Intradermal Band-like Lipomatous Metaplasia Can Be Associated With the Regression of Overlying Skin Neoplasms: A Clinicopathologic Study of 20 Cases.

ABSTRACT: Lipomatous metaplasia has been rarely reported in both neoplastic and inflammatory dermatological disorders. Most neoplastic cases show the lipomatous change within the tumor silhouette, but band-like lipomatous metaplasia in the dermis under tumors has not been well-described. The aim of this study was to reveal the characteristics and relationship of intradermal band-like lipomatous metaplasia and coexisting skin tumors. A total of 20 cases with intradermal band-like lipomatous metaplasia were retrieved from 10,992 archive cases between April 1997 and March 2020 at Hyogo Cancer Center, and subjected to a detailed clinicopathologic analysis. Nine (45%) patients had superficial variant basal cell carcinoma as a coexisting neoplasm. Eight (40%) patients had squamous cell carcinoma, 5 of which were in situ. The remaining 3 (15%) cases were invasive extramammary Paget disease. All 20 cases showed at least one of 3 signs of tumor regression, namely, partial loss of overlying neoplasia, significant inflammatory infiltrate under the tumor, and fibrosis around the tumor. We concluded that intradermal band-like lipomatous metaplasia could be seen in association with the regressing process of cutaneous superficially-spreading neoplasms.

Relationship between dermoscopy and pathology in a case of clonal-type pigmented Bowen's disease: Observation with vertical-view dermoscopy.

Pigmented Bowen's disease (pBD) is a subtype of Bowen's disease, which presents clinically as a well-circumscribed, hyperpigmented plaque. Its clinical manifestations are not fully characterized, and differential diagnoses include various pigmented skin lesions. Dermoscopy could be useful for the diagnosis, although nothing has been reported on the dermoscopic features of clonal-type pBD. We herein report a first case of clonal-type pBD on the sole and its dermoscopic features. Dermoscopy showed brown to blue-gray dots/globules and focally anastomosing lines on the non-weight-bearing area, while the weight-bearing area had a brown to blue-gray fibrillar-like pattern. To investigate the relationship between dermoscopy and histopathology, we focused on the melanin distribution in the horny layer of the epidermis, and used vertical dermoscopy observation. We investigated the relationship between dermoscopy and pathology by melanin depth estimation using a color lightness value.

A proposal for a TNM staging system for extramammary Paget disease: Retrospective analysis of 301 patients with invasive primary tumors.

BACKGROUND: Although extramammary Paget disease (EMPD) usually appears as carcinoma in situ, it sometimes becomes invasive (iEMPD) and fatal. However, a TNM staging system for iEMPD has yet to be established. OBJECTIVE: The aim of this study was to establish a TNM staging system for iEMPD. METHODS: We retrospectively collected iEMPD patients treated at 12 institutes in Japan. Factors reported to be associated with survival such as distant metastasis, lymph node (LN) metastasis, and primary tumor status were evaluated using the log-rank test. RESULTS: We enrolled 301 iEMPD patients, of whom 114 had remote metastases (49 had both distant and LN metastasis; 2, distant metastasis only; and 63, LN metastasis only) and the remaining 187 patients had no remote metastasis. Distant metastasis (M1) showed worse survival (P<0.00001). In the analysis of the 250 patients without distant metastasis, LN metastasis also showed worse survival (P<0.00001). Among the patients with LN metastasis, 2 or more LN metastases (N2) showed worse survival than did single LN metastasis (N1, P=0.02). Lastly, in the analysis of the 187 patients without metastasis, tumor thickness of over 4mm or lymphovascular invasion showed worse survival (T2, P<0.05 and P<0.001, respectively). Patients with neither of these features were defined as T1. From these results, we propose this TNM staging system: stage I, T1N0M0; stage II, T2N0M0; stage IIIa, anyTN1M0; stage IIIb, anyTN2M0; stage IV, anyTanyNM1. Other than stages II and IIIa, each stage had a statistically distinct survival curve. CONCLUSION: We propose a TNM staging system for EMPD using simple factors for classification that could provide important prognostic information in managing EMPD. However, accumulation of more patient data and further revision of the system are required.

CD117 (KIT) is a useful immunohistochemical marker for differentiating porocarcinoma from squamous cell carcinoma.

BACKGROUND: Distinguishing porocarcinoma from squamous cell carcinoma (SCC) is clinically significant but can pose a diagnostic dilemma. The present study sought to confirm the diagnostic utility of CD117 immunohistochemistry in distinguishing porocarcinoma from SCC and to examine histologic, carcinoembryonic antigen (CEA) immunohistochemical and CA19-9 immunohistochemical differences between these tumors. METHODS: Immunostaining with anti-CD117, anti-CEA and anti-CA19-9 antibodies was performed for 22 porocarcinomas and 31 SCCs. The extent of CD117, CEA and CA19-9 staining was classified as negative (<1%), rarely positive (1-4%), focally positive (5-29%) or diffusely positive (30-100%). CD117 staining intensity was semi-quantitatively graded as weak, moderate or strong. RESULTS: All (100%) porocarcinomas were positive for CD117, with mainly focal (8/22) or diffuse (11/22) and moderate (9/22) to strong (8/22) staining. In contrast, only 6 of 31 SCCs (19.4%) expressed CD117 focally, and this expression was limited to the basal layer of the tumor in four cases. CEA immunostaining highlighted the lumina of all 22 porocarcinomas; however, CEA expression was not significantly different between porocarcinomas and SCCs (100 vs. 71.0%, respectively). CA19-9 was not expressed in the lumina of 5 of 22 porocarcinomas. CONCLUSIONS: Along with CEA, CD117 immunohistochemistry could be helpful in distinguishing porocarcinomas from SCCs.

Usefulness of docetaxel as first-line chemotherapy for metastatic extramammary Paget's disease.

In invasive extramammary Paget's disease (EMPD), distant metastases may develop and the condition may become fatal; however, no standardized treatment has been established. Although based on only a few cases, several chemotherapy regimens were reported to be promising. We conducted a multicenter, retrospective study to evaluate the efficacy of docetaxel for metastatic EMPD. We retrospectively collected data on 18 metastatic EMPD patients treated using docetaxel from 1998 to 2012 in 12 institutes in Japan. The following clinical data were collected: tumor response, time to progression, overall survival and adverse effects. Of those, three patients treated combined with S-1, one patient treated with weekly schedule and one patient treated combined with radiotherapy were excluded from the further analysis. All 13 patients received monthly docetaxel as the first-line treatment. The average number of treatment cycles was 9.1. Among the 12 patients with a confirmed response, seven (58%) showed a partial response, three (25%) stable disease and two (17%) progressive disease. The disease control rate (partial response + stable disease) was as high as 83%. The time to progression and median overall survival were 7.1 and 16.6 months, respectively. The 1-year overall survival rate determined by the Kaplan-Meier method was 75.0%. All adverse effects were manageable and no treatment-related deaths were observed. The high disease control rate and overall survival shown by this study suggest that first-line use of docetaxel may be a promising treatment for metastatic EMPD. A prospective clinical trial is required to confirm our results.

The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients.

BACKGROUND: Although extramammary Paget's disease (EMPD) mostly presents as intraepithelial carcinoma, we sometimes encounter patients with invasive EMPD (iEMPD) who have lymph node metastasis and may develop distant metastasis. Although sentinel lymph node biopsy (SLNB) is widely accepted for various cancers, there is no large study that has assessed its role in iEMPD. OBJECTIVE: The main objective of this study is to assess the role of SLNB in patients with iEMPD. MATERIALS AND METHODS: We retrospectively collected data on 151 iEMPD patients treated from 1998 to 2012 in 11 institutes in Japan. All 151 patients received curative surgery for their primary tumor and none of them had distant metastasis. SLNB was performed on the 107 patients without lymphadenopathy to determine their LN status. The 44 other patients with lymphadenopathy underwent one of the following procedures to determine their LN status: SLNB in 22 cases, immediate LN dissection in 21, and LN biopsy in 1. RESULTS: Compared to those without lymphadenopathy, patients with lymphadenopathy had advanced primary tumors (nodule in the primary tumor, thicker tumor, deeper invasion level, and lymphovascular invasion). The rate of LN metastasis in patients with lymphadenopathy was 80%, compared to 15% in patients without lymphadenopathy who underwent SLNB. Compared to those with negative SLN, patients with positive SLN had advanced primary tumors (nodule in the primary tumor, deeper invasion level, and lymphovascular invasion). Multivariate analysis revealed that dermal invasion (odds ratio 5.8, p=0.04) and lymphovascular invasion (odds ratio 18.0, p=0.0023) were independent factors associated with SLN positivity. Notably, there was no difference in survival between patients with or without SLN metastasis (p=0.71). On the other hand, patients with lymphadenopathy showed worse survival than those with positive SLN (p=0.045). CONCLUSION: Clinical lymphadenopathy was strongly correlated with pathological LN metastasis and also associated with worse survival than absence of lymphadenopathy. The rate of occult LN metastasis detected by SLNB was 15%. Survival was not affected by SLN status even when an advanced primary tumor was present in patients with positive SLN. Our results raise the possibility that SLNB and subsequent LN dissection improved the survival of patients with early stage lymphatic spread. Our study indicates that SLNB should be considered for iEMPD if lymphadenopathy is not apparent.

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.

Case of tumor thrombus inside femoral vein, formed by melanoma metastasized to inguinal lymph node.

Inguinal lymph nodes are often excised in dermatological surgery, because they are the most common of the lymphatic basin involved in metastasis of malignant skin tumor on the lower extremities or genital region. Herein, we describe a case of cutaneous malignant melanoma on the buttock of a 78-year-old woman. Under the huge metastasized inguinal lymph node, there was tumor invasion into the femoral vein with intraluminal tumor thrombus formation. Careful preoperative radiological assessment enabled successful resection on surgery. A review of the published work revealed that tumor thrombus due to direct invasion of melanoma may be rare. The possibility of intravenous tumor thrombus should be considered in the settings of surgery of inguinal metastasis of melanoma, especially when a large-sized node is located near the great veins.

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.

Dots and lines: a dermoscopic sign of regression of longitudinal melanonychia in children.

It is not easy to predict the clinical course of longitudinal melanonychia (LM) in children because few prospective studies have been conducted. In our prospective study 15 Japanese children with LM were followed for more than 2 years. Eight patients demonstrated gradual fading of LM. Clinical features such as the patient's sex and the site, age of onset, duration, color, and width of the melanonychia were not significantly associated with the outcome. Dots distributed along melanotic lines, a finding we referred to as dots and lines, can be a dermoscopic sign of regression of melanonychia in children with LM. In this study, the presence of dermoscopically observed dots was significantly related with regression of melanonychia (P = .019; odds ratio, 18.0).