|Year : 2015 | Volume
| Issue : 1 | Page : 24-28
Cutaneous basal cell carcinoma: A morphological spectrum
Prema Saldanha, PR Shanthala, Krishnaraj Upadhaya
Department of Pathology, Yenepoya Medical College, Mangalore, Karnataka, India
|Date of Web Publication||13-Apr-2015|
Prof. Dr. Prema Saldanha
Department of Pathology, Yenepoya Medical College, Mangalore - 575 001, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Basal cell carcinomas (BCCs) are much less common than squamous cell carcinomas (SCCs) among the cutaneous malignancies in India. Most of the BCCs behave indolently with low metastatic potential. Histological diagnosis and classification of BCCs are essential to predict their behavior and course. This study was done to analyze the histological spectrum. Materials and Methods: A retrospective study was done with 25 cases diagnosed over a 5-year period. The relevant clinical details were obtained and the slides were reviewed. Results: Twenty-five cases of cutaneous BCC were analyzed. The age of the patients ranged from 50 to 95 years with equal incidence in males and females. The duration of the lesions varied from 2 months to 10 years. Most of the lesions occurred on the face with 12 cases in the periorbital region and 9 cases on the cheek. There were one case each with a lesion on the scalp, back, chest, and abdominal wall. The histological subtypes found in our study included nodular type (undifferentiated -14 cases, and with differentiation -7 cases), nodulocystic type -1 case and basosquamous (metatypical) type -3 cases. Conclusion: It is important to differentiate basal cell carcinoma from other skin tumors and also type the tumors as the prognosis and risk of recurrence depends on the subtype.
Keywords: Basal cell carcinoma, metatypical carcinoma, skin
|How to cite this article:|
Saldanha P, Shanthala P R, Upadhaya K. Cutaneous basal cell carcinoma: A morphological spectrum. Arch Med Health Sci 2015;3:24-8
| Introduction|| |
Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of skin are the most frequent malignant conditions of the skin worldwide. BCCs are the commonest cutaneous tumors in Western literature accounting for approximately 70% of all malignant diseases of the skin. The exact incidence in India is not known. In dark-skinned individuals, SCC is found to be commoner than BCC. Various studies from India consistently report SCC to be the most prevalent skin malignancy. In dark-skinned people, SCC often occurs in sites that have not been exposed to the sun and is often aggressive. The incidence of BCC appears to be increasing worldwide. 
Histological diagnosis and classification of BCCs are essential in view of planning patient management. The different morphological types of BCCs are associated with low risk or high risk behavior and are factors of prognostic significance. Other factors of importance include size of the lesion and the status of excised surgical margins.  There is no unified and generally accepted classification of BCCs. When classifying BCCs, the growth pattern is important since it gives more information about bio-behavior and the differentiation of the tumors is of less importance. 
| Materials and Methods|| |
In this study, a review was made of the histopathology cases from July 2009 to June 2013 received from the Medical College Hospital and private hospitals in and around Mangalore. The clinical details from the records were noted. The histology was studied using the routine Haematoxylin and Eosin (H&E) stain. The tumors were classified according to the World Health Organization (WHO) classification.  Cell morphology, differentiation, stromal changes, and histological prognostic factors were noted.
| Results|| |
There were 25 cases of cutaneous BCC during this period. The age of the patients ranged from 50 to 95 years with equal incidence in males and females. The duration of the lesions varied from 2 months to 10 years. There was one case of recurrent tumor presenting within a year. The case of basoquamous carcinoma occurred on the anterior abdominal wall over a chicken-pox scar in a 78-year-old woman. One of the cases in a 65-year-old man was clinically mistaken for spectacle rash. This patient also had xanthelasma of the eyelids.
Periorbital (upper and lower eyelids and medial canthus) lesions were the most common comprising of 12 cases. There were nine lesions on the cheek, and one each on the scalp, back, chest, and abdominal wall. The lesions were clinically diagnosed as BCC in only three cases and as a malignant tumor (SCC, melanoma) in two other cases. The other clinical diagnoses were seborrheic keratosis, naevi, and spectacle rash. There was one case with multiple ulcers. The size of the lesions ranged from 0.4 to 4 cms. The various histological types are shown in [Table 1].
|Table 1: The details of the cases of basal cell carcinoma (BCC) found in our study|
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Ulceration was seen in five cases, melanin pigment in 16 cases, and cystic change in 12 cases. One case had abundant melanin pigment and was diagnosed as pigmented type. The various stromal reactions encountered in our study were mononuclear inflammatory reaction in 14 cases, an inflammatory infiltrate with eosinophils in 5 cases, foreign body granulomatous reaction in 5 cases, fibrosis in 7 cases, mucinous/myxoid change in 4 cases, and amyloid in 2 cases. Peritumoral lacunae (retraction artefact) were seen in 18 cases. In one case the tumor was seen focally infiltrating the subcutaneous fat and one case showed perineural invasion. In one case, the excision was not complete.
| Discussion|| |
Most studies report that in the Indian context BCCs are relatively uncommon which is also reflected in our series. BCCs are found to occur in older people. They have also been documented in children and young adults. They are more common in males, probably due to greater occupational and recreational exposure to ultraviolet light.  An Indian series reported an unusual female preponderance.  The patients in our study were all over the age of 50 years with equal gender incidence.
BCCs are found predominantly on areas of skin exposed to the sun. They are rarer in dark-skinned individuals.  Most (85%) of the lesions are found on the head and neck, whereas approximately 15% develop on the shoulders, back, or chest.  In the present study, most of the cases were observed on the face and eyelid. BCC is the most common malignant tumor involving the lower eyelid, and as at other sites exposure to sunlight is an important risk factor. , There are isolated reports documenting involvement of the BCC at uncommon sites like in the lower extremities, clitoris vulva, and the perianal region. 
BCC is thought to be derived from basaloid epithelia located in the follicular bulges, in the anagen hair bulbs, and the follicular matrix cells, and in specific basaloid cells of the interfollicular epidermis. The cells of origin are believed to be pluripotent progenitor epithelial cells in adults. 
Epidemiologic data and experimental evidence indicate that ultraviolet B (UVB) radiation (wavelength 290-320 nm) includes the most important wavelengths for the induction of skin cancer. Depletion of ozone in the atmosphere increases the levels of UVB radiation at the surface of the earth and the risk of skin cancer. An increase of 2-4% in the incidence of tumors for each 1% reduction in the ozone layer has been suggested. , Other important etiological agents include radiation, and exposure to arsenic, coal tar, and other hydrocarbons.  BCC is the most frequent carcinoma occurring at the region of the body to which radiotherapy is delivered. Patients whose immune status is compromised, particularly recipients of organ transplants are also predisposed to develop these tumors. 
The clinical presentation of BCC can be variable. It may present as a papulonodular lesion with a pearly translucent edge, as an ulcerated destructive lesion (rodent ulcer), a plaque with variable amount of induration, an erythematous plaque with visibly dilated vessels, or as a partly cystic nodule. ,, Aggressive growth tumors care large, show more frequent ulceration, and can be locally destructive of eyes, ears, and nares. , The variable clinical presentation suggests that it is a great mimicker of other lesions.  Most of the BCCs in our study presented as a nodule and were clinically diagnosed as seborrheic keratosis, SCC, sebecous carcinoma (at eyelid), and rarely adnexal tumors. The pigmented nodules were clinical diagnosed as mole, melanoma or seborrheic keratosis. Microscopically these lesions in our series represented nodular BCC s with or without differentiation and pigmented BCCs. Two cases had presented as plaque like lesions which in one case was thought of as spectacle rash.
Microscopically, BCCs comprises islands or nests of basaloid cells, with palisading of the cells at the periphery and a haphazard arrangement of those in the centers of the islands [Figure 1]. Most of the cases show some connection to the under surface of the epidermis. Islands of tumor cells are surrounded by a fibrous stroma and may retract leaving a peritumoral lacuna. A variable inflammatory infiltrate is usually present. ,
|Figure 1: Nodularbasal cell carcinoma showing classical peripheral palisading of cells (H&E x400)|
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There is considerable variability in the morphological spectrum of the BCCs, and as a result, a number of histopathological subtypes have been defined. The morphological subtypes according to the WHO classification include superficial, nodular (solid), micronodular, infiltrating, fibroepithelioma, BCC with adnexal differentiation, basosquamous, and keratotic types.  These types can be divided into undifferentiated and differentiated, with the latter showing differentiation towards hair follicles (keratotic), sebaceous glands, as well as apocrine and eccrine glands (adenoid) illustrated in [Figure 2]. Mixed patterns are quite common, and have been reported from India. 
|Figure 2: Adenoid basal cell carcinoma showing tubular/glandular differentiation (H&E x400)|
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BCCs are also classified as belonging to indolent-growth (low risk) or aggressive-growth (high risk) subsets. The indolent-growth variants include nodular, nodulocystic, and fibroepithelioma types of BCC. The aggressive growth tumors are superficial BCC, micronodular BCC, infiltrative BCC, morpheiform or sclerosing BCC, and metatypical BCC. ,,,, In the present series, most of the cases were of low risk type (21 cases).
The nodular (solid) form was the most common type of BCC in the present study which is in concordance with other studies. These are composed of large lobules of basaloid cells with the typical peripheral palisading of the nuclei. , Pigmentation may be seen in a majority of BCCs but large amounts of melanin are encountered only rarely, and these are called pigmented BCC. Frequency of pigmentation in our study was 64%. One study reported pigmentation in 69% of the non-superficial BCCs. In white races, the frequency of pigmented BCC varies from 6.7% to 33%, which is much lower than that of Asian reports.  The melanin is produced by the benign melanocytes that colonize the tumors. Cystic spaces may form as a result of tumor necrosis or cellular dyshesion.  Superficial BCC is one of the subtypes that presents as erythematous lesions with indolent growth history mimicking many other non-neoplastic skin lesions thus, misleading the clinician.  There were no cases of superficial BCC in the present series.
Keratotic BCC is characterized by the presence of prominent keratin formation [Figure 3]. The keratinization is trichilemmal type which distinguishes it from the keratin pearls of squamous cell carcinoma. , Adenoid type of BCC is a rare histological variant which can morphologically present as pigmented or non-pigmented nodule or ulcer. ,,
|Figure 3: Keratotic basal cell carcinoma showing keratin formation (H&E x400)|
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Basal cell carcinoma with areas of squamous cell differentiation [Figure 4] is described as basosquamous cell carcinoma. The term metatypical carcinoma has also been used synonymously. This controversial diagnosis is accepted by some authors and rejected by others. It is debatable whether a BCC with areas of squamous differentiation or a BCC differentiating into SCC should be called basosquamous cell carcinoma. ,,,, The basosquamous variant of BCC behaves aggressively with higher tendency for metastasis and recurrence compared to typical BCC. Immunohistochemical studies suggest that this variant is a continuum of BCC and SCC, where in BCC undergoes squamous differentiation leading to development of basosquamous carcinoma. 
|Figure 4: Basosquamous carcinoma showing basal cell carcinoma with areas of squamous differentiation (H&E x400)|
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The histopathological features of BCC are characteristic and rarely pose diagnostic challenge. However, in the context of differentiating BCCs from its mimics many studies have been done to explore suitable immnunohistochemical markers. The BerEP4, a keratin marker, is found to be a useful to differentiate keratotic basal cell carcinoma from squamous cell carcinoma. , The squamous cell carcinomas typically stain strongly positive for high molecular weight cytokeratins (HMW), epithelial membrane antigen (EMA), and are BerEP4-. In contrast, the basal cell carcinomas are BerEP4, low molecular weight Cytokeratin (LMW CK), androgen receptor, Bcl-2, CEA, and CD44 antibodies positive. S100 and HMB45 are the two main antibodies used for confirming melanomas. Recently, several other antibodies have been added which includes MART-1 (Melan-A), a more sensitive and specific marker. Others are MAGE-1, Tyrosinase, and Micropthalmia Transcription Factor (MITF). ,
The connective tissue stroma seen proliferating around the tumor often shows numerous young fibroblasts and an inflammatory infiltrate which may be mild to moderate. Retraction of the stroma from the tumor islands results in peritumoral lacunae. Their presence aids in the differentiation of BCC from other tumors. The stroma may also show mucin or amyloid deposits. 
Besides the histological subtype, the risk of local recurrence may be related to the presence of perineural invasion and to the involvement of the excision margin. , Evidence of deep invasion and perineural invasion was very rare in the present study conforming to the natural history of most cases of BCC.
Although most BCCs are slow-growing, relatively non-aggressive tumors, a minority have an aggressive behavior with local tissue destruction and rarely, metastasis. ,, Thus, there are rare instances of BCC eroding into the eye. Metastatic BCC has a reported incidence of only 0.0028-0.5%.  The sites of metastasis include lymph nodes, lungs, bones, and liver. 
| Conclusion|| |
Advances in the biology of BCC have led us to understand the pathways of lesional evolution and its behavior. The impact of the accurate classification of BCC upon therapy has induced clinicians to demand precision as well as accuracy in morphological classification and marginal status of the tumor. Thus, all practicing surgical pathologists should be aware of the histologic criteria for diagnosis and subclassification of this tumor. 
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]