Crater/ulcerated form of infundibular squamous cell carcinoma: A possible distinct entity as a malignant (or high‐grade) counterpart to keratoacanthoma

Follicular squamous cell carcinoma (SCC) with infundibular differentiation includes the common and crater forms of infundibular SCC. We previously considered the crater/ulcerated infundibular SCC to be a progressive condition of the common form and histopathologically studied an additional five cases of the crater/ulcerated infundibular SCC, the results of which suggested the following characteristic histopathological features and possible developmental process in this type of SCC: (i) a considerable number of continuous hyperplastic follicular infundibula, which may develop at the beginning of the disease; (ii) hyperplastic infundibula exhibiting an abrupt or gradual transition to the SCC component, which frequently change relative to the neoplastic infundibular canal; and (iii) the presence of multiple sites of branching of the neoplastic infundibular canals and/or complete involvement of large cysts in the neoplastic process over the center of the lesion, resulting in ulceration. Based on these histopathological findings, we considered that crater/ulcerated infundibular SCC involve a considerable number of continuous follicular infundibula from the start, although some cases may develop from the common form. We also emphasize the possible aggressive biological behavior of the crater/ulcerated form. Keratoacanthoma (KA) is a unique, benign or borderline malignant neoplasm exhibiting follicular (infundibular/isthmic) differentiation characterized by the involvement of continuous follicular infundibula in multiples. From this standpoint, we consider that crater/ulcerated infundibular SCC is possibly related to KA in terms of histogenesis and is a malignant (or high‐grade) counterpart of KA.     

角化棘皮瘤和皮肤鳞状细胞癌bcl—2和Nm23癌基因蛋白表达的比较研究

目的：通过研究分析bcl-2和Nm23蛋白在角化棘皮瘤（KA）和皮肤鳞状细胞癌（SCC）中的表达和临床意义。探寻两病的鉴别标志。方法：应用免疫组化技术（SABC）对11例KA，28例SCC进行了检测。结果：bcl-2和Nm23蛋白在KA和SCC中的表达经统计学分析无显著性意义。结论：bcl-2和Nm23癌基因均参与了KA和SCC的发病过程，但都不能作为KA和SCC的鉴别标志。     

角化棘皮瘤与高分化鳞状细胞癌细胞凋亡及凋亡基因bcl-2和bax比较研究

目的：探讨角化棘皮瘤与皮肤高分化鳞癌在细胞凋亡方面的差异。方法：用脱氧核苷酰转移酶介导的ｄ－ＵＴＰ生物素缺口末端标记技术,原位检测了ＫＡ和ｗＳＣＣ的凋亡细胞。用免疫组化研究技术研究了皮损部位与细胞凋亡有关ｂａｘ和ｂｃｌ－２的基因产物的表达。结果：凋亡细胞在ＫＡ发生率为８０％;在ｗＳＣＣ也为８０％。     

PD-L1在皮肤鳞状细胞癌及角化棘皮瘤中的表达

目的：检测PD-L1在皮肤鳞状细胞癌（cSCC）及角化棘皮瘤（KA）中的表达,分析PD-L1与cSCC分化程度的相关性。方法：免疫组化染色检测PD-L1在cSCC及KA中表达水平。结果：共检测56例cSCC患者和32例KA患者标本，PD-L1在cSCC组和KA组中的阳性率分别为66.07%和62.50%，均显著高于正常对照组（9.38%）（Ps＜0.01）。PD-L1阳性率在cSCC与KA组的差异没有统计学意义（P＞0.05）。PD-L1的表达强度与cSCC的分化程度呈负相关（P＜0.05）。结论：PD-L1不能作为区分cSCC与KA的指标。PD-L1的表达强度与cSCC分化程度呈负相关。     

Keratoacanthoma and other types of squamous cell carcinoma with crateriform architecture: Classification and identification

The terminology and classification of keratoacanthoma (KA) and other types of squamous cell carcinoma (SCC) with crateriform architecture have not been clarified. The study evaluated the clinicopathological features of 41 nodular (exo‐endophytic) SCC lesions with a central keratin‐filled crater, including KA (well‐developed stage). The lesions were histopathologically classified into six categories: (i) KA (well‐developed stage) (27 lesions); (ii) KA‐like SCC (three lesions); (iii) KA with malignant transformation (three lesions); (iv) infundibular SCC (crateriform) (four lesions); (v) crateriform SCC arisen from actinic keratosis (three lesions); and (vi) crateriform Bowen's disease (one lesion). The true characteristics of KA‐like SCC remain unresolved, but there are three possibilities, namely, that it is one step in the evolution of KA, it is a borderline lesion between KA and invasive SCC, or it is one form of “KA with malignant transformation”. KA, KA‐like SCC, KA with malignant transformation and infundibular SCC (crater form) are considered to be hair follicle‐related neoplasms. In contrast, crateriform SCC arisen from actinic keratosis and crateriform Bowen's disease are SCC, which are not related either to the hair follicles or KA. From an etiological standpoint, the presented lesions in these six categories are considered to be mixed up due to the similarity of crateriform architecture between the various types of lesions. However, the information provided in this report is intended to help physicians to make an accurate differential diagnosis of these conditions in clinical practice. The present study provides an opportunity to standardize the terminology for KA and related neoplasms.     

Two cases of squamous cell carcinoma treated with topical imiquimod 5%

We report the first two cases of squamous cell carcinoma successfully treated with imiquimod 5% cream as a monotherapy. Imiquimod is a new immunomodulating drug that is registered for genital HPV infection but has also shown good efficacy in several cutaneous malignancies.     

Treatment of multiple lesions of Bowen's disease and squamous cell carcinoma with topical imiquimod

We observed complete clinical and histopathologic remission of papules, plaques and nodules in two patients with multiple lesions of Bowen's disease and squamous cell carcinoma. Our findings indicate that topical imiquimod is a potentially promising therapeutic approach for the local treatment of early forms of cutaneous neoplasia, such as Bowen's disease and squamous cell carcinoma because it is a non-invasive therapy with a good cosmetic outcome. It may therefore be worthy of consideration in a subgroup of patients who cannot have or do not wish to have surgery.     

Recurrent keratoacanthoma with vascular invasion: A diagnostic and management dilemma

A 71-year-old man with chronic renal failure and on peritoneal dialysis presented with recurrence of multiple keratotic nodules along a surgical scar. This was 6 months after the excision of a recurrent keratotic nodule reported as squamous cell carcinoma from the same site. The lesions were initially reported as squamous cell carcinomas, but on review of histology were consistent with keratoacanthomas. One of the keratoacanthomas showed vascular invasion. These responded well to low-dose acitretin at 10 mg three times per week and the patient stayed in remission after 18 months of follow up.     

Cases with a spontaneous regression of an infiltrating non‐crateriform keratoacanthoma and squamous cell carcinoma with a keratoacanthoma‐like component

We herein report the natural course of an early/proliferative stage keratoacanthoma (KA) with infiltrating islands of cytological malignancy (case 1) and a squamous cell carcinoma (SCC) with a KA‐like component (case 2), which were observed until their complete regression. The presented case 1 suggests that one of the histopathological forms of KA includes this unusual, infiltrating, non‐crateriform architecture, and also indicates the possibility of complete remission in the KA associated with infiltrating islands of cytological malignancy. In the presented case 2, the peripherally‐associated KA‐like focus was histopathologically considered to be either a remnant of KA focus or verrucous keratosis (hyperplasia). Therefore, the complete spontaneous regression of case 2 suggests that SCC arising in KA still has the potential of spontaneous regression, or that an extremely rare event, namely, the spontaneous regression of (traditional) SCC occurred in the present case.     

Treatment of verrucous carcinoma of vulva with acitretin

We describe a 60-year-old patient with verrucous carcinoma of the vulva, which recurred 6 years after simple vulvectomy and radiotherapy. Treatment with acitretin led to significant improvement and ongoing disease control has been achieved with low-dose maintenance therapy of 10 mg acitretin daily.     

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.     

EGFR and MYC gene copy number aberrations are more common in squamous cell carcinoma than keratoacanthoma: a FISH study

Epidermal growth factor receptor (EGFR) and MYC genomic aberrations have been described in cutaneous squamous cell carcinoma (SCC) but have not been widely investigated in keratoacanthoma (KA). EGFR and MYC were evaluated by fluorescence in situ hybridization and immunohistochemistry in 8 verrucae, 19 involuting KA (IKA), 23 classic KA (CKA), 6 atypical KA (AKA) and 19 SCC. Increased EGFR gene copy number was seen in 9 of 23 CKA and 14 of 19 SCC (p = 0.03). Increased MYC gene copy number was observed in 7 of 23 CKA and 17 of 19 SCC (p = 0.0001). MYC gene amplification was more common in SCC than CKA (p = 0.005), while EGFR gene amplification was rare and not significant. MYC protein overexpression was identified in 6 of 23 CKA and 14 of 19 SCC (p = 0.005). There was no statistical difference in EGFR protein overexpression in SCC and CKA (p = 0.06). EGFR and MYC aberrations were rare in IKA. AKA showed EGFR and MYC anomalies at an incidence intermediate between CKA and SCC. EGFR and MYC gene copy number aberrations are more common in SCC than KA. The incidence of aberrations parallels the degree of cytologic atypia in KA.     

Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod

Pembrolizumab, a humanized monoclonal antibody against programmed cell death 1, is used for various malignant neoplasms. Toll‐like receptor (TLR) agonists, specifically targeting the TLR9 subfamily (TLR7–9), are treatment options for solid tumors and hematological malignancies. We experienced a case of eruptive squamous cell carcinoma (SCC) in a patient treated concomitantly with pembrolizumab and imiquimod, a TLR7 agonist. A 75‐year‐old woman who was given a diagnosis of bladder cancer with lung metastasis received pembrolizumab for 3 months when she was referred to our department for the evaluation of skin rashes on her hands. Her skin lesions were diagnosed as well‐differentiated SCC and treated with topical imiquimod. Two months after the start of imiquimod, more than 10 reddish papules appeared on her hands. The histological diagnosis of a new plaque was the same as an earlier biopsy. We herein describe this case in detail and provide a published work review.     

Possible spontaneous regression of a metastatic lesion of keratoacanthoma-like squamous cell carcinoma in a regional lymph node

We report herein a case of keratoacanthoma-like squamous cell carcinoma in an 82-year-old male that showed regional lymph node metastasis followed by self-regression of the metastatic lesion. This case is consistent with the previously reported observation that tumors compatible with the clinical features of keratoacanthoma may have malignant biological potential, however, it also demonstrates that even metastatic lesions may exhibit self-regression similar to that observed for primary lesions. Despite the view that keratoacanthoma-like squamous cell carcinoma may represent a variant of squamous cell carcinoma, occasionally it undergoes a unique clinical course.     

In situ photoimmunotherapy is ineffective in treating deeply invasive squamous cell carcinoma

In situ photoimmunotherapy (ISPI) can be a treatment option for selected cutaneous malignancies in patients who are not surgical candidates. We herein report the case of a large, ulcerating poorly differentiated squamous cell carcinoma (SCC) affecting the foot of an elderly woman with chronic arsenicosis. The tumor failed radiotherapy, intralesional methotrexate, and 5-aminolevulinic acid photodynamic therapy (PDT). Because the patient was reluctant to undergo amputation, the recurrent tumor was treated with ISPI using topical imiquimod application followed by PDT. Despite some initial improvement in the superficial part of the tumor, tumor invasion to the underlying bone was detected. This case illustrates the lack of efficacy of ISIP in treating a high-risk invasive SCC.     

Natural course of keratoacanthoma and related lesions after partial biopsy: Clinical analysis of 66 lesions

There is some confusion regarding the classification of keratoacanthoma (KA) and related lesions that have crateriform architecture. We examined the clinical courses of 66 KA lesions and related lesions after a partial biopsy to clarify the nosological concept of KA. We histopathologically classified these lesions into five types: (i) KA at various stages (53 lesions); (ii) KA‐like squamous cell carcinoma (SCC) (3 lesions); (iii) KA with malignant transformation (3 lesions); (iv) infundibular SCC (5 lesions); and (v) crateriform SCC arising from solar keratosis (2 lesions). We analyzed the clinical course in each group. The regression rate of KA was 98.1% and that of KA‐like SCC/KA with malignant transformation was 33.3%. No regression was observed in either infundibular SCC or crateriform SCC arising from solar keratosis. Thus, KA is a distinct entity that should be distinguished from other types of SCC with crateriform architecture based on the high frequency of regression. The regression rate of 33.3% in KA‐like SCC/KA with malignant transformation indicated that KA lesions with an SCC component still have the potential for regression. However, this result also indicated that KA is biologically unstable, and some KA tend to evolve into conventional SCC with a gradual loss of the capacity for the spontaneous regression. Infundibular SCC and crateriform SCC arising from solar keratosis are fundamentally different from KA, not only according to the histopathological findings but also based on the biological properties.     

角化棘皮瘤和鳞状细胞癌P21和P53蛋白表达的比较研究

目的：通过检测Ｐ＾２１和Ｐ＾５３蛋白在角化棘皮瘤（ＫＡ）和磷状细胞癌（ＳＣＣ）中的表达,探讨两病之间的关系。方法：用免疫组化技术检测１１例ＫＡ和２８例ＳＣＣ皮损部位Ｐ＾２１和Ｐ＾５３蛋白的表达。结果：Ｐ＾２１蛋白在ＫＡ和ＳＣＣⅠ－Ⅱ中的表达密度分级有统计学意义（Ｐ＝０．０２）。Ｐ＾５３在两病的表达无统计学差异。结论：Ｐ＾２１和Ｐ＾５３在ＫＡ和ＳＣＣ中表达的异同不能作为ＫＡ和ＳＣＣ的鉴别诊断指标。     

Merkel细胞癌合并原位鳞状细胞癌一例并文献复习

Merkel细胞癌是一种罕见的、具有高度侵袭性的皮肤神经内分泌癌,好发于老年人的日光暴露部位,尤其是头颈部(41%～50%),其次是四肢(32%～38%)。Merkel细胞癌可与鳞状细胞癌、鲍温病、基底细胞癌等皮肤肿瘤合并发生。我们报道一例发生在非光暴露部位的Merkel细胞癌合并原位鳞状细胞癌,并对相关文献进行复习。