Apocrine Differentiation Research Articles

Cryotherapy as a method of choice in the treatment of cylindromas on the elderly

<p>The elderly (i.e., geriatric group) are often vulnerable to skin cancer. These patients often cannot cope with biopsies and surgical excisions. A good alternative is cryotherapy. Cylindroma is a benign adnexal tumor of the skin with eccrine and apocrine differentiation, and commonly occurs in the scalp. We present the case of an 82- year-old woman with a number of large tumors located on the head, which were effectively removed via cryotherapy with liquid nitrogen as a palliative treatment. No recurrence was detected during the two-year follow-up. Cryotherapy with liquid nitrogen is an effective and non-invasive method for the treatment of benign skin tumors in the elderly.</p>

Papillary adnexal neoplasm (aggressive digital papillary adenocarcinoma) on the ankle of a 15‐year‐old girl: case report and review of literature from a pediatric perspective

Digital papillary adenocarcinoma is a rare malignant tumor of the sweat glands, most commonly encountered in adult males. Only few pediatric cases have been reported, with an apparent predominance of females and none on the ankle. We report a case of a 15-year-old girl with a slowly growing, non-tender mass on the right ankle presenting with difficulty in walking; clinically believed to be a keloid. Excision of the mass revealed a glandular neoplasm with largely eccrine and focally apocrine differentiation. Histologic features do not reliably predict biologic behavior. Because of the existing confusion over the nomenclature, we propose that such tumors be called 'papillary adnexal neoplasms of distal extremities'.

Clinicopathological analysis of 384 cases of poroid neoplasms including 98 cases of apocrine type cases.

We examined 384 cases of poroid neoplasms. Most cases (n = 279, 72.7%) exhibited the features of only one subtype. One hundred and ninety-eight cases (51.6%) showed only the features of poroma (P), 20 (5.2%) hidroacanthoma simplex (HS), five (1.3%) dermal duct tumor (D) and 56 (14.6%) hidradenoma (HA). Composite tumors of those four subtypes were observed in 105 cases (27.3%). In the trunk and lower extremities, lesions with the features of P were observed at higher rates than other sites. Those of HS and D were more frequently observed in the lower extremities. Those of HA were seen at higher rates in the scalp, face, neck and genitalia. Ninety-eight cases (25.5%) showed decapitation secretion and diagnosed as apocrine type lesion. Apocrine type lesions were frequently observed in the lesions on the genitalia (40.0%), scalp (31.8%) and trunk (31.1%), whereas at lower rates in those on the neck (21.4%) and lower extremities (24.0%). In apocrine type cases, the lesions were located more frequently on the scalp and trunk than non-apocrine type, whereas were less frequent on extremities. The rate of apocrine type lesions in the cases with only one subtype (19.7%) was lower than that of those with composite tumors (41.0%). In the apocrine type (43.9%), composite tumors are more frequent than in the non-apocrine type (21.7%). In D (40.8%) and HA (32.3%), apocrine type lesions were more frequently observed than other subtypes. In conclusion, it should be noted that a quarter of poroid neoplasms are composite tumors and/or show apocrine differentiation.

A cellular model reflecting the phenotypic heterogeneity of mutant HRAS driven squamous cell carcinoma.

Squamous cell carcinomas have a range of histopathological manifestations. The parameters that determine this clinically observed heterogeneity are not fully understood. Here, we report the generation of a cell culture model that reflects part of this heterogeneity. We have used the catalytic subunit of human telomerase hTERT and large T to immortalize primary UV-unexposed keratinocytes. Then, mutant HRAS G12V has been introduced to transform these immortal keratinocytes. When injected into immunosuppressed mice, transformed cells grew as xenografts with distinct histopathological characteristics. We observed three major tissue architectures: solid, sarcomatoid and cystic growth types, which were primarily composed of pleomorphic and basaloid cells but in some cases displayed focal apocrine differentiation. We demonstrate that the cells generated represent different stages of skin cancerogenesis and as such can be used to identify novel tumor-promoting alterations such as the overexpression of the PADI2 oncogene in solid-type SCC. Importantly, the cultured cells maintain the characteristics from the xenograft they were derived from while being amenable to manipulation and analysis. The availability of cell lines representing different clinical manifestations opens a new tool to study the stochastic and deterministic factors that cause case-to-case heterogeneity despite departing from the same set of oncogenes and the same genetic background.

Genetic alterations of triple negative breast cancer by targeted next-generation sequencing and correlation with tumor morphology

Triple negative breast cancer represents a heterogeneous group of breast carcinomas, both at the histologic and genetic level. Although recent molecular studies have comprehensively characterized the genetic landscape of these tumors, few have integrated a detailed histologic examination into the analysis. In this study, we defined the genetic alterations in 39 triple negative breast cancers using a high-depth targeted massively parallel sequencing assay and correlated the findings with a detailed morphologic analysis. We obtained representative frozen tissue of primary triple negative breast cancers from patients treated at our institution between 2002 and 2010. We characterized tumors according to their histologic subtype and morphologic features. DNA was extracted from paired frozen primary tumor and normal tissue samples and was subjected to a targeted massively parallel sequencing platform comprising 229 cancer-associated genes common across all experiments. The average number of non-synonymous mutations was 3 (range 0–10) per case. The most frequent somatic alterations were mutations in TP53 (74%) and PIK3CA (10%) and MYC amplifications (26%). Triple negative breast cancers with apocrine differentiation less frequently harbored TP53 mutations (25%) and MYC gains (0%), and displayed a high mutation frequency in PIK3CA and other PI3K signaling pathway-related genes (75%). Using a targeted massively parallel sequencing platform, we identified the key somatic genetic alterations previously reported in triple negative breast cancers. Furthermore, our findings show that triple negative breast cancers with apocrine differentiation constitute a distinct subset, characterized by a high frequency of PI3K pathway alterations similar to luminal subtypes of breast cancer.

Overexpression of MYB drives proliferation of CYLD-defective cylindroma cells.

Cutaneous cylindroma is an adnexal tumour with apocrine differentiation. A predisposition to multiple cylindromas is seen in patients with Brooke–Spiegler syndrome, who carry germline mutations in the tumour suppressor gene CYLD. Previous studies of inherited cylindromas have highlighted the frequent presence of bi‐allelic truncating CYLD mutations as a recurrent driver mutation. We have previously shown that sporadic cylindromas express either MYB–NFIB fusion transcripts or show evidence of MYB activation in the absence of such fusions. Here, we investigated inherited cylindromas from several families with germline CYLD mutations for the presence of MYB activation. Strikingly, none of the inherited CYLD‐defective (n = 23) tumours expressed MYB–NFIB fusion transcripts. However, MYB expression was increased in the majority of tumours (69%) and global gene expression analysis revealed that well‐established MYB target genes were up‐regulated in CYLD‐defective tumours. Moreover, knock‐down of MYB expression caused a significant reduction in cylindroma cell proliferation, suggesting that MYB is also a key player and oncogenic driver in inherited cylindromas. Taken together, our findings suggest molecular heterogeneity in the pathogenesis of sporadic and inherited cutaneous cylindromas, with convergence on MYB activation. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

A case report of invasive ductal carcinoma of the breast with prominent sebaceous differentiation

Background Sebaceous carcinoma of the breast is a rare entity, with only nine examples reported previously (WHO, 2012). Sebaceous carcinoma is defined as a breast carcinoma with prominent sebaceous differentiation in no less than 50% of cells (WHO, 2012). Limited data is available regarding the significance of sebaceous differentiation. Aim To present a case of diagnostic interest. Method and results We present a case of a 77-year-old woman with a self-detected left breast mass. After an initial core biopsy she underwent a mastectomy with sentinel lymph node biopsy. His-topathology confirmed an ER-positive/PR-positive/Her2-equiv-ocal invasive ductal carcinoma, with prominent sebaceous differentiation, and negative sentinel nodes. Discussion The amount of sebaceous differentiation falls just short of the greater than 50% required for diagnosis of sebaceous carcinoma. The differential diagnosis includes carcinoma with apocrine differentiation, lipid-rich carcinoma, and liposarcoma. A review of the available literature highlights the scarcity of knowledge of this rare entity. Very little is understood about the clinical course and prognosis of sebaceous carcinoma, and follow up data is limited. There is an association in the cases reported, with high grade tumours and high mitotic counts, and the predominant type of breast cancer associated is ductal. The two cases that have reported metastasis have been late in onset, and have occurred in sites which are not common for breast malignancies (scalp and skin). The significance of sebaceous differentiation is difficult to establish, and further research is warranted.

Syringocystadenoma Papilliferum of External Auditory Canal: A Rare Entity

ABSTRACT Syringocystadenoma papilliferum is a benign adnexal tumor that frequently shows apocrine differentiation. It has propensity to develop in the scalp region. It is a rare tumor and usually appears at birth or during puberty, hence, it is also called childhood tumor. Although it may differ in clinical presentation, its histology is characteristic. In this study, we have described the syringocystadenoma papilliferum in the external auditory canal of a 45-year-old female because of its occurrence in an unusual site and in an uncommon age. How to cite this article Kumar S, Singh HP, Singh AK. Syringocystadenoma Papilliferum of External Auditory Canal: A Rare Entity. Int J Head Neck Surg 2016;7(4):223-224.

Uroplakin II Expression in Breast Carcinomas Showing Apocrine Differentiation: Putting Some Emphasis on Invasive Pleomorphic Lobular Carcinoma as a Potential Mimic of Urothelial Carcinoma at Metastatic Sites.

Uroplakin II antibody is exclusively specific for urothelial carcinoma. Nonurothelial carcinoma has not been reported to be immunoreactive for uroplakin II. In the present study, we hypothesized that breast carcinoma showing apocrine differentiation, such as invasive pleomorphic lobular carcinoma (IPLC) and apocrine carcinoma (AC), stains positive for uroplakin II. We identified 6 cases of IPLC between 2000 and 2014 by searching a computerized pathological database. We randomly selected 10 cases of each classic invasive lobular carcinoma (cILC) and AC and five cases of apocrine metaplasia (AM) that coexisted in a surgically resected breast carcinoma specimen. Immunohistochemistry was performed for uroplakin II, GATA3, CK7, CK20, and other representative markers positive for urothelial carcinoma. All cases of IPLC, AC, and AM, except those of cILC, showed immunoreactivity for uroplakin II. Poorly differentiated urothelial carcinoma sometimes shows similar morphology to IPLC with the following immunophenotype: CK7+, CK20−, GATA3+, and uroplakin II+. In the present study, this immunophenotype was observed in all the cases of IPLC and AC. Therefore, when studying metastatic, poorly differentiated carcinoma showing the aforementioned immunophenotype, we should consider the possibility of it being IPLC in addition to metastatic urothelial carcinoma.

Expression of high affinity folate receptor in breast cancer brain metastasis.

High affinity folate receptor (HFR) can be overexpressed in breast cancer and is associated with poor prognosis, however the expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the rate of HFR expression in BCBM and its role in the prognosis of this high-risk cohort. We analyzed 19 brain metastasis (BM) and 13 primary tumors (PT) from a total of 25 patients. HFR status was assessed by immunohistochemistry. Median follow-up was 4.2 years (range 0.6-18.5). HFR was positive in 4/19 BM (21.1%) and in 1/13 PT (7.7%). Positive samples had low H-scores (range 1-50). 56% of patients had apocrine differentiation. OS was similar between patients with positive HFR (median OS 48 months) and negative HFR (median OS 69 months) (P = 0.25); and between patients with apocrine differentiation (median OS 63 months) and those without apocrine differentiation (median OS 69 months) (P = 0.49). To the best of our knowledge, this is the first analysis of HFR expression in BCBM. While previous studies associated the presence of HFR with worse prognosis; in our cohort HFR was positive in only 21.1% of BM with low levels of positivity. Neither HFR nor apocrine features had impact in OS.

Abstract P6-01-15: Expression of high affinity folate receptor in breast cancer brain metastasis

Abstract Background: Folic acid is required by proliferating cells for the synthesis of nucleotide bases among other tasks. The high affinity folate receptor (HFR) is a membrane protein that is upregulated in several cancers of epithelial origin and rarely present in most normal cells. High expression of HFR has been documented in ovarian, breast, kidney, uterine and lung cancers. In breast cancer patients, HFR is overexpressed in 33% of primary tumors (PT) and this is associated with poor prognosis. The HFR expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the incidence of HFR expression in BCBM and its role in the prognosis of this high-risk patient subgroup. Methods: We analyzed a database of 42 patients who underwent craniotomy with resection of breast cancer brain metastasis (BCBM). Of those, we collected 19 brain metastasis (BM) and 13 PT. HFR status was assessed by immunohistochemistry. Log-Rank test analyzed differences in overall survival (OS) between groups. Results: Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). HFR was positive in 4/19 BM (21.1%) and in 1/13 PT (7.7%). Positive samples had low H-scores (range 1-50). Staining with H&E revealed that 11/19 BM (57.9%) and 7/13 PT (53.8%) had apocrine differentiation. Analysis of OS showed no difference between patients with positive HFR (median OS 48 months) and negative HFR (median OS 69 months) (P=0.25). Similarly, there was no difference in OS between patients with apocrine differentiation (median OS 63 months) and those without apocrine differentiation (median OS 69 months) (P=0.49). Conclusions: To the best of our knowledge, this is the first analysis of HFR expression in BCBM. While previous studies associated the presence of HFR with worse prognosis; in this cohort of high-risk patients, HFR was positive in only 21.1% of BM with low levels of positivity. Around half of our patients had apocrine differentiation. Neither the status of HFR nor the presence of apocrine features had impact in OS in our cohort. Citation Format: Jose P Leone, Rohit Bhargava, Adrian Lee, Adam Brufsky. Expression of high affinity folate receptor in breast cancer brain metastasis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-15.

Spectrum of skin adnexal tumors with eccrineand apocrine differentiation – A single institution study of 40 cases with clinicopathological correlation

Background: Adnexal skin tumors are relatively rare and present diagnostic difficulties in view of the endless morphological spectrum, complex nomenclature and incomplete knowledge of their histogenesis. Since pathologists encounter these lesions rarely, accurate sub classification of these can be challenging. This study intends to study skin adnexal tumors with eccrine and apocrine differentiation with emphasis on their histomorphology.Materials and Methods:The present study is a five year retrospective study with comprehensive analysis of 40 cases of adnexal tumors of skin in a tertiary center in Karnataka, South India. These tumors were reclassified and subtyped according to WHO classification of skin tumors, 2006.Results and analysis:Out the 62 cases of adnexal tumors studied, 40 were tumors with eccrine and apocrine differentiation (77% benign and 23% malignant). Hidradenoma was the most common tumor comprising 37% of all tumors and 45% of the benign tumors followed byspiradenoma, cylindroma and chondroidsyringoma respectively. Head and neck region was the most common site of occurrence, and seventh decade was the most frequent age group of presentation. A definite female preponderance was noted. Pagets disease of the breast was the most common malignant tumor in this group comprising (10%). Conclusion: Histopathology is considered the gold standard in the diagnosis of these tumors and so a clear knowledge of the clinical presentation and histomorphology of these tumors is essential to make a correct diagnosis. A diagnostic logarithm based on histomorphology provides a logical approach in the subclassification of adnexal tumors.DOI:

Cornoid Lamellation Revisited

Porokeratosis is a family of several disorders characterized histologically by the presence of cornoid lamellae. The presence of cornoid lamellae represents an abnormal form of keratinization, which unifies all types of porokeratosis. A significant variation in lesional morphology can result from peculiarities involving the cornoid lamellae and changes related to epidermal hyperplasia and dermal inflammation. This diversity has led to the recognition of several unusual clinicopathological variants of porokeratosis in recent years. Cornoid lamellation, however, is not pathognomonic of porokeratosis and can be seen in some inflammatory and inherited cutaneous disorders and also as an incidental finding. Some of these conditions can be confused with an atypical presentation of porokeratosis and vice versa. An awareness of the broad morphological spectrum of porokeratosis is crucial to avoid missing the diagnosis when appearances are far from typical. This issue is critical in patient management given the potential premalignant nature of porokeratosis.

Tubular apocrine adenoma

Tubular apocrine adenoma, the apocrine variant of papillary tubulopapillary hidradenoma is a rare well-circumscribed, intradermal benign tumor, with tubular structures showing apocrine differentiation. We present a 40 year female with swelling on the scalp of one year duration measuring 3 x 3.5 x 2 cm. On gross examination, a 2 x 2 x 1.5 cm grayish white mass was seen. H and E stained sections from the tumor mass revealed tubules of various sizes lined by two layers of cells, an outer cuboidal and inner columnar. Some of the tubules showed intraluminal papillary projections without a fibrovascular core. Diagnosis of tubular apocrine adenoma was made. Tubular apocrine adenoma is an unusual entity which may be mistaken for other adnexal tumors both clinically and cytologically. Histopathologic examination is essential for diagnosis.

FABP7 and HMGCS2 are novel protein markers for apocrine differentiation categorizing apocrine carcinoma of the breast.

Apocrine carcinoma of the breast is a distinctive malignancy with unique morphological and molecular features, generally characterized by being negative for estrogen and progesterone receptors, and thus not electable for endocrine therapy. Despite the fact that they are morphologically distinct from other breast lesions, no standard molecular criteria are currently available for their diagnosis. Using gel-based proteomics in combination with mass spectrometry and immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that categorize the entire breast apocrine differentiation spectrum from benign metaplasia and cysts to invasive stages. Expression of HMGCS2 and FABP7 is strongly associated with apocrine differentiation; their expression is retained by most invasive apocrine carcinomas (IAC) showing positive immunoreactivity in 100% and 78% of apocrine carcinomas, respectively, as compared to non-apocrine tumors (16.7% and 6.8%). The nuclear localization of FABP7 in tumor cells was shown to be associated with more aggressive stages of apocrine carcinomas. In addition, when added to the panel of apocrine biomarkers previously reported by our group: 15-PGDH, HMGCR and ACSM1, together they provide a signature that may represent a golden molecular standard for defining the apocrine phenotype in the breast. Moreover, we show that combining HMGCS2 to the steroidal profile (HMGCS2+/Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)- identifies IACs with a greater sensitivity (79%) as compared with the steroidal profile (AR+/ER-/PR-) alone (54%). We have also presented a detailed immunohistochemical analysis of breast apocrine lesions with a panel of antibodies against proteins which correspond to 10 genes selected from published transcriptomic signatures that currently characterize molecular apocrine subtype and shown that except for melanophilin that is overexpressed in benign apocrine lesions, these proteins were not specific for morphological apocrine differentiation in breast.

Superficial Soft Tissue Biphasic Synovial Sarcoma With Apocrine Differentiation in the Glandular Component

: The authors present 2 cases of a subcutaneous biphasic synovial sarcoma with marked apocrine differentiation that potentially may be confused with cutaneous epithelial neoplasms, including malignant apocrine mixed tumor or metaplastic carcinoma with an apocrine glandular component. Microscopically, both neoplasms had a biphasic architecture with the epithelial and spindle cell components. The epithelial component was prominent and consisted of simple glands with round lumina and complex glandular structures with intraluminal bridges forming cribriform areas. The glands were lined by cuboidal to columnar cells with eosinophilic or clear cytoplasm manifesting apical apocrine-like and intraluminal eosinophilic secretions. The spindle cell component was less prominent and was composed of relatively uniform or slightly atypical spindle sells surrounding and merging focally with the glandular structures. Immunohistochemically, the tumor cells in both components were positive for vimentin, AE1/AE3, CK7, and epithelial membrane antigen. Desmin, smooth muscle actin, muscle-specific actin, CD34, and S-100 protein were all negative. SYT-SSX1 gene fusion using fluorescence in situ hybridization and RT-PCR methods was detected in both cases.

Carcinomas with Apocrine Differentiation: Comparison of Clinicopathologic Features with Invasive Breast Carcinoma of No Special Type (NST) in Turkish Patients

Carcinomas with Apocrine Differentiation: Comparison of Clinicopathologic Features with Invasive Breast Carcinoma of No Special Type (NST) in Turkish Patients

Syringocystadenoma papilliferum (deep seated horiostomatous): a case report

Syringocystadenoma papilliferum (SCAP) is a rare benign adenexal tumor that frequently shows apocrine differentiation. SCAP usually occurs in the head and neck region in the children. Here in we report a case of 22 years female with SCAP occurring in deeper portion of the neck. The clinical, histopathological features and differential diagnosis of SCAP are also described. DOI: http://dx.doi.org/10.3126/jucms.v2i1.10491 Journal of Universal College of Medical Sciences (2014) Vol.2(1): 38-40

Syringocystadenocarcinoma Papilliferum In Situ

Syringocystadenocarcinoma papilliferum (SCACP) is an extremely rare cutaneous neoplasm with apocrine differentiation. Only 27 cases have been reported up-to-date, 8 of them described as carcinomas in situ. Two cases with local recurrence and 3 cases with regional lymph node metastases have been documented. The authors present the case of a 32-year-old female with a SCACP in situ on the scalp that recurred 8 years after the excision of the primary tumor. No SCACP with late recurrence have been previously reported. This case highlights the need for a long-term follow-up in patients with this type of carcinoma.

Cutaneous spread of primary neuroendocrine breast carcinoma with apocrine differentiation

Cutaneous spread of primary neuroendocrine breast carcinoma with apocrine differentiation