Epithelial pearls and Keratin pearls are pathognomonic of squamous cell carcinoma. However, their histogenesis is not well understood. Only a handful of studies have been conducted in the past in this regard. This brief communication aims to understand the formation of these pearls with a few of our own experiences.

Squamous cell carcinoma (SCC) is one of the most common forms of skin cancer in humans, and Neural Wiskott-Aldrich Syndrome Protein (N-WASP) plays a crucial role in epidermal homeostasis. To elucidate the role of N-WASP in skin cancer, we generated mice which expressed constitutively active KRas (KRasG12D) in keratinocytes with either homozygous (N-WASPKOG12D) or heterozygous (N-WASPHetG12D) N-WASP knockout upon Tamoxifen (TAM) injection. Both the N-WASPKOG12D and N-WASPHetG12D mice had similar body weights and no congenital malformations prior to the injection of TAM. Within 2 weeks of the injections, the N-WASPKOG12D mice exhibited significant reductions in weight coupled with visible tumors at numerous sites, unlike the N-WASPHetG12D mice, which had no visible tumors. We found that both sets of mice had oily, sticky skin and wet eyes 3 weeks after their exposure to TAM, indicating the overproduction of sebum/meibum. At 37 days post TAM injection, several notable observations were made. Tumors collected from the N-WASPKOG12D mice had small- to large-sized keratin pearls that were not observed in the N-WASPHetG12D mice. A Western blot and immunostaining analysis both highlighted significantly higher levels of expression of SCC markers, such as the cytokeratins 8, 17, 18, and 19 and TP63, in the tumors of the N-WASPKOG12D mice compared to those of the latter group. Furthermore, we noted increases in the expression levels of EGFR, P-ERK, GLUT1, P-mTOR, and P-4EBP in the N-WASPKOG12D mice, suggesting that the deletion of N-WASP in the keratinocytes enhanced KRas signaling and glucose uptake, resulting in aggressive tumor formation. Interestingly, a thickening of the epidermal layer within the esophagus and tongue was only observed in the N-WASPKOG12D mice. Immunostaining for PCNA emphasized a significantly higher number of PCNA-positive cells in the skin of the N-WASPKOG12D mice compared to their counterparts, implying that epidermal thickening and enhanced tumorigenesis are due to an increased proliferation of keratinocytes. Through our results, we have established that N-WASP plays a tumor-suppressive role in skin cancer.

BACKGROUND: Keratin pearls are intraepithelial accumulations of squamous cells and debris that can be an etiology of vulvovaginal irritation in pediatric patients and are often associated with clitoral adhesions. Historically, most cases have been managed with manual or operative lysis of adhesions.
METHODS: Two prepubertal girls presented to our clinic with chronic clitoral irritation and were found to have clitoral adhesions with keratin pearls. Both were managed with topical estrogen cream, which resulted in resolution of their symptoms.
CONCLUSIONS: Keratin pearls can form when the overlying clitoral epithelium becomes blocked by clitoral adhesions. Hypoestrogenism is thought to be implicated in adhesion development; thus, topical estrogen cream is a reasonable option in initial management. Our results demonstrate a noninvasive alternative to the initial treatment of clitoral keratin pearls.

Reptiles are popular exotic pets and green iguanas (Iguana iguana) are amongst the top ten most popular reptiles. Here we describe a captive 8-year-old female green iguana that was referred for treatment of a non-healing, discharging lesion on the side of the body. The lesion was surgically excised and histopathological analysis revealed an epidermal proliferation of neoplastic keratinocytes, with focal infiltration through the basement membrane, into the underlying superficial dermis. Marked dysplastic changes, characterized by multifocal dyskeratosis and keratin pearl formation were also noted. A diagnosis of cutaneous squamous cell carcinoma (SCC) was made. Two years later, the iguana has shown no signs of recurrence. This is the first report of successful treatment of cutaneous SCC in a green iguana and contributes to the limited knowledge of cutaneous neoplasms in green iguanas.

Identification of various constituent layers such as epithelial, subepithelial, and keratin of oral mucosa and characterization of keratin pearls within keratin region as well, are the important and mandatory tasks for clinicians during the diagnosis of different stages in oral cancer (such as precancerous and cancerous). The architectural variations of epithelial layers and the presence of keratin pearls, which can be observed in microscopic images, are the key visual features in oral cancer diagnosis. The computer aided tool doing the same identification task would certainly provide crucial aid to clinicians for evaluation of histological images during diagnosis. In this paper, a two-stage approach is proposed for computing oral histology images, where 12-layered (7 × 7×3 channel patches) deep convolution neural network (CNN) are used for segmentation of constituent layers in the first stage and in the second stage the keratin pearls are detected from the segmented keratin regions using texture-based feature (Gabor filter) trained random forests. The performance of the proposed computing algorithm is tested in our developed oral cancer microscopic image database. The proposed texture-based random forest classifier has achieved 96.88% detection accuracy for detection of keratin pearls.

暂无摘要。

Oral squamous cell carcinoma (OSCC) has contributed 90% of oral cancer worldwide. In situ histological evaluation of tissue sections is the gold standard for oral cancer detection. Formation of keratinization and keratin pearl is one of the most important histological features for OSCC grading. This paper aims at developing a computer assisted quantitative microscopic methodology for automated identification of keratinization and keratin pearl area from in situ oral histological images. The proposed methodology includes colour space transform in YDbDr channel, enhancement of keratinized area in most significant bit (MSB) plane of Db component, segmentation of keratinized area using Chan-Vese model. The proposed methodology achieves 95.08% segmentation accuracy in comparison with (manually) experts-based ground truths. In addition, a grading index describing keratinization area is explored for grading OSCC cases (poorly, moderately and well differentiated).

Hsp90α (heat shock protein 90α), one of the important molecular chaperones in cancer cell signal transduction, has been a new candidate target for cancer therapy. Cyclin B1, the client protein of Hsp90α, plays a key role as a mitotic cyclin in the G2-M phase transition during the cell cycle progression. However, the relationship between the level of HSP90α and cyclin B1, the location of Hsp90α and cyclin B1 in prognosis of esophageal squamous cell carcinoma (ESCC) has not been examined. Here, we demonstrate that the diagnostic significance of Hsp90α and cyclin B1 by immunohistochemistry and the association of Hsp90α and cyclin B1 expression in ESCC. In the specimens from 105 ESCC patients (81 stained with Hsp90α antibody by Immunohistochemistry, 65 with cyclin B1 antibody, and among them, 41 paired specimens were stained with Hsp90α and cyclin B1 respectively, and then checked for the correlation of the level and location of Hsp90α and cylcin B1. The positivity rate of Hsp90α and cyclin B1 expression were 96.3% (78 of 81) and 84.6% (55 of 65) respectively. Both of them, the expression levels are associated with the clinical pathological stage (Hsp90α, p=0.027; cyclin B1, p=0.007). No association was found between Hsp90α or cyclin B1 and gender, age, tumor location. As to TMN stage, there is no association with the level of Hsp90α, However, cyclin B1 expression is significantly related to tumor status (p=0.002). Interestingly, Hsp90α expression was negatively correlated to cyclin B1 expression (Gamma=-0.692, p=0.007) in the keratin pearls though there is a positive correlation in the other areas of tumor (Gamma=0.503, p=0.015), which suggest Hsp90α might play diverse roles in the cyclin B1 expression and cyclin B1 related cell cycle regulation in the different area of tumor. These findings demonstrated that the expression of Hsp90α, cyclin B1 protein is associated with tumor malignancy and prognosis for patients with human esophageal squamous cell carcinoma, and Hsp90α might be involved in cyclin B1 expression regulation and cell cycle regulation in keratin peal formation of ESCC.