Apocrine and eccrine adnexal tumors
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1 Apocrine and eccrine adnexal tumors Timothy McCalmont, MD University of California San Francisco, CA
2 Past misguided notions Syringoma is eccrine Eccrine poroma rather than eccrine or apocrine poroma Spiradenoma is eccrine while its sibling cylindroma is apocrine Microcystic adnexal carcinoma shows mixed follicular and eccrine differentiation
3 Timothy H. McCalmont, M.D.
4 Factors crucial to the evaluation of adnexal lineage Embryology Combined and associated tumors Anatomic distribution Morphology & phenotype By light microscopy, EM, and immunostaining
5 Embryology. Apocrine differs from eccrine
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7 Folliculosebaceousapocrine unit
8 Does ontogeny reflect phylogeny? Alleged combinations of eccrine and follicular (or eccrine and sebaceous) are probably fictional
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23 Syringocystadenoma papilliferum
24 Nevus sebaceus and secondary neoplasms Syringocystadenoma (apocrine) Trichoblastoma (follicular) Trichilemmoma (follicular) Sebaceous adenoma (sebaceous) Tubular adenoma (apocrine) Poroma (apocrine, when occurring in nevus sebaceus)
25 Combined tumors.
26 Combined tumors Elements that commonly occur conjointly, non-coincidentally, are of related lineage Example: glomangiomyoma
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29 Combined adnexal tumors Spiradenoma and cylindroma Spiradenoma and trichoepithelioma Cylindroma and trichoepithelioma Tubular adenoma and sebaceous adenoma
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33 Spiradenoma
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36 Cylindroma
37 Q.E.D. Trichoepithelioma, spiradenoma, and cylindroma are all folliculosebaceous-apocrine
38 Neoplastic associations (syndromic)
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43 What s the lesson of Brooke-Spiegler? The combination of spiradenoma with cylindroma and trichoepithelioma in a genetic syndrome indicates folliculosebaceous-apocrine lineage
44 Anatomic distribution.
45 Distribution of adnexa The distribution of adnexal tumors parallels the structures toward which they differentiate
46 Trichoblastoma (trichoepithelioma)
47 Trichoblastoma Sex 72:28 (F>M) Age 3-99 years head/neck 96% arm/leg 4% hand/foot <1%
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49 Syringoma Sex 79:21 (F>M) Age yrs head/neck 90% axilla/genital 5% arm/leg 5% hand/foot <1%
50 (Arch Dermatol 113: , 1977)
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52 Spiradenoma Sex 53:47 (F>M) Age years head/neck/trunk 76% arm/leg 24% hand/foot <1%
53 Houston, we have a problem. If spiradenoma or syringoma were purely eccrine, we d see them as palmoplantar tumors
54 Morphology.
55 Morphologic attributes Light microscopic pattern Immunophenotype (immunohistochemistry) Enzyme expression (histochemistry) Ultrastructure (electron microscopy)
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57 Follicular attributes Basaloid (germinative) cells with adjacent mesenchymal cells (resembling the bulb and papilla) Matrical ( shadow ) cells Pallid (outer sheath) cells with adjacent thickened membrane Trichohyaline granules
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59 Sebaceous attributes Cells with coarsely vacuolated cytoplasm and scalloped nuclei
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61 Apocrine attributes Decapitation? Cuticulated ducts? Pallid (clear) cells? Eccrine attributes Cuticulated ducts? Pallid (clear) cells?
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63 Immunohistochemical reagents Carcinoembryonic antigen (CEA) S100 protein Gross cystic disease fluid protein (GCDFP-15) Epithelial membrane antigen (EMA) Anti-keratins
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66 Morphologic conclusions We can precisely define follicular and sebaceous differentiation We cannot precisely identify apocrine and eccrine lineage
67 Morphologic conclusions The distinction and classification of apocrine and eccrine lesion requires integration of a variety of factors, including embryology, distribution, and microscopy
68 Eccrine Neoplasms Less common than apocrine, probably because of the monophasic nature of the eccrine apparatus of little proliferative potential (hyperproliferation precedes mutagenesis in oncogenesis)
69 Eccrine tumors Syringoma, sometimes Poroma, commonly Hidradenoma, sometimes Papillary adenoma, commonly
70 Poroma Of eccrine or apocrine lineage of palm or sole, manifest as a vascular nodule: eccrine poroma within nevus sebaceus or on axillary skin: apocrine poroma
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79 Poroma Patterns Juxtaepidermal (epidermal and dermal poroma) Intraepidermal (hidroacanthoma simplex) Intradermal (dermal duct tumor)
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88 Poroma Hallmarks Small cuboidal ( poroid ) cells Prominent ductular differentiation Highly vascular stroma Necrosis en masse, sometimes
89 Papillary adenoma A proliferative adenoma, with tubules lined by a cellular multilayered epithelium from which papillary projections extend into the luminal space Eccrine or apocrine in lineage
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94 Aggressive (digital) papillary adenoma
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98 Aggressive papillary adenoma In retrospect, most examples represent malignancy, i.e. papillary adenocarcinoma Of course an adenoma may seem aggressive if it is truly an adenocarcinoma
99 Apocrine tumors Apocrine differentiation often occurs jointly with follicular and sebaceous attributes, thus diverse! Strictly apocrine lesions are often indistinguishable from strictly eccrine neoplasms via conventional microscopy
100 Strictly apocrine tumors Syringoma, commonly Poroma, commonly Hidradenoma, commonly Apocrine adenomas, including hidradenoma papilliferum and syringocystadenoma Spiradenoma and cylindroma
101 Tumors with apocrinefollicular (or folliculosebaceous-apocrine) differentiation Chondroid syringoma (mixed tumor) Microcystic adnexal carcinoma
102 Syringoma Occur at virtually any site; commonly periorbital Uncommon at acral or glabrous sites Apocrine or eccrine in lineage; most are probably apocrine Usually small, often characterized by considerable sclerosis
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110 Syringoma Hallmarks Numerous small nests or ducts, often with a central cuticle Enveloping sclerotic stroma Tadpole or comma-shaped nests, sometimes
111 Hidradenoma Close relative of poroma Usually dermal, usually composed of cells with ample pale eosinophilic cytoplasm ( clear cell hid.) May be cystic ( solid-cystic hid.) Eccrine or apocrine in lineage; most are apocrine
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118 Acrospiroma Bridging designation that encompasses poroma and hidradenoma Equivalent to the garbage can designation nodular hidradenoma
119 Hidradenoma Hallmarks Cuboidal cells, often with pale cytoplasm and generally larger than those of poroma Limited ductular differentiation Solid or cystic or both Stromal sclerosis, often
120 Apocrine adenomas Papillary adenoma Tubular adenoma Tubulopapillary adenoma Hidradenoma papilliferum Syringocystadenoma
121 Hidradenoma papilliferum A papillary adenoma of apocrine lineage with a circumscribed but frond-like pattern Occur on genital skin or in the axillary vault, commonly Unrelated to conventional (simple) hidradenoma
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126 Apocrine adenoma spectrum Tubular adenoma Papillary adenoma Hidradenoma papilliferum Tubulopapillary adenoma Syringocystadenoma papilliferum Periocular apocrine adenoma
127 Spiradenoma A tumor with primitive glandular and little ductular differentiation Simply spiradenoma (not eccrine spiradenoma)
128 Apocrine spiradenoma! Non-volar Coexists with cylindroma Occurs in the breast Coexists with trichepithelioma in Brooke-Spiegler syndrome All suggest folliculosebaceousapocrine lineage
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134 Spiradenoma Has a child s jigsaw puzzle pattern with only a few pieces arrayed in non-complex fashion A trabecular pattern within nodules, with dark peripheral cells and pale central cells Superimposed lymphocytes
135 Cylindroma Also neoplasm of apocrine lineage with primitive glandular differentiation
136 Multinodular cylindroma ( turban tumor ) (Weyers et al)
137 Cylindroma Has an adult jigsaw puzzle pattern with 500 interlocking pieces arrayed in a complex pattern Often deposition of basement membrane material in small droplets within nests or circumferentially around nests
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145 Mixed tumor (chondroid syringoma) A hamartoma-like proliferation with tubular and ductular epithelial structures enveloped by equal proportions of mesenchyme Stroma may be cartilaginous ( chrondroid ), myxoid, fibrocytic, adipocytic, or a mix
146 Mixed tumor Most (90%) display prominent apocrine differentiation May observe follicular germinative, outer sheath, isthmic or infundibular, or sebaceous diff. AKA: pleomorphic adenoma
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153 Am J Dermatopathol 1992; 14:186-94: Apocrine type of cutaneous mixed tumor with follicular & sebaceous differentiation. Requena L et al
154 Mixed tumor Mixed tumors may also show strictly ductular differentiation, uncommonly
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158 Microcystic adnexal carcinoma (MAC) Rare, but among the most common adnexal carcinomas Presents on the head and neck, most commonly Slow growing, with onset often backdated to 20s or 30s
159 MAC Typified by combined follicular and glandular differentiation Cytologically bland but architecturally malignant and infiltrative Prone to misdiagnosis, especially in superficial biopsies
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175 MAC Hallmarks Poor circumscription with deep infiltration, often of nerve or muscle Stromal desmoplasia Follicular differentiation, commonly microcystic (infundibular) Ductular differentiation, commonly syringomatous (Remember that syringomatous carcinoma is half a MAC)
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