Survival of patients with basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ: A whole population study.

BACKGROUND: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood. OBJECTIVES: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders. METHODS: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015. RESULTS: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis. CONCLUSION: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups.

The utility of p63, CK7, and CAM5.2 staining in differentiating pagetoid intraepidermal carcinomas.

BACKGROUND: Extramammary Paget disease (EMPD), pagetoid squamous cell carcinoma in situ (PSCCIS), and Paget disease of the breast (PD) are intraepidermal carcinomas with overlapping histopathologic features. CK7 and CAM5.2 stains are frequently utilized to distinguish PSCCIS from EMPD and PD. However, some cases of PSCCIS can stain positively for CAM5.2 and CK7, indicating a potential pitfall with these stains. p63 has been shown to distinguish PSCCIS from EMPD. We assessed p63 staining in PD and compared it to p63 staining of PSCCIS and EMPD. METHODS: A retrospective search for 15 examples each of PSCCIS, EMPD, and PD with remaining tissue in the paraffin block was performed. The diagnosis was confirmed by a board-certified dermatopathologist and immunostaining for p63, CK7, and CAM5.2 was performed. Staining >55% was scored as positive. Staining <55% was scored as negative and an approximate percentage of positive cells was recorded. RESULTS: Diffuse nuclear expression for p63 was detected in 100% (15/15) of PSCCIS cases, 0% (0/15) of PD cases, and 0% (0/15) of EMPD cases. CK7 and CAM5.2 stains were positive in 100% of PD. CAM5.2 was positive in 100% of EMPD and CK7 was positive in 93% of EMPD. CAM5.2 was positive in 0% of PSCCIS biopsy specimens, but partial staining was seen in 20%. CK7 was positive in 13%, but partial staining was seen in 47%. CONCLUSIONS: p63 immunostaining is a highly sensitive and specific method for differentiating between PSCCIS and PD or EMPD. While CAM5.2 and CK7 are also useful ancillary stains in this differential diagnosis, false-positive and false-negative staining occurs with these two markers.

Bladder squamous cell carcinoma in situ in the background of condyloma acuminatum in a kidney transplant recipient.

Condyloma acuminatum with synchronous squamous cell carcinoma in situ (CIS) rarely occurs in the bladder. In developed countries, bladder squamous cell carcinoma (SCC) is uncommon. Among the various noninvasive squamous bladder lesions, there is significant morphological overlap, which further complicates accurate diagnosis. Immunosuppression and human papilloma virus increase the risk of bladder condyloma acuminatum, which has a strong association with bladder SCC. Herein, we describe a case of a 79-year-old man with a history of end-stage renal disease with kidney transplantation and anal SCC who presented with bladder squamous cell CIS arising in the background of condyloma acuminatum.

Squamous Cell Carcinoma in Situ of the Nail Unit: Current Evidence and Recommendations for Patient Centered Treatment.

Squamous cell carcinoma in situ of the hand and nail is an infrequent tumor but represents the majority of hand and nail malignancies. While the conventional treatments of invasive nail unit squamous cell carcinoma include Mohs micrographic surgery, wide local excision, or distal digit amputation, no standardized management paradigm for in situ disease exists and the necessity of surgical options is debated. This review aims to discuss the most commonly reported treatment methods and critically assess relevant management considerations in order to facilitate appropriate treatment decisions for nail unit SCCis across dermatologic practice settings. Assessment of the current literature reveals insufficient evidence to determine a standardized treatment for nail unit squamous cell carcinoma in situ. Rather, management is greatly impacted by multiple factors including the presence of subungual involvement, surgical candidacy, importance of curative treatment, and patient preferences regarding cosmesis and function versus cure. When cure is desired, Mohs micrographic surgery is the treatment of choice in most cases. In the setting of desired curative intent, but poor surgical candidacy, radiotherapy may be effective and provide a reasonable chance of functional and cosmetic preservation. Other methods including photodynamic therapy, electrodesiccation and curettage, cryotherapy, and intralesional chemotherapeutics may be appropriate in specific circumstances, but are generally limited by lack of evidence or impracticalities. Lastly, observation with palliation may be appropriate when considering exceedingly rare disease-related mortality.

A case of coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ of the cervix.

Poorly differentiated adenosquamous carcinoma (glassy cell carcinoma) of the cervix is extremely rare, accounting for 1-2% of all cervical cancers. Herein, we report a case with coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), "usual-type" adenocarcinoma, and squamous cell carcinoma in situ of the cervix. A female patient in her 60 s was referred to our hospital and diagnosed with poorly differentiated adenosquamous carcinoma based on cervical cytology and biopsy. The tumor was classified as clinical stage IB1 cervical cancer following magnetic resonance imaging; radical hysterectomy was performed. Histopathological examination revealed poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ, all coexisting. All carcinoma regions showed identical sizes to high-risk human papillomavirus (HPV) in fragment analysis. The patient is currently alive, without evidence of recurrence, 31 months post surgery. In this case, three different carcinomas coexisted. Fragment analysis of the patient's HPV status suggested that all carcinomas were related to an infection with the same high-risk HPV type. To determine the precise mechanism of tumor development, i.e., whether the tumors were of the mixed or collision type, further studies are needed, including clonal analysis for the loss of heterozygosity pattern.

Efficacy of nonexcisional treatment modalities for superficially invasive and in situ squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Squamous cell carcinoma in situ (SCCIS) and squamous cell carcinoma (SCC) are prevalent conditions that are increasing in incidence worldwide. Many nonexcisional treatments are commonly used, but the efficacy of these treatments has not been well delineated. OBJECTIVES: To examine the recurrence rates of SCCIS and SCC treated with nonexcisional treatment modalities. METHODS: A systematic review and meta-analysis were performed for SCCIS and SCC treated with 5-fluorouracil, imiquimod, electrodessication, curettage, photodynamic therapy, ablative lasers, or cryotherapy. RESULTS: We included 186 studies describing the treatment of 9336 tumors. The recurrence rates of SCC and SCCIS following electrodessication with curettage (2.0%; 95% CI, 1.1-3.0) or following cryotherapy with curettage (1.6%; 95% CI, 0.4-2.8) were lower than those of SCC and SCCIS managed with other treatments, such as photodynamic therapy (29.0%; 95% CI, 25.0-33.0), 5-fluorouracil (26.6%; 95% CI, 16.9-36.4), or imiquimod (16.1%; 95% CI, 10.3-21.8). LIMITATIONS: The limitations included a publication bias in mostly observational data and heterogeneity of treatment regimens. CONCLUSIONS: Electrodessication and cryotherapy, in combination with curettage, are more effective than photodynamic therapy, 5-fluorouracil, or imiquimod in treating SCCIS and SCC.

Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland.

BACKGROUND: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. OBJECTIVES: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. METHODS: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). LIMITATIONS: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. CONCLUSION: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies.

Photodynamic therapy for cutaneous squamous cell carcinoma in situ: Impact of anatomic location, tumor diameter, and incubation time on effectiveness.

BACKGROUND: Photodynamic therapy (PDT) has been reported as a treatment for cutaneous squamous cell carcinoma in situ (SCCis), but only limited data are available on the effectiveness of PDT with aminolevulinic acid (ALA-PDT). OBJECTIVE: To review the outcomes of SCCis treated with ALA-PDT and examine factors associated with response. METHODS: A retrospective review identified 58 patients with 68 primary SCCis lesions treated with ALA-PDT and blue light illumination. Patient demographics, lesion features, treatment details, clinical response, and subsequent recurrence were extracted from medical record reviews. RESULTS: On completion of PDT the initial complete response rate was 77.9% and was not associated with the number of PDT treatments. On multivariate analysis factors associated with response were location on the face, tumor diameter <2 cm, and longer ALA incubation time. Lesions treated with a maximum incubation time of <3 hours had a 53.3% response compared with 84.9% for longer incubation. Subsequent recurrence of SCCis was noted in 7 of 53 cases (13.2%) at a median time of 11.7 months. LIMITATIONS: This was a retrospective study performed at a single institution without systematic follow-up. CONCLUSIONS: ALA-PDT may be an effective treatment for selected cases of SCCis. Effectiveness is impacted by anatomic location, tumor diameter, and ALA incubation time.

Bowen disease with matrical differentiation: Report of an exceptional histopathologic presentation.

Matrical differentiation is the distinctive feature of pilomatricoma and other purely matrical adnexal neoplasms; additionally, foci of matrical differentiation have been also described in hybrid cysts of Gardner syndrome, as well as in a wide variety of benign and malignant cutaneous tumors, including basal cell carcinoma. We report an exceptional case of Bowen disease exhibiting multiple foci of matrical differentiation, as confirmed by means of immunohistochemical studies. Several types of divergent, non-squamous differentiation have been exceptionally reported in cutaneous squamous cell carcinoma in situ (cSCCIS), including sebaceous, mucinous/glandular, poroid, tricholemmal, and neuroendocrine differentiation; matrical differentiation may be added to this list. Our findings further emphasize the undifferentiated nature of neoplastic cells in cSCCIS.

Risk Factors and Prognosis for Metastatic Cutaneous Squamous Cell Carcinoma: A Cohort Study.

Cutaneous squamous cell carcinoma (cSCC) has metastatic potential. The aims of this study were to identify the risk factors for metastasis of primary cSCC and for poor prognosis in metastatic cSCC. Retrospective primary tumour cohorts of metastatic cSCCs (n = 85) and non-metastatic cSCCs (n = 218) were analysed. The mean annual rate of metastasis for primary cSCCs was 2.28%. In 49.4% of patients with metastatic cSCC, metastasis was detected within 6 months of diagnosis of the primary cSCC. There was no prior history of cSCC in 84.7% of metastatic cSCCs. Risk factors for metastasis included Clark's level 5, tumour diameter 20-29.9 mm, age at diagnosis < 50 or 70-79 years, and location on lower lip or forehead. A reduced risk of metastasis correlated with: isosorbide mono-/di-nitrate and/or aspirin use; comorbidity with actinic keratosis or basal cell carcinoma; and actinic keratosis or cSCC in situ as part of, or confirmedly preceding, primary cSCC. Poor prognosis in metastatic cSCC correlated significantly with ≥3 nodal metastases and extranodal extension of metastasis. These results characterize new risk factors for metastatic cSCC.

A rare case of Bowen's disease of the nipple: Literature review and management pathway.

INTRODUCTION: Bowen's disease or squamous cell carcinoma in situ is a precursor malignant neoplasm restricted to the epidermis. Clinically and histologically, Bowen's disease of the nipple can resemble Paget's disease. It is crucial to differentiate between the two with immunohistological staining in order to provide the appropriate treatment. This review of Bowen's disease of the nipple will examine the diagnostic and treatment modalities previously used. We also present our own case of Bowen's disease of the nipple and propose a clinical pathway for this rare disease process. METHODS: A review of published literature using MEDLINE, PubMed, and Google Scholar revealed seven articles were identified with a total of eight cases of Bowen's disease of the nipple. RESULTS: Treatment modalities varied within the literature. This ranged from photodynamic therapy to simple mastectomy and sentinel lymph node biopsy. Standard surgical margins are inadequate for Bowen's disease of the nipple, as it has been shown to spread along the lactiferous ducts. Our case is of a 57-year-old female with Bowen's disease of her right nipple, confirmed through immunohistological staining. Wide local excision with immediate full-thickness skin graft reconstruction was performed and is now disease-free with a healed graft. CONCLUSION: There is no accepted management pathway for Bowen's disease of the nipple. We propose a treatment algorithm that involves immunohistological staining to diagnose Bowen's disease of the nipple. This would then be followed by a wide local excision, complete nipple excision including underlying lactiferous ducts and glandular tissue and subsequent reconstruction.

Photodynamic therapy: A targeted literature review focussing on outcomes and optimisation in solid organ transplant recipients.

Squamous cell carcinoma incidence is 65- to 250-fold in solid organ transplant recipients, BCC is 10-fold and in Australia, rates of skin cancer in solid organ transplant recipients reach 70-82% prevalence within the first 20 years; hence, effective, evidence-based treatment of early and precancerous lesions is an essential tool in dermatological patient care. Photodynamic therapy is used to treat a range of conditions including actinic keratoses, squamous cell carcinoma in situ, superficial basal cell carcinoma and nodular basal cell carcinoma. A literature review was undertaken to examine the outcomes of photodynamic therapy in solid organ transplant recipients and methods of optimising outcomes in solid organ transplant recipients. Study sizes were small and protocols varied widely, so meta-analysis was not possible; however, photodynamic therapy appears to be an acceptable treatment for approved indications in solid organ transplant recipients in whom ongoing surveillance is maintained to ensure clearance and detect recurrence. Methods for improving efficacy were also reviewed for this population. Improved outcomes may be achieved by combining photodynamic therapy with other local methods such as 5-fluorouracil or ablative fractional laser.

Impact of topical fluorouracil cream on costs of treating keratinocyte carcinoma (nonmelanoma skin cancer) and actinic keratosis.

BACKGROUND: It is unknown whether treatment costs for keratinocyte carcinoma (KC) and actinic keratosis (AK) can be lowered by spending more on chemoprevention. OBJECTIVE: To examine the impact of 1-course treatment with topical fluorouracil (5-FU) on the face and ears on KC and AK treatment costs over 3 years. METHODS: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention trial compared the efficacy of topical 5-FU 5% with that of vehicle control cream for reducing KC risk. Trial data and administrative data on costs and utilization were analyzed to measure postrandomization encounters and treatment costs for KC and AK care. Adjusted models were used to test for statistically significant differences between treatment arms for number of treatment encounters and costs. RESULTS: One year after randomization, the control arm had a higher mean number of treatment encounters for squamous cell carcinoma (0.04) than the intervention arm (0.01) (P < .01). At 1 year, the intervention arm had lower treatment and dermatologic costs: $2106 (standard deviation, $2079) compared with $2444 (standard deviation, $2716) for the control patients (P = .02). After 3 years, the intervention arm incurred a cost of $771 less per patient. LIMITATIONS: Care not provided or paid for by the Department of Veterans Affairs was not included. Results may not be generalizable to other payers. CONCLUSION: We found significant cost savings for patients treated with 5-FU.

MART-1-labeled melanocyte density and distribution in actinic keratosis and squamous cell cancer in situ: Pagetoid melanocytes are a potential source of misdiagnosis as melanoma in situ.

BACKGROUND: Actinic keratosis (AK) and squamous cell carcinoma in-situ (SCCIS) within or near melanoma in situ (MIS) can complicate diagnosis due to overlapping clinical and microscopic features. This study aimed to describe basilar melanocyte density and pagetoid spread in AK and SCCIS for improved diagnostic accuracy. METHODS: A total of 22 AK and 22 SCCIS biopsies containing a margin of uninvolved epidermis were immunostained with MART-1 (melanoma antigen recognized by T-cells 1). The basilar melanocyte:keratinocyte ratio and the number and distribution of pagetoid melanocytes were compared in AK, SCCIS, and uninvolved epidermis. An in-vitro human skin model was created to assess the impact of keratinocyte atypia on melanocyte distribution. RESULTS: The median basilar melanocyte:keratinocyte ratio in SCCIS (1:11.49) was lower than in uninvolved epidermis (1:5.59, P = 0.0011), and the ratio in AK (1:6.94) was similar to uninvolved epidermis (P = 0.987). Pagetoid melanocytes were absent in perilesional skin but common in AK (21/22, P < 0.0001) and SCCIS (22/22, P < 0.0001). Pagetoid melanocytes at or above the mid-spinous layer were more common in SCCIS (21/22) vs AK (7/22, P < 0.0001). Pagetoid melanocytes were present in the in-vitro skin model made with neoplastic but not normal keratinocytes. CONCLUSIONS: Pagetoid melanocytes in AK and SCCIS should be interpreted with caution to avoid overdiagnosis of MIS.

Distinguishing between irritated seborrheic keratosis and squamous cell carcinoma in situ using BCL-2 and IMP3 immunohistochemistry.

BACKGROUND: Distinguishing an irritated seborrheic keratosis (ISK) from a squamous cell carcinoma in situ (SCCIS) can occasionally be challenging, both histologically and clinically. The purpose of this study was to determine if an immunohistochemical profile of select markers can aid in differentiating these two entities. METHODS: We randomly selected and stained 103 ISK and 111 SCCIS for EGFR, IMP3, and BCL-2. IMP3 staining was scored as negative or 0 (0% positive), 1+ (1%-25% positive), 2+ (26%-50% positive), and 3+ (>50% positive). BCL-2 and EGFR were graded as either positive or negative. RESULTS: Sixty five out of 103 (63%) ISKs were positive for BCL-2, none (0%) were positive for IMP3, and 18 (18%) were positive for EGFR. Fifteen out of 111 (14%) SCCISs were positive for BCL-2, 26 (23%) were positive for IMP3, and 27 (24%) were positive for EGFR. BCL-2 was moderately sensitive (63%) and specific (87%) in identifying ISK. IMP3 was specific (100%) but not sensitive (23%) for SCCIS. CONCLUSION: Our findings indicate that the combination of IMP3 and BCL-2 may be of diagnostic utility in distinguishing between ISK and SCCIS in daily clinical practice. EGFR immunohistochemistry did not appear to be useful in this setting.

High-risk human papillomavirus in a child with digital pigmented Bowen's disease: Case report and dermoscopic findings.

Squamous cell carcinoma in situ, also known as Bowen's disease (BD), is a skin malignancy most commonly seen in middle-aged and elderly adults. Pediatric BD is rare and can be a diagnostic challenge for physicians. Digital BD has largely been associated with human papilloma virus. We report an immunocompetent 11-year-old girl with periungual pigmented BD induced by high-risk human papilloma virus.

Cryosurgery + 5% 5-Fluorouracil for Treatment of Superficial Basal Cell Carcinoma and Bowen's Disease [Formula: see text].

BACKGROUND: Superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis) are 2 types of nonmelanoma skin cancers (NMSCs) that are amenable to treatment with topical 5-fluorouracil, cryosurgery, or topical imiquimod, among other destructive and surgical modalities. There are few studies examining the effectiveness of combination therapy with 5% 5-fluorouracil and cryosurgery for the treatment of sBCC and SCCis. OBJECTIVES: Our objective was to study the clinical cure rate achieved with the regimen of cryosurgery and a 3-week course of 5% 5-fluorouracil in the treatment of biopsy-proven sBCC and SCCis. METHODS: A retrospective chart review of patients treated with cryosurgery and a 3-week course of 5% 5-fluorouracil was performed. Immunocompetent patients with biopsy-proven sBCC or SCCis who completed the treatment and attended a follow-up appointment at 6 months were included in the study. RESULTS: On clinical examination, 30 sBCC lesions of the 34 that were assessed and 31 SCCis lesions of the 33 that were assessed demonstrated no evidence of recurrence. The clinical cure rates were found to be 73% (sBCC) and 82% (SCCis), with the inclusion of patients that were lost to follow-up. CONCLUSIONS: This approach may represent a suitable option for select patients for the treatment of SCCis. Further studies with a longer follow-up duration, documentation of histologic cure, and tolerability of this regimen for SCCis are needed. The effectiveness of cryosurgery and 5-fluorouracil for sBCC requires further study.

Clinical efficiency of dynamic observation of patients with epidermal dysplasia of the skin.

OBJECTIVE: Introduction: Non-melanoma skin cancer is the most common type of cancer among the population of Ukraine. The aim: The study of clinical efficacy of dynamic observation of patients with epidermal dysplasia of the skin. PATIENTS AND METHODS: Materials and methods: To study epidermal dysplasia of the skin there was used identifying information of patients, who were under dynamic observation of dermatologists of the State Scientific Institution "Research and Practical Centre of Preventive and Clinical Medicine" of the State Administration in 2013-2017. RESULTS: Results: In 2013-2017, under our supervision there were 245 patients with epidermal dysplasia of the skin, including 66 (27.0%) patients with invasive squamous cell carcinoma, 71 (29.0%) patients with squamous cell carcinoma in situ and 108 (44.0%) patients with actinic keratosis. It has been established that the level of annual progression of epidermal dysplasia of the skin in patients with actinic keratosis was 1.4%, in patients with squamous cell carcinoma in situ and invasive squamous cell carcinoma - 3.22% and 0.86%, respectively. CONCLUSION: Conclusions: It has been found that the level of annual progression of epidermal dysplasia of the skin in patients with a combined course of the above listed pathology of the skin was significantly (p≤0.05) higher and amounted to 8.8%.