Advances in Diagnostic Dermatopathology, from Histopathologic to Molecular Studies

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 59110

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Guest Editor
Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Aichi 470-1192, Japan
Interests: anatomic pathology (surgical pathology); clinical pathology (laboratory medicine); immunopathology (particularly B-cell immunity); glycobiology (particularly carbohydrate addressin)

Special Issue Information

Dear Colleagues,

Dermatopathology is the most sophisticated area in anatomic pathology; we can easily observe superficial skin lesions using our eyes without the need for an invasive approach and can easily compare gross configurations to microscopic findings. Meanwhile, dermatopathology has recently focused on the study of various cutaneous diseases at molecular biology level. Additionally, dozens and dozens of cutaneous diseases are now being well-researched—melanocytic nevus and malignant melanoma, psoriasis, pemphigus, allergic dermatitis, autoimmune diseases, skin infections, and so on.

Here, we invite investigators such as dermatologists and pathologists to contribute original research articles as well as review articles that reveal novel findings of diagnostic dermatopathology such as diagnosable new morphological (histopathologic) findings, immunohistochemical and immunofluorescent markers, and molecular techniques. We also invite articles that discuss prognostic examinable factors in skin tumors and intractable dermatitis. Relevant case reports will be warmly acknowledged.

Dr. Yasuhiro Sakai
Guest Editor

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Keywords

  • Dermatopathology
  • Histopathologic findings
  • Immunohistochemical markers
  • Molecular studies

Published Papers (11 papers)

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Editorial

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2 pages, 179 KiB  
Editorial
The Philosophy of Dermatopathology
by Yasuhiro Sakai
Diagnostics 2022, 12(12), 3091; https://doi.org/10.3390/diagnostics12123091 - 08 Dec 2022
Viewed by 739
Abstract
Diagnostic pathology involves studying sample cells and tissues obtained from the specific lesions of interest [...] Full article

Research

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16 pages, 3654 KiB  
Article
PSORS1 Locus Genotyping Profile in Psoriasis: A Pilot Case-Control Study
by Noha Z. Tawfik, Hoda Y. Abdallah, Ranya Hassan, Alaa Hosny, Dina E. Ghanem, Aya Adel and Mona A. Atwa
Diagnostics 2022, 12(5), 1035; https://doi.org/10.3390/diagnostics12051035 - 20 Apr 2022
Cited by 4 | Viewed by 2134
Abstract
(1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, [...] Read more.
(1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, rs10484554 within LOC105375015 gene, were investigated and correlated with psoriasis risk and severity. (2) Methods: This pilot case-controlled study involved 100 psoriatic patients and 100 healthy individuals. We investigated three SNPs and assessed the relative gene expression profile for the PSORS1C1 gene. We then correlated the results with both disease risk and severity. (3) Results: The most significantly associated SNP in PSORS1 locus with psoriasis was rs10484554 with its C/T genotype 5.63 times more likely to develop psoriasis under codominant comparison. Furthermore, C/T and T/T genotypes were 5 times more likely to develop psoriasis. The T allele was 3 times more likely to develop psoriasis under allelic comparison. The relative gene expression of PSORS1C1 for psoriatic patients showed to be under-expressed compared to normal controls. (4) Conclusions: Our study revealed the association of the three studied SNPs with psoriasis risk and severity in an Egyptian cohort, indicating that rs10484554 could be the major key player in the PSORS1 locus. Full article
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9 pages, 1146 KiB  
Article
STAT3 Activation in Psoriasis and Cancers
by Megumi Kishimoto, Mayumi Komine, Miho Sashikawa-Kimura, Tuba Musarrat Ansary, Koji Kamiya, Junichi Sugai, Makiko Mieno, Hirotoshi Kawata, Ryutaro Sekimoto, Noriyoshi Fukushima and Mamitaro Ohtsuki
Diagnostics 2021, 11(10), 1903; https://doi.org/10.3390/diagnostics11101903 - 15 Oct 2021
Cited by 9 | Viewed by 1571
Abstract
Activation of signal transducer and activator of transcription (STAT)3 has been reported in many cancers. It is also well known that STAT3 is activated in skin lesions of psoriasis, a chronic skin disease. In this study, to ascertain whether patients with psoriasis have [...] Read more.
Activation of signal transducer and activator of transcription (STAT)3 has been reported in many cancers. It is also well known that STAT3 is activated in skin lesions of psoriasis, a chronic skin disease. In this study, to ascertain whether patients with psoriasis have a predisposition to STAT3 activation, we examined phosphorylated STAT3 in cancer cells of psoriasis patients via immunohistochemistry. We selected patients with psoriasis who visited the Department of Dermatology, Jichi Medical University Hospital, from January 2000 to May 2015, and had a history of cancer. We performed immunostaining for phosphorylated STAT3 in tumor cells of five, four, and six cases of gastric, lung, and head and neck cancer, respectively. The results showed that there was no significant difference in STAT3 activation in any of the three cancer types between the psoriasis and control groups. Although this study presents limitations in its sample size and inconsistency in the histology and differentiation of the cancers, results suggest that psoriasis patients do not have a predisposition to STAT3 activation. Instead, STAT3 activation is intricately regulated by each disorder or cellular microenvironment in both cancer and psoriasis. Full article
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14 pages, 4352 KiB  
Article
Mechanical Intermittent Compression Affects the Progression Rate of Malignant Melanoma Cells in a Cycle Period-Dependent Manner
by Takashi Morikura and Shogo Miyata
Diagnostics 2021, 11(6), 1112; https://doi.org/10.3390/diagnostics11061112 - 18 Jun 2021
Cited by 4 | Viewed by 2264
Abstract
Static mechanical compression is a biomechanical factor that affects the progression of melanoma cells. However, little is known about how dynamic mechanical compression affects the progression of melanoma cells. In the present study, we show that mechanical intermittent compression affects the progression rate [...] Read more.
Static mechanical compression is a biomechanical factor that affects the progression of melanoma cells. However, little is known about how dynamic mechanical compression affects the progression of melanoma cells. In the present study, we show that mechanical intermittent compression affects the progression rate of malignant melanoma cells in a cycle period-dependent manner. Our results suggest that intermittent compression with a cycle of 2 h on/2 h off could suppress the progression rate of melanoma cells by suppressing the elongation of F-actin filaments and mRNA expression levels related to collagen degradation. In contrast, intermittent compression with a cycle of 4 h on/4 h off could promote the progression rate of melanoma cells by promoting cell proliferation and mRNA expression levels related to collagen degradation. Mechanical intermittent compression could therefore affect the progression rate of malignant melanoma cells in a cycle period-dependent manner. Our results contribute to a deeper understanding of the physiological responses of melanoma cells to dynamic mechanical compression. Full article
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9 pages, 3459 KiB  
Article
A Positive Dermcidin Expression Is an Unfavorable Prognostic Marker for Extramammary Paget’s Disease
by Shun Ohmori, Yu Sawada, Natsuko Saito-Sasaki, Sayaka Sato, Yoko Minokawa, Hitomi Sugino, Hikaru Nanamori, Kayo Yamamoto, Etsuko Okada and Motonobu Nakamura
Diagnostics 2021, 11(6), 1086; https://doi.org/10.3390/diagnostics11061086 - 14 Jun 2021
Cited by 1 | Viewed by 1959
Abstract
Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great [...] Read more.
Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease. Full article
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Review

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13 pages, 20038 KiB  
Review
Lichen Sclerosus: A Current Landscape of Autoimmune and Genetic Interplay
by Noritaka Oyama and Minoru Hasegawa
Diagnostics 2022, 12(12), 3070; https://doi.org/10.3390/diagnostics12123070 - 06 Dec 2022
Cited by 5 | Viewed by 27463
Abstract
Lichen sclerosus (LS) is an acquired chronic inflammatory dermatosis predominantly affecting the anogenital area with recalcitrant itching and soreness. Progressive or persistent LS may cause urinary and sexual disturbances and an increased risk of local skin malignancy with a prevalence of up to [...] Read more.
Lichen sclerosus (LS) is an acquired chronic inflammatory dermatosis predominantly affecting the anogenital area with recalcitrant itching and soreness. Progressive or persistent LS may cause urinary and sexual disturbances and an increased risk of local skin malignancy with a prevalence of up to 11%. Investigations on lipoid proteinosis, an autosomal recessive genodermatosis caused by loss-of-function mutations in the extracellular matrix protein 1 (ECM1) gene, led to the discovery of a humoral autoimmune response to the identical molecule in LS, providing evidence for an autoimmune and genetic counterpart targeting ECM1. This paper provides an overview of the fundamental importance and current issue of better understanding the immunopathology attributed to ECM1 in LS. Furthermore, we highlight the pleiotropic action of ECM1 in homeostatic and structural maintenance of skin biology as well as in a variety of human disorders possibly associated with impaired or gained ECM1 function, including the inflammatory bowel disease ulcerative colitis, Th2 cell-dependent airway allergies, T-cell and B-cell activation, and the demyelinating central nervous system disease multiple sclerosis, to facilitate sharing the concept as a plausible therapeutic target of this attractive molecule. Full article
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22 pages, 792 KiB  
Review
Epidermolysis Bullosa—A Different Genetic Approach in Correlation with Genetic Heterogeneity
by Monica-Cristina Pânzaru, Lavinia Caba, Laura Florea, Elena Emanuela Braha and Eusebiu Vlad Gorduza
Diagnostics 2022, 12(6), 1325; https://doi.org/10.3390/diagnostics12061325 - 27 May 2022
Cited by 9 | Viewed by 3132
Abstract
Epidermolysis bullosa is a heterogeneous group of rare genetic disorders characterized by mucocutaneous fragility and blister formation after minor friction or trauma. There are four major epidermolysis bullosa types based on the ultrastructural level of tissue cleavage: simplex, junctional, dystrophic, and Kindler epidermolysis [...] Read more.
Epidermolysis bullosa is a heterogeneous group of rare genetic disorders characterized by mucocutaneous fragility and blister formation after minor friction or trauma. There are four major epidermolysis bullosa types based on the ultrastructural level of tissue cleavage: simplex, junctional, dystrophic, and Kindler epidermolysis bullosa. They are caused by mutations in genes that encode the proteins that are part of the hemidesmosomes and focal adhesion complex. Some of these disorders can be associated with extracutaneous manifestations, which are sometimes fatal. They are inherited in an autosomal recessive or autosomal dominant manner. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in epidermolysis bullosa, and on the correlation genotype–phenotype. Full article
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16 pages, 1084 KiB  
Review
The Pathology of Type 2 Inflammation-Associated Itch in Atopic Dermatitis
by Catharina Sagita Moniaga, Mitsutoshi Tominaga and Kenji Takamori
Diagnostics 2021, 11(11), 2090; https://doi.org/10.3390/diagnostics11112090 - 12 Nov 2021
Cited by 14 | Viewed by 2921
Abstract
Accumulated evidence on type 2 inflammation-associated itch in atopic dermatitis has recently been reported. Crosstalk between the immune and nervous systems (neuroimmune interactions) is prominent in atopic dermatitis research, particularly regarding itch and inflammation. A comprehensive understanding of bidirectional neuroimmune interactions will provide [...] Read more.
Accumulated evidence on type 2 inflammation-associated itch in atopic dermatitis has recently been reported. Crosstalk between the immune and nervous systems (neuroimmune interactions) is prominent in atopic dermatitis research, particularly regarding itch and inflammation. A comprehensive understanding of bidirectional neuroimmune interactions will provide insights into the pathogenesis of itch and its treatment. There is currently no agreed cure for itch in atopic dermatitis; however, increasing numbers of novel and targeted biologic agents have potential for its management and are in the advanced stages of clinical trials. In this review, we summarize and discuss advances in our understanding of type 2 inflammation-associated itch and implications for its management and treatment in patients with atopic dermatitis. Full article
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13 pages, 13409 KiB  
Review
What Is a Solitary Keratoacanthoma? A Benign Follicular Neoplasm, Frequently Associated with Squamous Cell Carcinoma
by Azusa Ogita and Shin-ichi Ansai
Diagnostics 2021, 11(10), 1848; https://doi.org/10.3390/diagnostics11101848 - 07 Oct 2021
Cited by 5 | Viewed by 3691
Abstract
We present histopathological criteria for diagnosing keratoacanthoma (KA). In KA, four histological stages are recognized, which are the early/proliferative stage, well-developed stage, regressing stage and regressed stage. In diagnosing KA, we emphasize that KA consists of the proliferation of enlarged pale pink cells [...] Read more.
We present histopathological criteria for diagnosing keratoacanthoma (KA). In KA, four histological stages are recognized, which are the early/proliferative stage, well-developed stage, regressing stage and regressed stage. In diagnosing KA, we emphasize that KA consists of the proliferation of enlarged pale pink cells with ground glass-like cytoplasm without nuclear atypia, other than crateriform architecture. KA sometimes exhibits malignant transformation within the lesions. We describe the characteristics of benign and malignant epithelial crateriform tumors that should be differentiated from KA. We also present the data of histopathological diagnosis of lesions clinically diagnosed as KA, its natural course and related lesions after partial biopsy, and incidence of crateriform epithelial neoplasms. Based on these data, we recommend complete excision of the lesion when KA is clinically suspected, especially when the lesion is located on a sun-exposed area of an elderly patient. If complete excision is impossible, partial excision of a sufficient specimen with intact architecture is required. In such a case, however, careful investigation after biopsy will be needed, even if the histopathological diagnosis is KA, because there is some possibility that a conventional SCC lesion remains in the residual tissue. Full article
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9 pages, 1238 KiB  
Review
Diagnosis of Early Mycosis Fungoides
by Tomomitsu Miyagaki
Diagnostics 2021, 11(9), 1721; https://doi.org/10.3390/diagnostics11091721 - 19 Sep 2021
Cited by 14 | Viewed by 9587
Abstract
Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphomas, generally has a favorable clinical course. Early MF typically presents erythematous patches and/or plaques and lasts for many years without affecting the life expectancy. Only limited cases progress to develop skin tumors, [...] Read more.
Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphomas, generally has a favorable clinical course. Early MF typically presents erythematous patches and/or plaques and lasts for many years without affecting the life expectancy. Only limited cases progress to develop skin tumors, with subsequent lymph nodes and rarely visceral organ involvement. One of the clinical problems in early MF is the difficulty in differentiating the disease from benign inflammatory disorders (BIDs), such as atopic dermatitis, chronic eczema, and psoriasis. In some MF cases, clinical and pathological findings are similar to those of BIDs. However, the accurate diagnosis of early MF is quite important, as inappropriate treatment including immunosuppressants can cause unfavorable or even fatal outcomes. This article focuses on general methods and novel tools for diagnosis of early MF. Full article
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Other

3 pages, 8232 KiB  
Interesting Images
Secondary Malignant Tumors Arising in Nevus Sebaceus: Two Case Reports
by Sohshi Morimura, Yasuhiko Tomita, Shinichi Ansai and Makoto Sugaya
Diagnostics 2022, 12(6), 1448; https://doi.org/10.3390/diagnostics12061448 - 13 Jun 2022
Viewed by 1561
Abstract
Nevus sebaceus is a benign tumor that is present at birth and is often seen on the scalp or face. Secondary malignant tumors sometimes occur in nevus sebaceus in adulthood. Herein, we present two malignant tumors arose from nevus sebaceus. One is basal [...] Read more.
Nevus sebaceus is a benign tumor that is present at birth and is often seen on the scalp or face. Secondary malignant tumors sometimes occur in nevus sebaceus in adulthood. Herein, we present two malignant tumors arose from nevus sebaceus. One is basal cell carcinoma on the face and the other is sebaceus carcinoma on the lower back, where nevus sebaceus rarely occurs. Basal cell carcinoma sometimes develops in sebaceus nevus after a few decades, seen usually on the scalp or face. Sebaceus carcinoma is a rare malignant tumor that arises in nevus sebaceus. Full article
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