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Background

This is a broad category of tumors arising from the apocrine glands of the skin. Many of the tumors show considerable histologic similarity to tumors arising within the salivary glands and breast.

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HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  
ADENOSIS TUMOR OF ANOGENITAL MAMMARY-LIKE GLANDS  
Adenosis tumor of anogenital mammary-like glands: a case report and demonstration of clonality by HUMARA assay.

Kazakov DV, Bisceglia M, Sima R, Michal M.

Sikl's Department of Pathology, Charles University, Medical Faculty Hospital, Pilsen, Czech Republic.

J Cutan Pathol. 2006 Jan;33(1):43-6. Abstract quote  

In mammary pathology, adenosis tumor is defined as a clinically recognizable lesion that histologically primarily consists of adenosis, but also exhibits various combinations of diverse epithelial changes seen in other benign breast diseases.

A lesion that occurred in the anogenital area of a 46-year-old woman and apparently arose in anogenital mammary-like glands is described and which, in our opinion, is best classified as adenosis tumor. A biopsy revealed a well-demarcated, unencapsulated lesion surrounded by compressed fibrous tissue forming a pseudocapsule. Several histological patterns within the same tumor mass were recognizable: sclerosing adenosis-like changes, variably sized microcysts and cysts, some with rare short papillary projections having hyalinized cores, rare tubular structures exhibiting epithelial features reminiscent of simple ductal hyperplasia, areas with oxyphilic (apocrine) metaplasia, and clear cell epithelial changes resembling mucinous metaplasia. Decapitation secretion was notable in many lumens. Rare lumens were filled with foamy macrophages. There were also focal clear cell changes of myoepithelial cells. The stroma was paucicellular and sclerotic in some foci and composed of myofibroblasts and myxoid in others.

Calponin, actins, and p63 stained myoepithelial cells. The cells in the oxyphilic (apocrine) metaplasia areas stained for mitochondrial antigen and Bcl-2. Antibodies to progesterone and estrogen receptor stained approximately 50 and 20% of the epithelial cell population, respectively. Human androgen receptor gene analysis yielded a monoclonal pattern. As our case exhibited a number of patterns identical to those seen in diverse benign breast diseases, its classification as adenosis tumor seems justifiable.

This cutaneous perianal lesion is indistinguishable microscopically from its mammary analogue and was clinically detectable.
FOX-FORDYCE DISEASE  
Dilation of apocrine glands. A forgotten but helpful histopathological clue to the diagnosis of axillary Fox-Fordyce disease.

Department of CIPAX-Medicina Diagnostica, Sao Jose dos Campos-SP, Brazil.

Am J Dermatopathol. 2009 Jun;31(4):393-7. Abstract quote

Fox-Fordyce disease is a condition with protean histopathological alterations whose pathogenesis remains a mystery. Although recent studies have addressed histological changes specific of this disease, including perifollicular xanthomatosis, no attention has been given to apocrine acini dilation as an adjunct histopathological finding to the diagnosis. Moreover, although previous efforts were done to demonstrate that perifollicular foamy histiocytes harbor apocrine secretion content, this concept has not been proved to date.

In this study, we report 2 cases harboring prominent dilation of apocrine coils with mucinous content. Such mucinous content showed mucin profile identical to the dermal mucin deposits in both cases. Of note, perifollicular foamy histiocytes demonstrated cytoplasmic mucin, supporting the suggestion that these cells phagocytose apocrine secretion. Although not specific, apocrine coil dilation is another histopathological feature of Fox-Fordyce disease and it may be used as a low-power magnification clue for the correct diagnosis.

We also propose that the so-called perifollicular xanthomatosis may be composed of muciphages or mixed cell (muciphages/xanthomatous) population, an issue that should be further investigated in future studies.
HIDRADENOMA PAPILLIFERUM  
Hidradenoma papilliferum with oxyphilic metaplasia: a clinicopathological study of 18 cases, including detection of human papillomavirus.

Kazakov DV, Mikyskova I, Kutzner H, Simpson RH, Hes O, Mukensnabl P, Bouda J, Zamecnik M, Kinkor Z, Michal M.

Sikl's Department of Pathology, Charles University, Medical Faculty Hospital, Pilsen, Czech Republic.

Am J Dermatopathol. 2005 Apr;27(2):102-10. Abstract quote  

Reported here are 18 cases of hidradenoma papilliferum with oxyphilic metaplasia. All patients were women ranging in age from 29 to 74 years. Each presented clinically with a small, solitary tumor in the anogenital region.

Microscopically, in addition to classic histopathological features, in every case there was oxyphilic metaplasia of the constituent epithelial cells. This finding could be likened to apocrine metaplasia, a term used in breast pathology. Other histopathological findings observed in this series, analogous to benign breast disease, included sclerosing adenosis-like changes, atypical apocrine adenosis-like changes, changes corresponding to usual ductal epithelial hyperplasia, epitheliomatosis with a streaming growth pattern, lamprocyte-like changes, clear cell change of the myoepithelium, foamy histiocyte reaction, and stromal fibrosis. Immunohistochemistry inferred that in the majority of cases oxyphilic metaplasia resulted from more lysosomes, whereas numerous mitochondria were detected in only 3 cases. Using 2 different PCR methods we identified HPV in 4 of 15 cases of hidradenoma with oxyphilic metaplasia. In addition, HPV was detected in 3 of 16 conventional papillary hidradenomas used as a control group. The following HPV types were identified: 16, 31, 33, 53, and 56. The last type was found in 5 cases. More than one HPV type from a single lesion was seen in 5 cases.

Our observations are consistent with previous publications noting similarities between tumors of the breast and sweat glands. Oxyphilic metaplasia, areas with solid growth, and changes simulating atypical apocrine adenosis are rare and poorly recognized in hidradenoma papilliferum and may cause diagnostic difficulties; in our cases several submitting pathologists suspected malignancy.

A causal role for HPV in hidradenoma papilliferum cannot be confirmed from our results, as the detection rate is too low. The exact role of the HPV in etiology and pathogenesis of this neoplasm has yet to be determined.
SYRINGOCYST-ADENOMA PAPILLIFERUM  

Syringocystadenoma papilliferum contiguous to a verrucous cyst.

Li A, Sanusi ID, Pena JR, Nopajaroonsri C, Kent M, Smoller BR.

Department of Pathology, Louisiana State University Health Sciences Center in Shreveport; Dermatology Clinic and Department of Pathology, VA Medical Center in Shreveport; and Departments of Pathology and Dermatology, University of Arkansas for Medical Sciences, AR, USA.

J Cutan Pathol 2003 Jan;30(1):32-36 Abstract quote

BACKGROUND: Syringocystadenoma papilliferum (SCAP) and verrucous cyst are two uncommon benign tumors. The simultaneous occurrence of the two lesions has not been reported before.

METHODS: We report four cases of the simultaneous occurrence of the two rare lesions as so-called collision lesions with a review of the literature.

CONCLUSION: The relationship of SCAP with viral infection needs further investigation.

TUBULAR ADENOMA  
Tubular Adenoma of the Skin with Follicular and Sebaceous Differentiation: A Report of Two Cases.

Kazakov DV, Mukensnabl P, Michal M.

Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Pilsen, Czech Republic
Am J Dermatopathol. 2006 Apr;28(2):142-146. Abstract quote  

The main controversies regarding tubular apocrine adenoma and papillary eccrine adenoma are whether they are two distinct entities or are the very same tumor, and if so, which lineage of differentiation (apocrine versus eccrine) it pursues.

We report two cases of tubular adenoma with follicular and, in one case, additionally, sebaceous differentiation. The features in both cases indicated apocrine differentiation of the tubular component. One patient was a 60-year-old woman with a 1-year history of a solitary nodule on the scalp. The other patient was a 48-year-old woman with a solitary nodule of unknown duration located on the back. In both patients, the tumors were surgically removed. The patients were alive and well 2.5 and 2 years after surgery, respectively.

The histologic features that both cases had in common included the combination of a tubular adenoma, foci of follicular differentiation, and areas of immature squamous metaplasia. In case 1, follicular differentiation was seen in the form of strands of basaloid cells surrounded by a stroma resembling the embryonic perifollicular sheath. Some aggregates of basaloid cells were juxtaposed with small collections of plump fibroblasts, imparting a resemblance to rudimentary follicular germs associated with follicular papillae. Many minute lumens surrounded by more eosinophilic cells were seen within the strands. In case 2, follicular differentiation was seen as several infundibulocystic structures surrounded by isthmic epithelium housing scattered mature sebocytes. In addition, there were areas reminiscent of desmoplastic trichoepithelioma (columnar trichoblastoma). In both cases, the areas with immature squamous metaplasia were represented by solid nodules that were mostly devoid of lumens and a peripheral basal/myoepithelial cell layer.

In conclusion, these two cases of cutaneous tubular adenoma with accompanying follicular and sebaceous differentiation give further support to the proposition that the majority of these neoplasms have apocrine differentiation. Rare cases occurring in the sites normally devoid of apocrine glands may represent the eccrine counterpart.
APOCRINE CARCINOMA  

Her-2 expression in cutaneous eccrine and apocrine neoplasms.

Hiatt KM, Pillow JL, Smoller BR.

1Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Mod Pathol. 2004 Jan;17(1):28-32. Abstract quote  

Cutaneous eccrine and apocrine glands have many histologic and immunologic similarities to ducts and acini of the breast.

Thus, differentiating a primary cutaneous process from a metastatic breast carcinoma can be nearly impossible. In all, 10-34% of breast carcinomas overexpress HER-2 protein, a membrane-associated protein that functions in cell differentiation, adhesion and motility.

As expression of this gene in cutaneous neoplasms has not been well characterized, we sought to determine HER-2 expression in a sample of benign and malignant cutaneous eccrine and apocrine neoplasms and to determine if there is value in using this protein expression in differentiating primary cutaneous from metastatic breast lesions. Totally, 85 primary cutaneous neoplasms and 11 cutaneous metastases from HER-2-positive breast carcinomas were retrieved from archived material at our institute.

All cases were evaluated for HER-2 protein expression using the Dako Hercept Test kit. Membranous HER-2 staining was noted in three of the 85 cutaneous adnexal neoplasms: one hidrocystoma and two nodular hidradenomas. Seven of the 11 cutaneous metastases from HER-2-positive breast carcinomas maintained moderate-to-strong HER-2 expression.

In conclusion, while 10-34% of breast carcinomas overexpress the HER-2 protein, only 3.5% of cutaneous apocrine and eccrine neoplasms in this study stained with the HER-2 antibody. These HER-2-positive cutaneous neoplasms typically do not pose a diagnostic dilemma in the setting of differentiation from breast metastasis. Additionally, although histologically these breast and cutaneous lesions may have morphologic similarities, the relative lack of HER-2 overexpression suggests that they are different nosologically. Finally, this study suggests that HER-2 protein expression can be a useful tool in differentiating a primary cutaneous appendageal neoplasm from HER-2 expressing metastatic breast carcinoma.

Apocrine carcinoma of the skin. A clinicopathologic, immunocytochemical, and ultrastructural study.

Paties C, Taccagni GL, Papotti M, Valente G, Zangrandi A, Aloi F.

Department of Pathology, Piacenza Civil Hospital, Italy.

Cancer 1993 Jan 15;71(2):375-81 Abstract quote

BACKGROUND. Apocrine carcinomas of the skin are rare and incompletely studied neoplasms.

METHODS. An immunohistochemical and ultrastructural study is reported of specimens from six patients with apocrine skin carcinoma in various body sites. Three tumors were in the axilla; one, the eyelid; one, the ear; and one, the scalp. There were three local recurrences and three regional lymph node metastases, but no patient died of cancer (follow-up, 2-10 years).

RESULTS. The most reliable histopathologic criteria for identifying apocrine skin carcinoma appear to be decapitation secretion, periodic acid-Schiff-positive diastase-resistant material in the cells or lumen, and immunoreactivity with gross cystic disease fluid protein 15. All specimens expressed common epithelial antigens (cytokeratins, carcinoembryonic antigen, and epithelial membrane antigen) and histiocytic-secretive antigens (Leu-M1, lysozyme, LN5, alpha-1-antitrypsin, and alpha-1-antichymotrypsin). S-100 protein was found in the three nonaxillary tumors. Ultrastructurally, the primary tumors, and especially the secondary lesions, were dedifferentiated compared with normal apocrine glands.

CONCLUSIONS. Apocrine differentiation in skin tumors does not indicate an exclusive origin from the apocrine sweat glands; these neoplasms usually have an indolent clinical course.

CRIBRIFORM CARCINOMA  
Primary cutaneous cribriform carcinoma: a rare apocrine tumour.

Adamski H, Le Lan J, Chevrier S, Cribier B, Watier E, Chevrant-Breton J.

Department of Dermatology, University of Rennes, Rennes, France.


J Cutan Pathol. 2005 Sep;32(8):577-80. Abstract quote  

Background: Primary cutaneous cribriform carcinoma (PCCC) is a rare apocrine tumour occurring in middle-aged people. This neoplasm is often located on the limbs. The histopathological diagnosis is difficult, mainly because this tumour is exceptional. We, in this study, report a patient with PCCC.

Case report: The patient was a 37-year-old man who presented with a nodule of the left knee. Results: Histopathologic findings showed an asymmetrical deep dermal tumour with a cribriform pattern. The aggregations of neoplastic cells were interconnected and varied in size and shape. The cells were arranged in solid nests or tubular structures. In the lumina of tubules, some papillary protrusion of basophilic cells was seen. The ductal elements were lined by cuboidal or cylindric cells with images of decapitation secretion. The nuclei of the neoplastic cells were pleomorphic. A wide excision was performed with sentinel inguinal node biopsy. After a 2-year follow-up, neither persistence at the local site nor metastasis was observed.

Conclusions: Clinical and pathological features of PCCC are reviewed. Differential diagnoses, including cutaneous metastasis of adenocarcinoma, adenoid basal cell carcinoma and adenoid cystic carcinoma, are discussed.

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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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Last Updated June 15, 2009

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