermatol. 2005 Feb;52(2):295-300. Abstract quote

BACKGROUND: Microcystic adnexal carcinoma (MAC) is reported to have a high rate of recurrence with standard wide local excision.

OBJECTIVE: To report a large series of patients with MAC treated with Mohs micrographic surgery (MMS).

METHODS: This prospective, multi-center case series included all patients in Australia treated with MMS for MAC, who were monitored by the Skin and Cancer Foundation between 1993 and 2002.

RESULTS: There were 44 cases; most of them (90.9%) were located in the head and neck area. In 31.8% of cases it was a recurrent tumor. In 32.5% of cases the tumor was initially misdiagnosed as basal cell carcinoma or squamous cell carcinoma. Perineural invasion was recorded in 17.5% of cases; most of them (85.7%) were previously recurrent tumors. There was only one case of recurrence (5%) out of 20 patients who completed a 5 year follow-up period after MMS.

CONCLUSION: The low 5-year recurrence rate of MAC with MMS emphasizes the importance of margin-controlled excision.

Microcystic adnexal carcinoma. Ten cases treated by Mohs micrographic surgery.

Burns MK, Chen SP, Goldberg LH.

Baylor College of Medicine, Houston, Texas.

J Dermatol Surg Oncol 1994 Jul;20(7):429-34 Abstract quote

BACKGROUND. Microcystic adnexal carcinoma is a slow-growing, nondescript, locally aggressive, deeply infiltrating neoplasm histologically characterized by an infiltrative pattern of basaloid or squamous cells, a desmoplastic stromal reaction, keratin-filled cysts, and glandular structures.

OBJECTIVE. Microcystic adnexal carcinoma is uncommon and may be mistaken microscopically for other benign and malignant entities. Perineural or intraneural involvement by tumor cells is characteristic and extension into underlying structures including muscle, fat, and bone are frequently encountered. Although local recurrences are common after standard surgical excision, metastases have not been reported. Extensive resections of lesions may be necessary to extirpate widespread tumor, particularly those that are long standing or recurrent. Because significantly increased morbidity is associated with recurrent disease, surgical and histopathologic techniques that stress examination of all margins are advantageous.

METHODS. We review the course of 10 patients with microcystic adnexal carcinoma of the face (six primary and four recurrent lesions) and their treatment by Mohs micrographic surgery.

Microcystic adnexal carcinoma: collaborative series review and update.

Friedman PM, Friedman RH, Jiang SB, Nouri K, Amonette R, Robins P.

Department of Dermatology, New York University School of Medicine, New York, 10016, USa.

J Am Acad Dermatol 1999 Aug;41(2 Pt 1):225-31 Abstract quote

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a malignant appendageal tumor first described in 1982. It can be clinically and histologically confused with other malignant and benign cutaneous neoplasms, leading to inadequate initial treatment. This neoplasm is locally aggressive and deeply infiltrating, characterized by high morbidity and frequent recurrence. Mohs micrographic surgery has been used to conserve tissue and improve the likelihood for cure.

OBJECTIVE: We report our experience using Mohs micrographic surgery for the treatment of MAC and compare with earlier reports in the literature. In addition, we review the epidemiology, clinical and histologic characteristics, and optimal treatment of this rare neoplasm. We also describe a 15-year-old white male patient with MAC on the scalp occurring only 7 years after radiation exposure.

METHODS: The medical records of 11 patients with MAC who were treated by Mohs micrographic surgery were reviewed at both departments, and follow-up data were obtained.

RESULTS: In all patients treated with Mohs micrographic surgery, there were no recurrences after a mean follow-up of 5 years.

CONCLUSION: Mohs technique enables the detection of clinically unrecognizable tumor spread and perineural invasion often encountered with MAC. Aggressive initial treatment by microscopically controlled excision appears to offer the greatest likelihood of cure for this neoplasm, while providing conservation of normal tissue. In addition, we describe the second youngest patient with MAC and readdress the issue of previous radiotherapy as an important predisposing factor.

Microcystic adnexal carcinoma: forty-eight cases, their treatment, and their outcome.

Chiller K, Passaro D, Scheuller M, Singer M, McCalmont T, Grekin RC.

Department of Dermatologic Surgery, University of California, San Francisco, 1701 Divisadero St, Third Floor, San Francisco, CA 94143, USA.

Arch Dermatol 2000 Nov;136(11):1355-9 Abstract quote

BACKGROUND: Microcystic adnexal carcinoma, or sclerosing sweat duct carcinoma, is an uncommon cutaneous neoplasm associated with extensive local invasion. The standard of care with regard to the best excisional method in treating microcystic adnexal carcinoma has not been established.

OBJECTIVES: To perform a retrospective study comparing patients treated by Mohs micrographic surgery with those treated by wide excision and to elucidate the epidemiological features of microcystic adnexal carcinoma.

PATIENTS AND METHODS: A retrospective analysis of a case series involving 48 primary and referral patients diagnosed as having microcystic adnexal carcinoma using standardized criteria. All cases were reviewed by the same dermatopathologists.

RESULTS: Microcystic adnexal carcinoma predominantly affects the left side of the face of middle-aged women. Microcystic adnexal carcinoma is misdiagnosed 30% of the time. The recurrence rate is 1.98% per patient-year. Mohs micrographic surgery and simple excision show comparable complication rates. Clear margins were obtained in fewer procedures and, therefore, fewer office visits when the lesions were treated with micrographic surgery. The defect surface area after full extirpation following Mohs micrographic surgery was a mean of 4 times that of the clinically apparent size. The wide range of difference between the pre- and the post-Mohs micrographic surgery surface area noted in our data indicates that a margin cannot be safely predicted.

CONCLUSIONS: Microcystic adnexal carcinoma is a predominantly left-sided, locally aggressive facial tumor, which results in significant morbidity. Our data do not support the use of standardized predictable margins. Mohs micrographic surgery is a reasonable initial treatment, as it accomplishes cure in fewer office visits and does not rely on predicted margins.

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008


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