Extraocular sebaceous carcinoma accompanied by invasive squamous cell carcinoma: The first case report and consideration of histogenesis

A 61‐year‐old man presented with a dome‐shaped nodule, 1.2 cm in size, with a central crater covered by keratinous material near the left lateral malleolus. Histological findings demonstrated a basophilic circular cone in the center, surrounded and sharply demarcated by a broad eosinophilic area. The central conical mass was composed mainly of atypical basaloid cells intermingled with scattered atypical sebaceous cells with scalloped nuclei and microvesicular cytoplasms, suggesting sebaceous carcinoma. The peripheral area consisted of atypical keratinizing squamoid cells without sebaceous cells, suggesting invasive squamous cell carcinoma. Atypical sebaceous cells were positive for adipophilin. Atypical basaloid cells were positive for 34βE12 and CAM5.2. Peripheral squamoid cells were positive for 34βB4 and 34βE12 throughout, and were positive for LHP1 in the superficial layer. We herein describe the first case of extraocular sebaceous carcinoma accompanied by invasive squamous cell carcinoma, which might have arisen from biphasic differentiation of cancer stem cells.     

Intra-epidermal and intra-dermal sebocrine adenoma with cystic degeneration and hemorrhage

BACKGROUND: The ducts of eccrine glands may give rise to intra-epidermal, confluent epithelial and intra-dermal adenomas known as hidroacanthoma simplex, eccrine poroma, and dermal duct tumor, respectively. An apocrine and sebaceous counterpart of the eccrine poroma has been described by several authors as adnexal, poroma-like adenoma with apocrine and sebaceous differentiation or sebocrine adenoma. METHODS: Using clinical history and routine histologic techniques, we describe a new lesion with features similar to sebocrine adenoma but representing the intra-epidermal and intra-dermal counterparts with cystic degeneration and hemorrhage. Briefly, an 84-year-old female presented with a 6 mm dark tan papule on the neck that clinically appeared as an unusual macular seborrheic keratosis with underlying hemorrhage. RESULTS: Histopathological examination showed a benign dermal cystic appendage tumor with pale polygonal cells, occasional non-keratinizing ducts, sebaceous differentiation and central hemorrhage with fibrin deposits. Serial sections did not reveal any epidermal connection. However, epithelioid cells with large nuclei in an intra-epidermal pagetoid pattern were focally seen. CONCLUSION: These findings represent a new cystic, hemorrhagic variant of sebocrine adenoma.     

Apocrine type of cutaneous mixed tumor with follicular and sebaceous differentiation.

Eight cases of apocrine (tubular branching lumina) type cutaneous mixed tumors with follicular and sebaceous differentiation are presented. All eight tumors arose on facial skin; six patients were male and two were female. The lesions showed a cystic or nodular clinical appearance and were surgically excised. Histopathological examination confirmed the diagnosis of apocrine type of cutaneous mixed tumor in each case. Follicular differentiation consisted of (a) keratinous cysts with infundibular keratinization (infundibular differentiation); (b) hair bulbs with papillary mesenchyma, matricial differentiation with basophilic, transitional, and shadow cells, trichohyaline granules, vellous hair shafts, and clear cells of the outer root sheath (anagen differentiation); and (c) epithelial columns composed of inner cells with plump oval nuclei and scant cytoplasm, and similar cells at the periphery that were arranged in a palisade, resembling the inferior segment of a normal hair follicle in telogen. Sebaceous differentiation was represented by mature sebaceous cells, either as single cells or as small islands, within epithelial tracts of the tumor. The proportion of the areas showing these different types of differentiation varied among lesions, but some follicular differentiation was always present, whereas three cases lacked sebaceous differentiation. Immunohistochemical analysis in three cases with respect to their eccrine or apocrine differentiation showed contradictory results as in a previously reported series of cutaneous mixed tumors. The presence of follicular and sebaceous differentiation in the apocrine (tubular branching lumina) type of cutaneous mixed tumor is a confirmation of the apocrine nature of this neoplasm as well as an expression of the common embryologic derivation of all elements of the folliculosebaceous-apocrine unit.     

An Immunohistochemical Study of BCA-225 in Various Skin Cancers

We performed an immunohistochemical study of BCA-225, which is a glycoprotein secreted by the T47D breast carcinoma cell line and recognized by monoclonal antibody BRST-1 (clone name: CU-18), in normal skin and various skin cancers. In normal skin, BCA-225 was positive only in the secretory portion of both eccrine and apocrine glands and in mature cells of the sebaceous gland. We observed 10 cases of squamous cell carcinoma of the skin, 10 cases of basal cell carcinoma without sebaceous differentiation, 3 cases of basal cell carcinoma with sebaceous differentiation, 6 cases of malignant trichilemmoma, 8 cases of eccrine porocarcinoma, 3 cases of ductal carcinoma, 1 case of malignant clear cell hidradenoma, 1 case of apocrine adenocarcinoma, 6 cases of extra-ocular sebaceous carcinoma, 5 cases of extramammary Paget's disease with underlying adenocarcinoma, and 11 cases of extramammary Paget's disease without underlying adenocarcinoma. Most of the cases of sweat gland carcinoma, basal cell carcinoma with sebaceous differentiation, sebaceous carcinoma, and extramammary Paget's disease were positive for BCA-225, while none of the cases of squamous cell carcinoma, basal cell carcinoma without sebaceous differentiation, or malignant trichilemoma were positive. Based on these findings, we believe that BCA-225 is useful in distinguishing tumors with sweat gland and sebaceous differentiation and extramammary Paget's disease from tumors without such differentiation.     

Trichoblastoma arising within an apocrine poroma.

A poroma is a benign neoplasm composed of poroid and cuticular cells and is thought to derive from the eccrine duct. Several recent reports have described cases with sebaceous, follicular, and apocrine differentiation, suggesting a possible apocrine origin, however. Trichoblastoma is a rare benign tumor composed of germinative cells related to the folliculosebaceous-apocrine unit. We report a unique case of a trichoblastoma arising within a poroma with apocrine and sebaceous differentiation. To our knowledge, this exceptional association has not been described previously and may support the theory of the apocrine origin of poromas.     

Microcystic adnexal carcinoma--a light and electron microscopic studies

Microcystic adnexal carcinoma (MAC) in a 48-year-old Japanese male was studied. A firm nodule had appeared on the right side of his upper lip at the age of 38 years and then had gradually enlarged. Light microscopic examinations revealed numerous strands and islands of basaloid cells and keratinous cysts with desmoplastic stroma in the dermis and subcutaneous tissue. Some keratinous cysts showed early calcification and some contained pilar structures. Clear cells resembling sebaceous gland cells were observed in the strands of tumor cells connecting the keratinous cysts. In the middle dermis, there were small ductal structures containing amorphous eosinophilic material. Immunoperoxidase staining for carcinoembryonic antigen was focally positive in the lumina of small ducts, on the ductal lining surface of tumor cells, and in the contents of keratinous cysts. Electron microscopic examinations revealed tumor cells resembling non-keratotic keratinocytes, and containing tonofilaments, mitochondria, and vacuoles. In some parts, tumors were differentiated to various types of sebaceous gland, sweat duct, or sweat secretary segments. Sebaceous gland cells contained lipid droplets and glycogen. Tumors differentiated to sweat duct had a marked similarity to embryo eccrine duct in the lower epidermis because of the presence of multivesicular dense bodies and periluminal filamentous zones and the absence of myoepithelial cells. Tumors differentiated to sweat secretary segments had a similarity to embryo eccrine secretary segments because of the absence of multivesicular dense bodies, periluminal filamentous zones and myoepithelial cells.     

The expression of CD23 in cutaneous non-lymphoid neoplasms

BACKGROUND: Cluster designation 23 (CD23) is generally used as a lymphoid marker. Its utility in cutaneous epithelial tumors has never been studied. In our routine practice, we observed that CD23 reacted strongly with eccrine and apocrine secretory coils. METHODS: Immunohistochemical staining of CD23 was performed in a total of 131 cases of apocrine, eccrine, follicular and other cutaneous non-lymphoid tumors. RESULTS: CD23 expression was detected in all benign apocrine tumors and in half of benign eccrine tumors, particularly those derived from secretory coils. CD23 staining was seen in 42% (8/19) of microcystic adnexal carcinoma (MAC), while no staining was observed in tumor cells of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma and syringoma. All mammary and extramammary Paget's disease were labeled with CD23. In comparison, pagetoid Bowen's disease, melanoma in situ and sebaceous carcinoma exhibited negative staining. In addition, CD23 reacted diffusely with cutaneous mucinous eccrine carcinoma in a manner similar to breast or colonic adenocarcinoma. CONCLUSION: CD23 appears to be a reliable immunohistochemical marker of the eccrine/apocrine secretory coil and helpful in identifying sweat gland tumors of such origin. It is of ancillary value in differentiating MAC from its mimicker. CD23 is a useful addition to the diagnostic immunohistochemical panels for Paget's disease.     

Tubular adenoma of the skin with follicular and sebaceous differentiation: A report of two cases

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.     

Tumor of the follicular infundibulum with sebaceous differentiation

BACKGROUND: Tumor of the follicular infundibulum (TFI) is a relatively rare tumor which clinically presents as a solitary keratotic papule usually on the head and neck which on microscopic examination typically reveals a plate-like fenestrated epithelial tumor composed of pale staining cells. METHODS: We describe a new variant of TFI. An 80-year-old male with a history of multiple basal cell carcinomas and a squamous cell carcinoma presented with a 2-year history of a red, scaly, slightly elevated plaque on the lateral aspect of his right buttock. RESULTS: Histopathological examination revealed plate-like reticulate epithelial outgrowths of large and pale cells with foci of sebaceous differentiation and numerous colloid bodies. Differential diagnosis included superficial basal cell carcinoma with sebaceous and ductal differentiation, tumor of the follicular infundibulum, an unusual fibroepithelioma of Pinkus or an eccrine fibroadenoma with sebaceous differentiation. CONCLUSION: This case illustrates a hybrid adnexal tumor with histologic features common to both tumor of the follicular infundibulum and superficial epithelioma with sebaceous differentiation.     

Ten cases of sebaceous carcinoma arising in nevus sebaceus

Although nevus sebaceus is known to develop various types of secondary neoplasms, it rarely causes carcinoma and only 14 cases of secondary sebaceous carcinoma have been reported. In this study, 10 cases of sebaceous carcinoma arising in nevus sebaceus were collected. The clinicopathological features and results of immunohistochemical examinations with adipophilin, perilipin and p53 were summarized. Sebaceous carcinoma arising in nevus sebaceous predominantly occurred on the scalp (8/10) of elderly women (mean age, 67.7 years). No case was associated with Muir–Torre syndrome. We found several pathological features of sebaceous carcinoma; that is, made up mainly of germinative cells, moderate nuclear atypia without pleomorphism and many mitoses (4–28/10 high‐power field). Adipophilin and perilipin antibodies highlighted lipid drops in the cytoplasm of the malignant cells in all cases. Overexpression of p53 was seen in all cases. In two cases there were coexisting benign‐looking sebaceous lesions at the periphery of the main cancer nodule, and in these lesions p53 showed low positivity compared with the clearly malignant area. There was co‐occurrence of another neoplasm in three cases with trichoblastoma, sebaceoma and syringocystadenoma papilliferum, respectively. All cases were treated by excision of the malignant lesion, with or without inclusion of the nevus sebaceus. In a follow‐up period of 1–7 years, there was no case of recurrence, lymph node metastases or distant metastases. With these specific pathological and immunohistochemical findings using adipophilin, perilipin and p53, we have to consider the possibility that there is a tendency to underdiagnose secondary sebaceous carcinomas in nevus sebaceus. These clinicopathological features of sebaceous carcinomas developing in the nevus sebaceus seem to indicate different biological entities from de novo sebaceous carcinoma.     

Poroma with sebaceous differentiation: Report of three cases

We herein report three cases of poroma, which showed sebaceous differentiation. The patients were two men and one woman, and the involved sites were the thigh, head and back. In all three cases, histopathological examination revealed anastomosing nests consisting of poroid cells proliferating into the dermis. Tubular structures lined by eosinophilic cuticular cells were scattered in the tumour nests. Furthermore, aggregations of mature sebocytes with vacuolated cytoplasm were also observed forming clusters, or intermingled with the poroma cells. Focal calcification was found within the nests in two cases. Sebaceous component were recognized in the presented three cases among the 62 cases (4.8%) examined in our department within the past 10 years. We also include a review of the 31 reported cases of poroma with sebaceous differentiation. None of them occurred in acral regions, where typical eccrine poromas predominate. The majority of cases were benign. This review indicates that some poromas may show sebaceous differentiation and be of apocrine lineage.     

Immunohistochemical study of calretinin in normal skin and cutaneous adnexal proliferations

Calretinin is a calcium-binding protein member of the EF-hand family. The presence of calretinin has been demonstrated in certain stages of the cellular cycle in a wide variety of normal and neoplastic tissues. The main aims of our study were (1) to investigate what structures of the normal skin and cutaneous adnexal proliferations express immunoreactivity for calretinin and (2) to determine the value of immunohistochemical expression for calretinin as a marker for follicular, sebaceous, apocrine, and eccrine differentiation in cutaneous adnexal proliferations. We studied 139 biopsy specimens, including 10 cases of normal skin of different locations and 129 benign and malignant cutaneous adnexal proliferations. In normal skin, we found that calretinin is expressed in the innermost cell layer of the outer root sheath in anagen hair follicle, in both the duct and sebolemma of the sebaceous gland, in the secretory portion of eccrine glands, and in mast cells of the stroma. In cutaneous adnexal proliferations, we found strong immunoreactivity for calretinin in tricholemmal cysts, tricholemmomas/inverted follicular keratoses, tumors of follicular infundibulum, and in some basal cell carcinomas. Focal positivity was also seen in trichoadenomas, trichoblastomas/trichoepitheliomas, pilomatricomas, proliferating tricholemmal tumors, pilar sheath acanthomas, trichofolliculomas, follicular hybrid cysts, cutaneous mixed tumors, steatocystomas, sebaceous hyperplasias, and sebaceomas. These results demonstrate that immunohistochemical study for calretinin may be helpful to identify the innermost cell layer of the outer root sheath in anagen hair follicle and the cutaneous adnexal proliferations showing differentiation toward this structure. Calretinin immunoreactivity supports eccrine differentiation in some sweat gland neoplasms, and it is also useful in identifying neoplasms with ductal sebaceous differentiation.     

Cutaneous spindle cell adenolipoma with eccrine and apocrine differentiation

Cutaneous spindle cell adenolipoma (SCAL) is a recently described rare variant of lipoma with 11 cases reported to date. Here we report a consultation case of a 77-year-old male who presented with a nodule on the right nasolabial fold, diagnosed as apocrine fibroadenoma or sebaceous hyperplasia by an outside pathologist. The specimen revealed an ill-defined dermal tumor composed of mature adipocytes, bland spindle cells, ropey collagen, and dilated eccrine and apocrine glands and ducts in a fibromyxoid stroma. The spindle cells were positive for CD34 and negative for S100 protein and SOX10. These findings are consistent with those of cutaneous SCAL. The pathogenesis of this entity is controversial and includes a hamartomatous process, derivation from adipose tissue surrounding eccrine glands, or preexisting glands entrapment within a growing lipoma. In the present case, the glandular component is extensive and includes both eccrine and apocrine differentiation, which has not been previously described and further supports the hamartomatous nature. Awareness of this rare entity is helpful to prevent confusion with other look-alike primary and metastatic cutaneous lesions.     

Expression of Bcl-x in normal skin and benign cutaneous adnexal tumors

BACKGROUND: Bcl-x appears to have an antiapoptotic role in the epidermis. Little is known about the expression of Bcl-x in cutaneous adnexal structures and benign cutaneous adnexal tumors. METHODS: Tissues from 31 cases of benign cutaneous adnexal tumors (five trichofolliculomas, five trichoepitheliomas, two sebaceous adenomas, five apocrine hidradenomas, five eccrine poromas, five eccrine spiradenomas, and four syringomas) were immunostained for Bcl-x. RESULTS: Strong staining for Bcl-x was seen in cells of the epidermal granular layer and inner root sheath of hair follicles. Sebaceous gland cells showed strong staining. Apocrine gland cells showed weak to moderate staining. No staining was seen in eccrine gland cells. The basaloid cells of trichofolliculomas and trichoepitheliomas showed no staining. In sebaceous adenomas, the sebaceous cells showed strong staining while the basaloid cells were negative. The cells of apocrine hidradenomas showed patchy weak staining. No staining was seen in eccrine poromas, eccrine spiradenomas, and syringomas. CONCLUSIONS: The degree of Bcl-x expression in cutaneous adnexal glandular structures appears to be related to their mode of secretion, being strongest in cells with apoptotic degradation of the entire cell (sebocytes). This pattern is recapitulated in the corresponding benign cutaneous adnexal tumors. Bcl-x may be useful in identifying cells with sebaceous differentiation in poorly differentiated adnexal tumors.     

Sebaceous mantleoma (mantle adenoma): reappraisal of the myth of the problematic benign neoplasm with sebaceous mantle differentiation

Few cases of a true benign neoplasm with sebaceous mantle differentiation have been reported, and little is known about this tumor. Herein, we present a rare case of the neoplasm called sebaceous mantleoma, along with a comparison of the histology and immunoprofile with those of normal sebaceous mantles. A pedunculated polyp occurred on the scalp of a 51‐year‐old woman. Histopathologically, the tumor showed lobulated epithelial‐mesenchymal units that were separated from the normal dermis by clefts. The lesion was composed of cords and columns of basaloid cells containing a few mature sebocytes, with a focal connection to infundibulocystic structures as well as dense fibrotic or fibromyxoid stroma. Immunohistochemically, androgen receptor, estrogen receptor, and CD117 were partially positive for the tumor, and CD8 (C8/144B) and epithelial membrane antigen were focally positive. Additionally, cytokeratin 20‐positive Merkel cells were individually admixed in the tumor nests as well as in normal sebaceous mantles. This case report reveals the characteristic histology and immunoprofile of this problematic benign neoplasm and helps to understand this entity.     

Apocrine poroma with sebaceous differentiation

Poromas have been classified as eccrine neoplasms, but several recent reports of poroid tumors with sebaceous, follicular, and apocrine differentiation have challenged this concept. We report a case of apocrine poroma with sebaceous differentiation. A 69-year-old man presented with an asymptomatic elevated erythematous plaque. Histopathology revealed cellular nests composed of cuboidal poroid cells and sebocytes. The nests varied in size and were entirely intraepidermally arranged in a growth pattern similar to that of hidroacanthoma simplex. Given the common embryologic origin of folliculosebaceous and apocrine units, we believe that this lesion represents an apocrine poroma with sebaceous differentiation.     

Sebocrine adenoma. An adnexal adenoma with sebaceous and apocrine poroma-like differentiation

Sebocrine adenoma is a benign cutaneous adnexal neoplasm differentiating in the direction of sebaceous and apocrine glands. The sebaceous differentiation is characterized by solitary instances or clusters of sebocytes and sebaceous ducts. The apocrine differentiation is characterized by eccrine poroma-like histology. Reported herein are three such cases.     

15-Lipoxygenase-2 expression in benign and neoplastic sebaceous glands and other cutaneous adnexa.

15-Lipoxygenase-2 has a limited tissue distribution in epithelial tissues, with mRNA detected in skin, cornea, lung, and prostate. It was originally cloned from human hair rootlets. In this study the distribution of 15-lipoxygenase-2 was characterized in human skin using immunohistochemistry and in situ hybridization. Strong uniform 15-lipoxygenase-2 in situ hybridization (n = 6) and immunostaining (n = 16) were observed in benign cutaneous sebaceous glands, with expression in differentiated secretory cells. Strong 15-lipoxygenase-2 immunostaining was also observed in secretory cells of apocrine and eccrine glands. Variable reduced immunostaining was observed in skin-derived sebaceous neoplasms (n = 8). In the eyelid, Meibomian glands were uniformly negative for 15-lipoxygenase-2 in all cases examined (n = 9), and sebaceous carcinomas apparently derived from Meibomian glands were also negative (n = 12). The mechanisms responsible for differential expression in cutaneous sebaceous vs eyelid Meibomian glands remain to be established. In epidermis, positive immunostaining was observed in the basal cell layer in normal skin, whereas five examined basal cell carcinomas were negative. Thus, the strongest 15-lipoxygenase-2 expression is in the androgen regulated secretory cells of sebaceous, apocrine, and eccrine glands. This compares with the prostate, in which 15-lipoxygenase-2 is expressed in differentiated prostate secretory cells (and reduced in the majority of prostate adenocarcinomas). The product of 15-lipoxygenase-2, 15-hydroxyeicosatetraenoic acid, may be a ligand for the nuclear receptor peroxisome proliferator activated receptor-gamma, which is expressed in sebocytes, and contribute to secretory differentiation in androgen regulated tissues such as prostate and sebaceous glands.     

Malignant eccrine spiradenoma: a new case report

Malignant eccrine spiradenoma is an extremely rare skin tumor of sweat gland origin. In most cases, it arises in pre‐existing benign eccrine spiradenoma. We report an additional case of malignant eccrine spiradenoma. The present case is of a 75‐year‐old man with malignant eccrine spiradenoma developed in the right shoulder. He had a 6‐year history of a recurrent mass that was removed 2 years ago. The patient then underwent a complete excision. The gross pathologic specimen showed a large cutaneous and subcutaneous multinodular tumor, measuring 6 cm in maximal dimension. Microscopically, there were two distinct morphological components: a benign eccrine spiradenoma and a malignant eccrine spiradenoma of low grade with extensive necrosis. Different histologic patterns were observed such as cylindromatous features. Morphological differentiation in malignant eccrine spiradenoma is variable, sometimes with almost complete loss of eccrine differentiation. Extensive sampling to look for a probable previously benign component is necessary. In the other hand, malignant changes can be easily missed without adequate sampling. Ben Brahim E, Sfia M, Tangour M, Makhlouf R, Cribier B, and Chatti S. Malignant eccrine spiradenoma: a new case report