Shin‐Ichi Ansai

Schwannomas consist of both high‐cellularity regions (Antoni A area) and hypocellular regions (Antoni B area) in histopathological findings. Neurofibromas characteristically consist of CD34 positive spindle cells with thin, wavy, nuclei and wavy collagen bands. Previous reports have described segments of schwannomas with neurofibroma features as hybrid tumors, although hybrid tumors were diagnosed based on partial CD34 positivity in many previous reports. On the other hand, the Antoni B area of some schwannomas was reported to be positive for CD34. Therefore, the definition of a hybrid tumor has not been clear. The objective of this study was to determine whether only CD34 positive findings in schwannomas could be used to define a hybrid tumor. In the analysis of our patient with schwannomatosis caused by a novel LZTR1 germline mutation, part of the tumor had CD34 positive hypocellular regions. These regions contained no thin, wavy, nuclei, indicating an Antoni B area. Laser microdissection was used to investigate the genetic background and differences in molecular mechanisms between CD34 positive and CD34 negative regions. All mutations identified in CD34 positive regions were also found in CD34 negative regions. Our data could not clear the genetic background of Antoni B which was CD34 positive area. We then reviewed the pathologies of 66 sporadic schwannomas. Histopathological examinations of all schwannomas revealed the absence of thin, wavy, nuclei and wavy collagen bands, and no hybrid tumors were found in any of the cases. Ten of 66 patients were randomly selected for CD34 immunostaining and positivity was found in all cases. Our data suggest that it is difficult to distinguish schwannomas by staining for CD34 alone, as Antoni B areas can also be positive for CD34. Therefore, CD34 staining alone should not be used to diagnose hybrid tumors in patients with schwannomas.

Background: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs.Objective: To determine the potential for HCO‐ethoxylate‐containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO‐25, ‐40, ‐60 and ‐80).Animals: Four healthy male laboratory dogs.Materials and Methods: We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre‐treatment with an antihistamine.Results: All HCO‐ethoxylate‐containing drugs caused a wheal‐and‐flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO‐ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO‐60‐induced reaction was suppressed by an oral antihistamine.Conclusions and Clinical Relevance: The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision‐making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

Dermatofibroma is a common benign skin lesion with a contested etiology: some believe it is a neoplasm while others propose minor injuries initiate it. Many dermatofibroma variants have been described, including keloidal dermatofibroma, which is unusual by bearing keloidal collagen. Keloidal dermatofibroma was first described in 1998 and only 15 cases have been reported. Since keloids are driven by skin injuries, the existence of keloidal dermatofibroma has been suggested to support the injury hypothesis of dermatofibroma etiology. To better understand keloidal dermatofibroma characteristics and gain clues regarding dermatofibroma etiology, consecutive keloidal dermatofibroma cases (n = 52) and dermatofibroma without keloidal collagen (n = 2077) that were histopathologically diagnosed in 2016–2019 were identified from the records of a Japanese dermatopathology laboratory and compared in terms of demographic, clinical, and histopathological characteristics by univariate analyses. Compared to other dermatofibromas, keloidal dermatofibromas occurred more frequently on the forearm and hand (P < 0.0001 and 0.0019), especially the wrist dorsum, and in the superficial skin layer (P < 0.0001). Keloidal dermatofibromas also demonstrated more cellularity and hemorrhage (both P < 0.0001). Correlation analyses between keloidal collagen amount and keloidal dermatofibroma size (a proxy of time‐since‐onset) did not support the notion that keloidal collagen deposition and keloidal dermatofibroma formation are triggered simultaneously. Recent injury, as indicated by fresh hemorrhage, was equally common in putatively older and younger keloidal dermatofibromas. Thus, keloidal collagen in keloidal dermatofibromas could be due to injury to preexisting dermatofibromas, which suggests that the keloidal dermatofibroma entity does not prove the injury hypothesis. Commonalities between keloids and keloidal dermatofibromas suggest a link between genetics, provocative events that induce myofibroblast differentiation, and keloidal collagen production.

Cutaneous ossification is a rare, benign dermatological condition where bone forms in the dermis or subcutaneous tissue. It is classified as primary when it emerges without a pre-existing condition and secondary when it associates with an underlying condition such as trauma, scars, inflammation, and neoplastic disease. The secondary form accounts for most cases of cutaneous ossification. The pathogenesis of cutaneous ossification is not clear. Keloids are benign fibroproliferative skin disorders that are characterized by chronic inflammation. Their pathogenesis is also not fully understood. We report two cases of secondary ossification arising in postoperative lower abdominal keloids and review the literature on secondary ossification of the skin. We speculate that the intense chronic inflammation in keloids may drive the osteoblastic transformation of either mesenchymal stem cells, endothelial cells, or fibroblasts in the keloids.

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.

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.

In consideration of the development of treatment options for squamous cell carcinoma (SCC), the Japanese Skin Cancer Society issued the first guidelines of SCC in 2007 and revised them in 2015. Here, we report the English version of the 2020 edition of the Japanese SCC guidelines. The first half of this article is an overview of SCC including actinic keratosis and Bowen’s disease, and the second half discusses three clinical questions: (i) treatment of actinic keratosis; (ii) determination of the resection margin of the primary lesion; and (iii) treatment of radically incurable cases, as contemporary problems encountered in treating SCC. In these evaluations, all processes were implemented according to the Grading of Recommendations, Assessment, Development, Evaluation system. Also, items of recommendation concerning each clinical question were determined by a multidisciplinary expert panel consisting of dermatologists, plastic/reconstructive surgeons, radiologists, and oncologists through a comprehensive literature search and systematic reviews.

Pseudolymphomatous folliculitis (PLF) is a subtype of cutaneous pseudolymphoma that is recognized as an independent disease. PLF is characterized by dermal lymphocytic infiltration surrounding an irregular hyperplastic pilosebaceous unit (i.e., activated pilosebaceous unit). An interstitial distribution of CD1a‐positive cells is regarded as an important feature of PLF, especially in distinguishing it from primary cutaneous marginal zone lymphoma (PCMZL), which is associated with a peripheral concentration of CD1a‐positive cells. We undertook a clinicopathological investigation of PLF, with a reassessment of CD1a immunohistochemistry. We defined diagnostic criteria for PLF based on past studies and consequently identified 79 cases. In addition, we collected 32 cases of PCMZL and performed detailed clinical, pathological, and immunohistochemical investigations using antibodies to CD3, CD20, and CD1a. We found an interstitial concentration of CD1a‐positive cells in 90.2% of PLF and 34.5% of PCMZL cases. The peripheral concentration of CD1a‐positive cells was seen in 9.8% of PLF and 34.5% of PCMZL cases. In both diseases, CD1a‐positive cells appeared in T‐cell nests (88.5% in PLF and 92.9% in PCMZL) but were absent in B‐cell nests (0% in both groups). All 79 cases of PLF showed activated pilosebaceous units while 22 of the 32 PCMZL cases displayed pilosebaceous units, although none of these were activated. In summary, regarding the distribution patterns of CD1a‐positive cells as a diagnostic feature in distinguishing between PLF and PCMZL is somewhat inconclusive. To differentiate PLF and PCMZL, determining the presence or absence of activated pilosebaceous units is essential.