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.     

Trisomy 7 in keratoacanthoma and squamous cell carcinoma detected by fluorescence in-situ hybridization

Keratoacanthoma (KA) is generally considered to be a clinically and histologically distinct entity, but it often remains difficult to separate from well-differentiated squamous cell carcinoma (WDSCC). Recently, trisomy 7 has been identified in squamous cell carcinoma of the skin. In this study, we examined classical KA (n=6), WDSCC (n=7) and squamous cell carcinoma with KA-like features (SCC-KA) (n=8) for trisomy 7 by fluorescence in-situ hybridization (FISH) to determine if this chromosomal abnormality is unique to squamous lesions diagnosed as WDSCC, or shared by both KA and SCC. In addition, the pertinent clinical-histopathologic findings were summarized. Trisomy 7 was identified in one KA, one SCC-KA and two WDSCC. This study demonstrates that there is a chromosomal abnormality shared by KA and SCC, providing further evidence that KA is most likely a form of SCC. Further studies are required to determine if trisomy 7 in these lesions is of prognostic significance.     

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.     

Squamous cell carcinoma of the nail apparatus: clinicopathological study of 35 cases

BACKGROUND: Subungual squamous cell carcinoma (SCC) is rare. Its diagnosis is often missed or delayed because the clinical presentation is often atypical and can mimic other conditions such as verruca vulgaris, onychomycosis, trauma-induced nail dystrophy or exostosis. OBJECTIVES: To define the different clinical presentations and the main pathological features and to evaluate the most appropriate surgical management of subungual SCC. METHODS: A retrospective review of all the cases of subungual SCC seen in our institution over a 5-year period. RESULTS: Thirty-five cases were selected. The spectrum of the clinical features encountered was extremely large including leuconychia, subungual hyperkeratosis, trachonychia, subungual tumoral syndrome, longitudinal erythronychia and melanonychia. Most cases (31 of 35) were invasive. Relapse rate after surgical treatment was low after wide surgical excision (5%) of the nail apparatus or amputation of the digit. However, limited surgical excision led to more frequent relapses (56%). CONCLUSIONS: Nail apparatus SCC is often misdiagnosed. Most cases are invasive at the time of diagnosis. Wide surgical excision bears a lower risk of relapse. Micrographic surgery should be considered for a better control in cases treated with limited surgical excision.     

Keratosis lichenoides chronica and eruptive keratoacanthoma-like lesions in a patient with multiple myeloma

We describe a 72-year-old woman with a 13-year history of a lichenoid dermatitis, who developed multiple, papular keratoacanthoma (KA)-like lesions and few crater-like nodules on the extremities over a period of 6 months before our observation. Her medical history also recorded multiple myeloma diagnosed a few years before. The long-standing dermatosis was diagnosed, clinically, as keratosis lichenoides chronica (KLC), although, histologically, a lichenoid tissue reaction pattern was not evident. On the other hand, histology from papular and nodular lesions of recent onset was consistent with a possible early phase of KA and spinocellular carcinoma, respectively. Oral acitretin induced regression of KA-like lesions and improvement of KLC but had no effects on crater-like nodules, which required surgical excision. KLC is a chronic disorder of keratinization characterized by lichenoid hyperkeratotic papules arranged in a linear pattern, erythematosquamous plaques and seborrhoea-like dermatitis. We emphasize in our case the association between KLC and multiple possible KAs, never previously reported, and speculate that these two rare conditions may represent here a 'continuum' from a pathogenetic point of view.     

Treatment of Keratoacanthoma with 5% Imiquimod Cream and Review of the Previous Report

Keratoacanthoma (KA) is a benign epidermal tumor, characterized by rapid and abundant growth, a tendency toward spontaneous regression and histopathologic similarity to squamous cell carcinoma (SCC). Because KA can be easily misdiagnosed as SCC, surgery is considered the treatment of choice. Recently, regression of KAs following application of 5% imiquimod cream (Aldara®) has been reported. We present 4 cases of KA treated with topical imiquimod, applied 3 to 4 times a week. Obvious improvement was observed after 4 to 6 weeks of application and the lesions were almost cleared leaving scars after 9 to 11 weeks. These results show that topical imiquimod can be an effective option for the conservative management of KA as previously reported. We also suggest that lesions treated with imiquimod cream should be considered for biopsy to judge histopathological remission after 5 to 8 weeks of application to shorten the duration of the treatment.     

Proliferating cell nuclear antigen distribution in keratoacanthoma and squamous cell carcinoma

Histologic differentiation of keratoacanthoma (KA) and squamous cell carcinoma (SCC) is often difficult despite well-delineated histopathologic criteria. This has prompted a search for more objective methods to differentiate these two lesions. In the present study, we immunohistochemically examined the distribution of proliferating cell nuclear antigen (PCNA)-positive cells in 11 cases of KA, 7 cutaneous SCC, and 2 atypical squamous proliferations (for which a definitive diagnosis could not be made on routine histology) using a commercially prepared anti-PCNA monoclonal antibody. We found PCNA-positive cells predominantly in the periphery of squamous nests in KA. In contrast, SCC showed a diffuse staining pattern with PCNA-positive cells seen throughout squamous nests. Determining the pattern of PCNA-positive cells is easy, does not require cell counting, and may provide additional histochemical data facilitating the distinction between KA and SCC.     

Rapidly growing squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma (SCC) may present with a history of rapid growth. Although multiple subtypes have been described regarding histologic characteristics and etiology, the subset of rapidly growing squamous cell carcinomas (RGSCC) has not been described. OBJECTIVE: To evaluate and describe the clinical and histologic characteristics of squamous cell carcinomas that grow rapidly. METHODS: Recorded clinical data and biopsies of 26 lesions with a history of rapid growth and histologically diagnosed as SCC were reviewed. RESULTS: Rapidly growing SCC occurred most commonly on the head and neck, followed by hands and extremities, and had an average duration of 7 weeks before diagnosis. The average size of the lesions was 1.29 cm and nearly 20% occurred in immunosuppressed patients. CONCLUSIONS: Some SCCs may grow rapidly. The reason for the rapid growth is not clear and several hypotheses are discussed including immunosuppression and viral etiology. These lesions should be treated aggressively as their behaviour and prognosis are not yet well described.     

Histopathological diagnosis of epithelial crateriform tumors: Keratoacanthoma and other epithelial crateriform tumors

Keratoacanthoma (KA) is a unique and distinct clinicopathological entity, although there is often confusion regarding its differentiation from other types of crateriform tumors. In this study, the clinicopathological features of 380 epidermal crateriform tumors with a central keratin plug were re‐examined and the tumors were histologically classified into seven types: (i) crateriform verruca; (ii) crateriform seborrheic keratosis; (iii) KA; (iv) KA with a conventional squamous cell carcinoma (SCC) component (KA‐like SCC and KA with malignant transformation); (v) crateriform Bowen's disease; (vi) crateriform SCC arising from solar keratosis; and (vii) crater form of infundibular SCC. Our study proved that incidence of SCC developing in KA lesions was 17.4%. The incidence rate differed depending on a patient's ages: 8.3% in patients less than 70 years of age and 24.3% in those aged 70 years and older. Nearly all of the malignant crateriform neoplasms (94.7%) occurred on sun‐exposed areas. Lesions on the face included 138 KA (59.5%), 65 malignant crateriform neoplasms (28%) and 29 benign crateriform neoplasms (12.5%). We conclude that KA is not a variant of SCC, but a benign and frequently regressing proliferative lesion or borderline neoplasm, although there is the potential for SCC to arise within KA. Because the incidence of SCC developed in KA lesions and the incidence of other malignant crateriform neoplasms are higher in patients aged 70 years and older, KA‐like lesions on sun‐exposed areas over 70 should be assessed carefully in consideration of the potential risk of malignancy.     

Differentiating squamous cell carcinoma from keratoacanthoma using histopathological criteria. Is it possible? A study of 296 cases

BACKGROUND: Squamous cell carcinoma (SCC) and keratoacanthoma (KA) are sometimes difficult to distinguish by histopathological examination, since cytological features are similar in both tumors. Distinctive criteria - mainly architectural - have therefore been proposed as an aid in diagnosis. OBJECTIVE: The purpose of this study was to evaluate the reliability of some of the criteria used to make a distinction between SCC and KA. METHODS: 296 fully excised tumors previously classified as SCC or KA were randomized and examined independently by two examiners. Fourteen criteria, mainly based on the architecture of the tumors, were determined on the 262 slides for which a consensual diagnosis was made. RESULTS: No single criterion was sufficiently sensitive and specific to allow a clear-cut differential diagnosis. The 5 most relevant criteria were epithelial lip, sharp outline between tumor and stroma in favor of KA and ulceration, numerous mitoses and marked pleomorphism/ anaplasia in favor of SCC. Intraepithelial polymorphonuclear abscesses, intraepithelial elastic fibers, parakeratosis and dyskeratosis and extension more lateral than downward were not distinctive criteria, although they are considered as classic distinctive features. CONCLUSION: Many of the criteria commonly used for the differential diagnosis of SCC and KA are not reliable. The combination of the 5 most useful criteria does not significantly increase the specificity or sensitivity of the histological diagnosis in difficult cases. Atypical or difficult cases should therefore be considered and treated as SCC, since a clear-cut distinction is not possible even with the aid of the most relevant criteria.     

Kutanes Plattenepithelkarzinom

Squamous cell carcinoma (SCC) of the skin accounts for 20?% of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects. Radiotherapy can be discussed as an alternative to surgery for inoperable tumors or as adjuvant therapy for a high risk of recurrence. In SCC with distant metastases various chemotherapeutic agents are used; however, there is no standard regimen. The epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint blockers can be discussed as treatment options, preferentially in clinical trials. There is no standard follow-up schedule for patients with SCC. A risk-adapted follow-up is recommended based on the risk of metastatic spread or development of new lesions primarily by dermatological control and supplemented by ultrasound investigations in high risk patients.     

Large atypical melanocytic nevi in recessive dystrophic epidermolysis bullosa: clinicopathological, ultrastructural, and dermoscopic study

A 3-year-old boy with recessive dystrophic epidermolysis bullosa developed a rapidly growing, large, acquired irregular melanocytic nevus on the lower aspect of the back. The lesion was clinically atypical and fulfilled the criteria for a malignant melanocytic proliferation. A complete surgical excision was performed. Histopathologic examination disclosed a compound melanocytic nevus without melanocytic atypia. Ultrastructural examination showed melanocytic cells located both at the roof and the floor of the blister. Several months later, three pigmentary lesions with a similar clinical appearance developed. Periodic clinical and dermoscopic examinations were recommended. Dermoscopic examination disclosed a globular pattern with brown globules and black dots distributed all over the lesions. The lesions also exhibited blue-greyish dots and multiple rounded white structures corresponding to milia-like cysts. No dermoscopic features suggestive of malignancy were noted. Acquired melanocytic nevi showing atypical clinical features have been reported to occur in areas of blistering in patients with epidermolysis bullosa. These nevi appear as large, asymmetrical pigmentary lesions with irregular borders. Initially, they are very dark in pigmentation, with color variegation and loss of pigment, and even becoming papillomatous over time. Histopathologic examination can show features of compound/junctional nevus as well as persistent/recurrent nevus. The concept of "epidermolysis bullosa nevus" has been proposed to define these peculiar lesions. The clinical, histopathologic and ultrastructural features of these nevi are reviewed. The usefulness of dermoscopic examination in the routine diagnosis and follow-up of these lesions are stressed.     

Histopathologic features of multiple cutaneous squamous cell carcinomas of the lower extremity

Recent studies suggest cutaneous squamous cell carcinomas (SCCs) of the leg, particularly those occurring multiply in sun exposed skin of nonimmunosuppressed women, are a distinct clinical subtype. There are few reports of the histopathologic features of this subtype. A retrospective chart review of 4 patients with multiple SCCs on the leg was performed and a total of 35 biopsies from the legs examined. Histopathologically, the tumors lacked adjacent actinic keratosis (AK) and often had adjacent basaloid retiform proliferations. Most lesions (all but one) were well differentiated and about 40% could be classified histopathologically as keratoacanthoma. Perineural invasion was absent in all but one case. Using the American Joint Committee on Cancer (AJCC) staging criteria for SCC, 21 tumors were Stage I, and 9 Stage II. During 7–10 years of follow‐up, no recurrence or metastasis occurred. Patients with multiple SCCs on the lower extremities can have a range of histopathologic features, from keratoacanthoma‐like to well‐differentiated SCC.     

Quantitation of S100 protein-positive cells in inflamed and non-inflamed keratoacanthoma and squamous cell carcinoma

Langerhans cells (LC) were identified and quantitated in non-inflamed keratoacanthoma (KA), inflamed KA, non-inflamed squamous cell carcinoma (SCC), and inflamed SCC, by their content of S100 protein. The number of LCs per high-power field was markedly increased in inflamed KA when compared to the other groups. Using similar methods on frozen sections, the expression of HLA-DR was identified on keratinocytes in KA in areas of inflammation but not in other lesions under study. We hypothesize that increased numbers of LCs in inflamed KA are part of the process which results in tumor regression.     

DNA image cytometry of keratoacanthoma and squamous cell carcinoma

The distinction between the keratoacanthoma (KA) and the squamous cell carcinoma (SCC) can sometimes be difficult on the basis of histologic and clinical criteria. The possible diagnostic significance of DNA ploidy initiated the present study evaluating the DNA ploidy in paraffin-embedded tissue sections of 7 KA and 15 SCC, and fresh frozen tissue touch preparations of 15 of the same cases using the CAS 200 Image Analyzer. In paraffin-embedded tissue sections the main peak DNA index was based on normal epidermis, and ranged from 1.03 to 1.59 in KA and from 1.47-2.71 in SCC. The DNA Index (DI) discriminated KA from SCC in 17 of 22 cases (p less than 0.0007). The highest DNA content of single nuclei ranged from 9.0-18.0 picograms (pg) (DI 2.9-6.03) in KA and 14.8-38.6 pg (DI 4.0-11.03) in SCC. The highest DNA content discriminated KA from SCC in 16 of 22 cases (p less than 0.003). In fresh frozen tissue touch preparations from 15 of the same lesions, there was considerable overlap in DNA indices of KA (0.534-1.39) and SCC (0.464-1.41). Abnormal DNA peaks seen in histograms from three SCC in paraffin-embedded tissue sections were lost in the touch preparation histograms, probably due to inadequate sampling. Therefore, image analysis of paraffin-embedded tissue sections is better able to distinguish KA from SCC than touch preparations.     

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。     

Perforating elastic fibers (‘elastic fiber trapping’) in the differentiation of keratoacanthoma,conventional squamous cell carcinoma and pseudocarcinomatous epithelial hyperplasia

Keratoacanthoma (KA), an epithelial neoplasm occurring in sun‐exposed skin of the elderly, is considered a well‐differentiated form of conventional squamous cell carcinoma (SCC) that often follows a course of spontaneous regression. Distinguishing KA from conventional SCC or pseudocarcinomatous epithelial hyperplasia ensures proper diagnosis, treatment and management. For some time, perforating elastic fibers have been utilized in differentiating KA from SCC. This phenomenon may also occur in association with scars and hypertrophic lupus erythematosus (LE). To assess the diagnostic utility of perforating elastic fibers, we compared their incidence in KA, SCC, scars with overlying pseudocarcinomatous hyperplasia, hypertrophic LE, hypertrophic lichen planus (LP) and lichen simplex chronicus (LSC). A retrospective case search identified 359 lesions and the presence of perforating elastic fibers was evaluated using routinely stained sections. This phenomenon was documented in all studied groups except hypertrophic LP. The incidence was found to be 71% in KA, 37% in SCC, and was lowest in inflammatory conditions with associated pseudocarcinomatous hyperplasia (hypertrophic LP 0%, hypertrophic LE 5.9% and LSC 28.2%). The observed frequency in pseudocarcinomatous hyperplasia overlying scars (57.8%) vs. KA (71%) was not statistically different. Although elastic fiber trapping has potential value as a diagnostic criterion for KA, dermatopathologists should consider its limitations. Its diagnostic utility was greatest in distinguishing KA from hypertrophic LE and hypertrophic LP. Conversely, elastic trapping is not helpful differentiating pseudocarcinomatous hyperplasia from recurrent/persistent KA following surgery.     

Eruptive squamous cell carcinomas, keratoacanthoma type, arising in a multicolor tattoo

Permanent tattoos are formed through the injection of ink solids through the epidermis into the dermis and can cause multiple adverse reactions. We report a 38-year-old man who presented to our Dermatologic Surgery Unit with a diagnosis of a superficially invasive squamous cell carcinoma (SCC), keratoacanthoma (KA) type, of the left forearm in a 1-month-old tattoo. Since his initial biopsy, he developed four more similar lesions on his left forearm within his tattoo. On physical examination, the patient had a large, multicolor tattoo on his left forearm, a well-healed surgical biopsy site and four erythematous hyperkeratotic papules within differently pigmented areas of the patient's tattoo. Histopathological examination showed KA and tattoo pigment. Based on the eruptive nature of these lesions, their clinical presentation and the histopathological changes, we report this as the first case of eruptive KA arising in a multicolor tattoo.     

Squamous cell carcinoma of the skin: epidemiology,classification, management,and novel trends

Squamous cell carcinoma (SCC) is the second most common non‐melanoma skin cancer. It originates from epidermal keratinocytes or adnexal structures (such as eccrine glands or pilosebaceous units). We describe the salient features of cutaneous SCC. We also review novel classification schemes proposed during the last decade which attempt to stratify SCC lesions based on prognosis. Biopsy leads to definitive diagnosis. Treatment includes surgical excision; Mohs micrographic surgery produces excellent cure rates and spares the maximal amount of tissue. Other modalities include electrodessication and curettage, cryosurgery, radiotherapy, topical medications, photodynamic therapy, and systemic therapy. Management and follow‐up depend on the risk stratification of individual lesions.     

Chronic cutaneous graft-versus-host disease simulating hypertrophic lupus erythematosus--a case report of a new morphologic variant of graft-versus-host disease

The spectrum of clinical and histopathologic features associated with chronic graft-versus-host disease (GVHD) is broad, with recognized variants simulating scleroderma, lichen sclerosus, eosinophilic fasciitis, and de novo diffuse melanoderma. We report a case of a patient with multiple myeloma who presented approximately 1 year after his allogeneic hematopoietic stem cell transplantation with lesions of chronic lichenoid GVHD that harbored features of hypertrophic lupus erythematosus (LE) and that was initially mistaken for a superficial well-differentiated squamous cell carcinoma (SCC). However, in 4 years of follow-up, the patient failed to develop any evidence of cutaneous or systemic LE, actinic damage, or SCC, and the lesions cleared with topical and systemic treatments appropriate for chronic GVHD. For proper interpretation of the histologic findings of GVHD, it is important for the dermatopathologist to be aware of unusual manifestations. Knowledge of the occurrence of hypertrophic LE and familiarity with its histologic features is also important to avoid an erroneous diagnosis of SCC in immunosuppressed patients.