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REVIEW ARTICLE Table of Contents  
Ahead of print publication
Polypoid basal cell carcinoma: A scoping review


1 Department of Dermatology, Chang-Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
2 Department of Dermatology, Taipei Veterans General Hospital; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3 Department of Dermatology, Taipei Veterans General Hospital; School of Medicine, National Taiwan University, Taipei, Taiwan
4 Department of Dermatology, Taipei Veterans General Hospital; Faculty of Medicine, School of Medicine; Department of Dermatology; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

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Date of Submission13-Apr-2022
Date of Decision28-May-2022
Date of Acceptance05-Jun-2022
Date of Web Publication23-Aug-2022
 

  Abstract 


Polypoid basal cell carcinoma (BCC) is characterized by a stalk connecting the tumor and skin surfaces, with neoplastic cells restricted in the polypoid zone microscopically. A thorough review of polypoid BCC is still lacking. Thus, we performed this scoping review to investigate the clinical manifestations, dermoscopic features, histopathology, treatment, and prognosis of polypoid BCC. A literature search was conducted in the PubMed, Embase, Web of Science, and Cochrane databases until December 23, 2021. Studies reporting at least one patient with polypoid BCC following the pathology and clinical criteria were included. A total of 47 studies with 54 patients with solitary polypoid BCC and 13 patients with multiple polypoid BCCs were included. Solitary polypoid BCC occurred at a relatively younger age, with an equal sex ratio. These tumors most commonly presented as red or flesh-colored pedunculated papules and were commonly distributed over nonsun-exposed areas. Most tumors were managed with excision, and recurrence or metastasis was seldom reported. Most patients with multiple polypoid BCCs had basal cell nevus syndrome and presented with generalized distributed, flesh-colored, or brown papules mimicking skin tags. Typical dermoscopic features of BCC could still be observed in these lesions, including arborizing vessels, blue-gray globules, and ovoid nests, which could aid in early diagnosis. In conclusion, polypoid BCC is a distinct variant of BCC with pedunculated morphology. Physicians should be aware of polypoid BCC and may use dermoscopy to aid in early diagnosis and treatment.

Keywords: Basal cell carcinoma, basal cell nevus syndrome, polypoid, scoping review


How to cite this URL:
Wu PC, Dai YX, Chou YJ, Chang YT, Chen CC, Ma SH. Polypoid basal cell carcinoma: A scoping review. Dermatol Sin [Epub ahead of print] [cited 2022 Sep 29]. Available from: https://www.dermsinica.org/preprintarticle.asp?id=354330





  Introduction Top


Basal cell carcinoma (BCC), the most prevalent skin malignancy worldwide, is believed to originate from keratinocytes of the stratum basale or hair follicle.[1],[2] The pathogenesis of BCC is driven by both genetic and environmental factors, including ultraviolet B exposure, chronic arsenic exposure, and mutations in PTCH1, SMO, or SUFU, which are collectively included in the sonic hedgehog pathway.[3],[4],[5] Although they rarely metastasize, the tumor cells of BCC may infiltrate surrounding tissue, leading to local tissue destruction and recurrence if not completely excised.[5] BCC is rarely associated with a fatal outcome; however, the economic burden is substantial and rising due to its high incidence, with an average annual cost of 8.1 billion between 2007 and 2011 in the US.[6]

The clinical manifestations of BCC are variable, with nodular, pigmented, superficial, and morpheaform BCC being the most commonly reported morphology.[5] Polypoid BCC, also called acrochordon-like BCC, is a distinct form of BCC first defined by Megahed in 1999.[7] In general, polypoid BCC is characterized by a stalk connecting the tumor part and the skin surface, and the neoplastic cells are restricted in the polypoid zone microscopically.[8] Although polypoid BCC shares morphological similarities with fibroepithelioma of Pinkus (FeP) clinically, it lacks the histopathological features of FeP, such as anastomosing strands of basaloid cells arranged in a fenestrated pattern with surrounding fibrous stroma.[5],[9] Several reports of polypoid BCC have been published in recent years; however, a thorough review of all the evidence remains lacking. Thus, we performed this scoping review to investigate the clinical manifestations, dermoscopic features, histopathology, treatment, and prognosis of polypoid BCC.


  Materials and Methods Top


This meta-analysis was registered in PROSPERO (CRD42021293529) and performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews.[10] The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant studies from their respective inception to December 23, 2021. The relevant terms, including “polypoid,” “acrochondron,” “BCC,” and “basal cell nevus syndrome,” were used and conducted with free text, medical subject headings (MeSH in PubMed and Emtree in Embase), and abbreviations in the literature search. Keywords were combined using appropriate Boolean operators, and a primary search strategy was developed without limitations regarding language or published data [Table S1]. In addition, the reference lists of all the searched articles were examined.

We included studies reporting at least one patient who had developed polypoid BCC following the pathology and clinical criteria revised from the definition by Megahed et al.[7] In the pathology criteria, tumor nests should be restricted to the polypoid part of the tumor without infiltrating into the underlying dermis. If the case report did not provide enough low-power field view details or did not describe the pathological findings of the tumor cells, we then judged the tumor based on the clinical criteria. The clinical criteria were matched if the tumor had a clinically apparent stalk that connected the tumor part and underlying skin. Review articles and reports of patients diagnosed with FeP or BCC arising in a skin tag were excluded. Two experienced reviewers (Wu and Ma) independently performed the literature search, data extraction, and quality assessment using the Joanna Briggs Institute (JBI) critical appraisal tool for case reports and series [Table S2].[11],[12],[13],[14]

The following data were extracted independently by two reviewers (Wu and Ma) from the included studies: first author, year of publication, patients' demographic information (sex and age), clinical features of the polypoid BCC (size, location, and pathology), treatment, and prognosis. We further classified the included patients into two groups: solitary polypoid BCC and multiple polypoid BCCs associated with genetic disorders or other systemic diseases. Any discrepancies between the two reviewers were resolved by a third reviewer (Dai).


  Results Top


As shown in [Figure 1], 2743 studies were identified in the four major databases and manual searches. We excluded 964 studies due to duplication and 1712 unrelated studies after assessing the title or abstract. A total of 67 studies were reviewed, with 47 studies meeting the inclusion criteria for qualitative synthesis. A total of 54 patients with solitary polypoid BCC and 13 patients with multiple polypoid BCCs were included in this study [Table 1]. Most studies exhibited 6 out of 8 points in all questions designed by JBI critical appraisal tool.
Figure 1: PRISMA flowchart of the selection of studies. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

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Table 1: Characteristics of polypoid basal cell carcinoma

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Patient characteristics

Detailed information on the included patients is presented in [Table 1] and [Table 2]. The mean age of the included patients with solitary and multiple polypoid BCCs was 62.7 years and 18.0 years, respectively. The numbers of males and females were similar in patients with solitary polypoid BCC, but a slight female predominance was found in patients with multiple polypoid BCCs. Most cases with solitary polypoid BCC have been reported in Asian countries, especially Japan and Korea. As in the multiple group, most of the reported patients were from America.
Table 2: Summary of characteristics of solitary and multiple polypoid basal cell carcinomas

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Clinical manifestations of polypoid BCCs

The clinical image of polypoid BCC is shown in [Figure 2]. The mean size of the polypoid BCCs of all included patients was 2.54 cm, with 2.90 cm in the solitary group and 1.07 cm in the multiple group. In the solitary group, the most commonly reported colors were red (25.9%), flesh-colored (18.5%), brown (13.0%), and black (13.0%), while in the multiple group, the most frequently reported color was fleshed-colored (53.8%) and brown (23.1%). Regarding the location of the tumor, the head and neck (35.2%) was the most common site in the solitary group, followed by the extremities (22.2%) and the inguinal area (22.0%). Some of the tumors in the solitary group also developed on preexisting dermatosis, including nevus sebaceous and nevus lipomatosus superficialis.[7],[15] Twelve out of 13 cases (92%) with multiple polypoid BCCs had basal cell nevus syndrome (BCNS),[16],[17],[18],[19] and the remaining one was related to radiotherapy for treatment of lymphoma in childhood.[20]
Figure 2: Clinical image of polypoid basal cell carcinoma.

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Dermoscopic features of polypoid basal cell carcinoma

The dermoscopic features of polypoid BCCs were only reported in four studies (two in the multiple group and two in the solitary group).[18],[20],[21],[22] The reported dermoscopic features were similar in these studies, including arborizing vessels, blue-gray globules, and ovoid nests.

Pathology features of polypoid basal cell carcinoma

The pathology of polypoid BCC is shown in [Figure 3]. Nodular-type BCC is the most commonly reported subtype (64.8% in the solitary group and 46.2% in the multiple group). Focal adenoid features, cystic space, and hyperpigmentation were also common. Some rare histological variants have also been reported, including the keratotic and infundibulocystic types. Infundibulocystic and follicular types are more likely to be reported in patients with BCNS.
Figure 3: Histopathology of polypoid basal cell carcinoma. Note the infiltrative basaloid tumor cells with peripheral palisading, retraction artifact, pigmentation, and focal keratinization restricted in the polypoid zone.

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Treatment and prognosis of polypoid basal cell carcinomas

Most tumors were excised. The margin of excision was reported in 16 cases, ranging from 1 mm to 30 mm (mean, 9.34 mm) in the solitary group. In the multiple group, 6 (46.2%) cases were treated with excision, and 3 (23.1%) cases were treated with laser surgery. Recurrence was not reported in the literature, but lung metastasis and subsequent mortality were reported in one case with giant solitary polypoid BCC.[23]


  Discussion Top


In this study, we reviewed all available literature regarding polypoid BCC, and 54 patients with solitary polypoid BCC and 13 patients with multiple polypoid BCCs were outlined and characterized. A literature search without language restriction, inclusion and analysis of cases with multiple polypoid BCCs, and a focus on the dermoscopic and pathological features were the major strengths of our study.

Polypoid BCC was a seldom-described clinical variant of BCC, which was first defined by Megahed in 1999.[7] This rare type of BCC had a distinctive pedunculated morphology with neoplastic cells aggregated in the polypoid part. Regarding the demographic characteristics, polypoid BCC occurred in a relatively younger age (mean age, 62.72 years) with an equal sex ratio compared to other types of BCC. The median age of diagnosis for all BCCs ranged from 64.5 to 75 years, and a male predominance is shown in most literature (1.08 to 2:1).[5],[24],[25],[26],[27],[28],[29],[30],[31],[32] However, some studies have suggested an equal or female predominance of BCCs, especially in the younger population and truncal lesions, which may be linked to the exposure of the tanning bed at a younger age.[33],[34] However, such an explanation seems less plausible for polypoid BCCs, as most cases were reported in Asia, where tanning bed use was far less popular than in Western countries.

Polypoid BCC is characterized by its pedunculated morphology, with red or flesh color plus variable pigmentation being the most common colors in the solitary group (25.9% and 18.5%, respectively). These lesions were most frequently found in the head-and-neck region (35.2%), extremities (22.2%), and inguinal areas (22.2%), with a higher distribution in nonsun-exposed areas. The distribution pattern was quite different from nodular BCCs, the most common subtype, which is located mostly over the head-and-neck region (57.5%–89.6%).[25],[32],[35],[36],[37] The mean of the largest diameter of solitary polypoid BCCs was 2.90 cm, which was also larger than that of nodular BCCs (0.92–1.21 cm) in previous series.[27],[32],[37],[38] The larger size of polypoid BCCs may be partly related to its resemblance of other benign lesions, such as pedunculated nevus, neurofibroma, and soft fibroma, resulting in negligence and diagnostic delay.[37] The average duration for polypoid BCCs was 7.35 years, which was far longer than that of other BCCs (1.5–2.1 years).[30],[39],[40],[41]

Several tools may aid in early diagnosis, and dermoscopy is a useful and noninvasive choice. The dermoscopic features of polypoid BCCs were described in recent case reports, which showed much similarity to nodular BCCs, including blue-gray globules, ovoid nests, and arborizing vessels.[21],[42],[43],[44] In contrast, FeP, one of the major differential diagnoses of polypoid BCC, owned characteristic dermoscopic features. The presence of fine arborizing vessels and gray-blue dots was observed in both polypoid BCCs and FeP, but unique type of white streaks and leaf-like patterns, white spoke-wheel areas, negative network, and follicular keratotic plugs were distinctive presentations of FeP.[45],[46],[47],[48] According to Zalaudek et al., dermoscopy could reach a 90% correct diagnosis of FeP based on these characteristic features.[46] Reflectance confocal microscopy had been used in one report by Yildiz et al. to aid in the diagnosis of polypoid BCC, which showed epidermal polarization, tumor islands with variable sizes, and canalicular vessels.[20] The pathological features of polypoid BCCs were also analyzed, and most cases could be categorized into nodular type with variable pigmentation, ulceration, and focal cystic or adenoid component.

The mechanisms of solitary polypoid BCCs have been proposed in some case reports. Ultraviolet B-driven mutagenesis and subsequent activation of the hedgehog pathway in keratinocytes may result in the development of BCC.[5] However, such a mechanism seems less plausible in polypoid BCCs, as more than half of these cases are distributed in nonexposed areas. In addition, most cases have been reported in Asia, especially Japan and Korea, and certain genetic backgrounds may result in ethnic differences. Further genetic analysis may be needed to elucidate the mutagenesis of polypoid BCCs. Some studies have discussed the mechanisms behind pedunculated structures. Sakai et al. hypothesized that tumor growth pattern (initial rapid growing and subsequent slow growing), friction and environmental factors, as well as the weight of the tumor mass may contribute to the characteristic pedunculation.[49]

Multiple polypoid BCCs are mainly found in patients with BCNS. These patients were generally younger (mean age, 18.00 years), female (61.5%), and had smaller lesions (mean, 1.07 cm) than solitary polypoid BCCs. Most of the skin lesions were flesh-colored or brown, with a generalized distribution. These lesions may mimic skin tags clinically, but the dermoscopic examination may reveal blue-gray globules, ovoid nests, and arborizing vessels, which were not shown in skin tags.[18] BCNS, also known as Gorlin-Goltz syndrome, is an autosomal-dominant disease caused by mutations in PTCH gene, a tumor suppressor gene.[18] Most patients with BCNS suffered from multiple BCCs, odontogenic cysts, pitting dimples at palmar and plantar sites, and skeletal anomalies in their early childhood.[19] Sun-exposed areas of the body, such as head, neck, and forearms, were substantially augmented susceptibility to multiple BCCs in BCNS cases.[50] As multiple polypoid BCCs may be the presenting symptoms of BCNS, children presenting with numerous acrochordon-like growths should receive prompt evaluation. In our study, only one case of multiple polypoid BCCs was not associated with BCNS but was related to childhood radiotherapy for treatment of lymphoma.[20] Radiation exposure has been proved to enhance the risk of BCCs in previous studies, mainly due to gene mutations, chromosome aberrations, generation of reactive oxygen species, and carcinogenesis effects.[50],[51] The radiation exposure history and the absence of other typical features of BCNS could differentiate BCNS-associated and non-BCNS-associated multiple polypoid BCCs.

Surgical excision is the main treatment of choice for solitary polypoid BCC, with a surgical margin ranging from 1 mm to 30 mm and a mean margin of 9.34 mm. Although the average diameter of the lesion was larger, the prognosis of polypoid BCCs seemed to be relatively fair, with only one patient reporting lung metastasis and subsequent death due to disease progression. Overall, the risk of metastasis and death in larger polypoid BCC (≥2 cm) was 4.76% (1 in 21 cases), which was lower than other types of BCC (6.5%) according to one study by Morgan et al.[52] Treatment for multiple polypoid BCCs included surgical excision and laser therapy. No local recurrence or metastasis was reported in these cases; however, the follow-up periods were inconsistent among the included studies.

There were some limitations to this study. First, although we tried to include all the available literature, some case reports were still unable to obtain, especially those published in Japan before 2000. In one case report by Yashiro et al.,[53] 63 reported cases of polypoid BCC in Japan between 1985 and 2014 showed a male predominance (1.52:1), older age (mean age, 67.4 years), longer duration (7.3 years), and slightly larger lesion size (2.79 cm). In addition, 43% of the lesions were found in the head-and-neck region, 32% in the trunk, and 14% in the inguinal area. Although there were some numerical differences compared to our current study, the overall characteristics and trends were similar when compared to other types of BCC. Second, another potential source of bias is the definition of polypoid BCC. Most of the reported cases were categorized as polypoid BCC based on the pedunculated morphology with neoplastic cells aggregated in the polypoid part. However, some reported “polypoid BCCs” did not fulfill the above criteria and were excluded from our analysis. To standardize the inclusion criteria, each case was examined thoroughly based on the above definition by the two reviewers. A clear criterion for polypoid BCC diagnosis may be needed in future. Third, due to the paucity of polypoid BCC, most of the studies were case reports or case series with rather short follow-up periods. Studies with a greater number of patients with longer follow-up periods are warranted to obtain more information on this unique variant of BCC.


  Conclusion Top


Polypoid BCC is a distinct variant of BCC with a pedunculated morphology. Physicians should be aware of this variant of BCC and may use dermoscopy to aid in early diagnosis and treatment.

Role of the Funder/Sponsor

The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Contribution statement

The manuscript has been read and approved by all the authors, and every author believes that this manuscript represents honest work.

Financial support and sponsorship

This study was funded by the Ministry of Science and Technology (MOST), ROC, under the grant MOST 110-2314-B-075-056-MY3.

Conflicts of interest

Prof. Yun-Ting Chang and Prof. Chih-Chiang Chen, editorial board members at Dermatologica Sinica, had no roles in the peer review process of or decision to publish this article. The other authors decalared no conflicts of interest in writing this paper.


  Supplementary Material Top








The Joanna Briggs Institue (JBI) critical appraisal tool for case report and series

QY: Were patient's demographic characteristics clearly described?

Q2: Was the patient's history clearly described and presented as a timeline?

Q3: Was the current clinical condition of the patient on presentation clearly described?

Q4: Were diagnostic tests or assessment methods and the results clearly described?

Q5: Was the intervention(s) or treatment procedure(s) clearly described?

Q6: Was the post-intervention clinical condition clearly described?

Q7: Were adverse events (harms) or unanticipated events identified and described?

Q8: Does the case report provide takeaway lessons?



 
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Correspondence Address:
Chih-Chiang Chen,
Department of Dermatology, Taipei Veterans General Hospital, Taipei
Taiwan
Sheng-Hsiang Ma,
Department of Dermatology, Taipei Veterans General Hospital, Taipei City
Taiwan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1027-8117.354330



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