Numerous Basal Cell Carcinoma: A Case Report in a Suspected

Nonsyndromic Patient

Arinia Kholis Putri

, Adhimukti T. Sampurna

, Larisa Paramitha Wibawa

, Roro Inge Ade Krisanti

Departement of Dermatology and Venereology Faculty of Medicine Universitas Indonesia, Dr. Cipto Mangunkusumo

National General Hospital, Jakarta, Indonesia

Keywords: Basal cell carcinoma, numerous, multiple, nonsyndromic, nonmelanoma skin cancers

Abstract: Basal cell carcinoma (BCC) is the most common cancer in humans. BCC usually occurs as a solitary lesion

on sun-exposed areas. Various syndromes have been defined in which basal cell carcinoma exists in multiple

localizations in a single patient. Multiple BCC is often related with inherited conditions such as Gorlin

syndrome, Rombo syndrome, etc. Multiple BCC without history and clinical examination that are not

consistent with those syndromes is considered as nonsyndromic BCC. It is still unclear what environmental

and genetic factors contribute to the development of multiple nonsyndromic BCC. A case of numerous basal

cell carcinoma with multiple localizations without signs and symptoms which is classified as a syndrome is

described in this case report. Dermoscopic evaluation aids the diagnosis of and evaluation for people with

history of nonmelanoma skin cancer.

1 INTRODUCTION

BCC is the most frequent cutaneous neoplasm, with

slowly progressive nature and locally invasive

behavior, that arise from non-keratinizing cells within

the basal layer of the epidermis (Tcherney et al.,

2017; Carucci et al., 2012; Totonchy and Leffell,

2017). The malignancy accounts for approximately

75% of all nonmelanoma skin cancers (NMSC) and

almost 25% of all cancers diagnosed in the United

States (Carucci et al., 2012).

BCC usually occurs as a solitary lesion on sun-

exposed areas. There have been very few cases

reported in the literature so far of multiple BCC. This

condition occur mostly in several genetic syndromes,

but can also happens as a sporadic feature. Among

several syndromes, the most commonly known is

Gorlin syndrome or nevoid basal cell carcinoma

syndrome, an autosomal dominant trait caused by

PTCH gene mutation (Satolli et al., 2018). It is still

unclear what environmental and genetic factors

contribute to the development of multiple

nonsyndromic BCC (Tcherney et al., 2017). Risk

factors for BCC have been well characterized

(Totonchy and Leffell, 2017). The most significant

risk factor involved in the pathogenesis is ultraviolet

(UV) which triggers mutations in tumor suppressor

genes (Kim et el., 2017). Increasing age, male, white

race, exposure to ionizing radiation, arsenic, and

polyaromatic hydrocarbons have also been correlated

with higher rates of BCC (Totonchy and Leffell,

2017; Kim et al., 2017). Both genetic predisposition

and exposure to environmental risks are involved in

the pathogenesis of the malignant transformation in

BCC (Tcherney et al., 2017). The early detection and

eradication of these tumors are of importance for

treatment effectiveness and quality of life because

BCC could have an aggressive course and behavior

which can lead to severe disfiguration and destruction

(Tcherney et al., 2017; Carucci et al., 2012; Totonchy

and Leffell, 2017; Kim et al., 2017).

BCC comprising several lesions is not

uncommon, but nonsyndromic with numerous lesions

are rare entities. We present a patient, came with

numerous BCC without any signs and symptoms of a

specific syndrome as we discuss the potential

triggering risk and the further appropriate therapeutic

options.

2 CASE

A 56-year-old female patient with Fitzpatrick skin

type IV was admitted to the dermatological unit with

a complaint of three ulcerated pigmented skin lesions

with painless sensation on the face. The patient had

428

Putri, A., Sampurna, A., Wibawa, L. and Krisanti, R.

Numerous Basal Cell Carcinoma: A Case Report in a Suspected Nonsyndromic Patient.

DOI: 10.5220/0008159004280432

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 428-432

ISBN: 978-989-758-494-7

previously received Mohs micrographic surgery

(MMS) for a BCC lesion, with diameter

approximately 3 cm, on the upper lip at our hospital 4

years ago. But she was loss to follow up after the

treatment for the flap from plastic reconstruction

surgery unit. The patient was a scavenger and was

constantly exposed to direct sunlight for most of her

lifetime. She denied any history of sunburn, family

history of skin cancer, past history of radiotherapy,

and exposure to chemical substances including

arsenic.

She had hypertension, which is controlled with

medications and showed no regional

lymphadenopathy. The laboratory blood tests and

imaging diagnostic procedures did not revealed any

abnormalities nor signs for systemic involvement. No

symptom and sign such as mandibular cyst, palmar

and plantar pitting, skeletal abnormalities,

keratocystic odontogenic tumors, ectopic

calcification of the dura, macrocephaly, and mental

retardation.

On physical examination of the face, three

ulcerations were observed, one measuring

approximately 1 x 1 x 0,5 cm located on the tip of her

nose. The second and third one measuring

approximately 1,5 x 1 x 0,5 cm and 0,5 x 0,5 x 0,1 cm

were located on the right cheek. Those three lesions

showed pigmented pearl-like edges, bleeding surface,

and irregular borders. These lesions were in

accordance clinically, dermoscopically, and

histopathologically for BCC in different stages of

invasion (figure 1). We also found 21 pigmented

lesions on her face and head, also 54 pigmented

lesions were noted on her neck, which she did not

notice nor have any complaints. All of these lesions

have size ranging from 0,4 mm to 1,5 cm and

demonstrated similar clinical signs such as irregular

borders with pearl-like edges, with dermoscopic

appearance also suggestive for BCC (Figure 2b – g).

Electrosurgery was performed for more than

twenty superficial tumors on the neck. After the

procedure, the wound sites were re-examined using a

dermoscope to ensure there were no visible

pigmented lesions left. Furthermore, the patient is still

regularly come to our clinic to remove her remainder

BCC lesions gradually with excision and

electrosurgery. We plan to do periodic checkup for

early detection of NMSC after all the lesions are

removed.

3 DISCUSSION

BCC is the most common human cancer that usually

occurs as a single lesion. The vast majority of BCC

were located on the head and neck (Carucci et al.,

2012; Kim et al., 2017). Recent reports show that the

number of patients who develop more than one BCC

is increasing (Tcherney et al., 2017). According to the

clinical, dermoscopic, and histopathologic findings,

our patient was diagnosed as having multiple BCC

that mostly located on the scalp, nose, and neck.

Multiple BCCs are not uncommon as there is a 36%–

50% increased risk of development of additional

BCCs after the first lesion within 5 years (Kim et al.,

2017). The total number of NMSC is a risk factor for

recurrence of previous tumor, as well as for the

formation of new ones (Tcherney et al., 2017). This

patient also had a history of MMS for a large BCC on

her upper lip 4 years ago.

UV is thought to be the most important

environmental factor in its pathogenesis, although it

is not always possible to correlate the sites where

exposure is most intense to those where lesions are

most frequently found (Kobacas et al., 2010). An

Italian study indicated the important role of sunburns,

and therefore intense sun exposure, rather than that of

prolonged sun exposure to increase the risk of BCC

(Tcherney et al., 2017). Increasing age, Northern-

European ancestry, male, immunosuppression, and

arsenic exposure are the other established risk factors

(Carucci et al., 2012; Kim et al., 2017). Our patient

was 56 year-old female with Asian descendant.

Although she is a scavenger and was constantly

exposed to direct UV for most of her lifetime, she has

Fitzpatrick skin type IV which rarely burns and tans

easily, and denied any history of sunburn. Other

factors include exposure to ionizing radiation,

arsenic, and polyaromatic hydrocarbons, which

appear to be involved in mutations of regulatory

genes and alterations in immune surveillance

(Carucci et al., 2012; Kim et al., 2017). From history

taking this patient denied exposure of ionizing

radiation, arsenic, and polyaromatic hydrocarbons.

Numerous Basal Cell Carcinoma: A Case Report in a Suspected Nonsyndromic Patient

429

Figure 1. Preoperative photography shows that the lesions (circles) were located on the face (a-c). Dermoscopy appearance

showed ulceration, leaf-like structures, blue-black globules and dots, and arborizing vessels (d-f). Histopathology with

hematoxylin and eosin (H&E) staining with 40x magnification, showed the 3 lesions have basaloid epithelium with peripheral

palisade layer under an ulcerated epidermis, with artefactual cleft, and mucinous stroma deposit on the border and central

tumors (g-i)

Figure 2. Pigmented lesions (circles) were located on the neck (a). Dermoscopy appearance showed leaf-like structures, blue-

black dot, globules, and arborizing vessels (b-g).

Inherited conditions such as the nevoid BCC

syndrome (Gorlin syndrome), Rombo syndrome,

unilateral basal cell nevus syndrome, and Bazex

syndrome are common inherited conditions with

multiple BCC manifestations. Nonsyndromic but

hereditary multiple BCC have been reported in

literatures, but they were ruled out based on the

negative family history (Tcherney et al., 2017; Kim et

al., 2017). In our case, history and clinical

examination were not consistent with these

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

430

syndromes that related to multiple BCC. Also, there

was no sign and symptom of the lesions at a younger

age, nor a positive family history. Thus, this case does

not fit into any of the syndromes seen with basal cell

carcinoma such as Gorlin syndrome or Bazex

syndrome. There was no history of exposure to

arsenic, irradiation, dry ice and no evidence of

keratoacanthoma or xeroderma pigmentosum in this

patient. However, considering the financial status of

the patients, we could not perform polymerase chain

reaction (PCR) assay to rule out this genotype.

Moreover, the treatment plan would not be affected

by the PCR result. Hence, we categorized our cases

as nonsyndromic and nonhereditary type of multiple

basal cell carcinomas worth mentioning.

In some literature, multiple BCC in one patient

increases the risk of recurrence and they often

develop new BCC with similar or different

histological appearance (Tcherney et al., 2017). As

also proven, not all instances of multiple BCC are due

to genetic syndromes. Multiple superficial BCCs

without associated anomalies are distinct from the

Gorlin syndrome and could be explained by an

autosomal dominant phenotype. Alternatively, this

nonsyndromic phenotype might have a polygenic

basis. Furthermore, a recent article has revealed that

multiple BCC can be also part of the BAP 1 mutation

(Satolli et al., 2018). We concluded that our patient

had a high number of basal cell carcinoma lesions

without a syndrome.

Despite the low metastatic potential, local tissue

destruction and disfigurement caused by the tumor

can be enormous if not completely eradicated by early

diagnosis and treatment (Tcherney et al., 2017). Most

basal cell carcinomas can be treated with any of a

number of treatment modalities, including

electrodessication and curettage, cryosurgery,

surgical excision, or MMS. While surgical

interventions such as MMS and surgical excision are

the standard of care and yield the highest cure rates,

the number of non-surgical interventions approved

for the treatment of BCC continues to expand

(Totonchy and Leffell, 2017). Standard surgical

excision with 4-mm margins is the recommended

treatment for BCC with non-aggressive histology,

size of less than 2 cm, and occurrence on low-risk

sites where tissue sparing is not critical (trunk and

extremities). BCC of the face demonstrates high rates

of incomplete excision, and greater efficacy has been

demonstrated using MMS as compared with standard

excision. MMS is recommended in cases of

aggressive histology, recurrent BCC, critical areas of

skin (head, neck, genitalia, hand/feet, nipples) and for

tumors of large size (more than 2 cm) (Totonchy and

Leffell, 2017; Fahradyan et al., 2017).

Current management options are numerous and

focus on tumor eradication while maximizing

cosmetic and functional capacity. The choice of

treatment depends on the tumor type, tumor location,

cost, recurrence rates, and potential cosmetic

disfigurement (Kocabas et al., 2010). Our patient was

treated with 3-4 mm margin excision and performing

histopathologic examination, for lesions that were

bigger than 1 cm on high risk area. But for

approximately 20 small superficial lesions less than 1

cm in size, located not on the high risk area, and

demonstrated with leaf-like structures and arborizing

vessels with the dermoscope, we performed

electrosurgery. After the procedure, the wound sites

were re-examined using a dermoscope to ensure that

there were no visible lesions left. Excision and

histopathology examination for all the BCC lesions

will not be cost-effective for this patient. The early

detection and eradication of these tumors are of

importance for treatment effectiveness and quality of

life (Kim et al., 2017). The patient were asked to

avoid sun-exposure as much as she could possible do.

We plan to do regular checkup for this patient for the

rest of her life to early detection of NMSC.

4 CONCLUSIONS

We have described a patient with multiple

nonsyndromic basal cell carcinoma and had

undergone Mohs micrographic surgery, wide

excision, and electrosurgery. The early detection and

eradication of these tumors are of importance for

treatment effectiveness and quality of life. Our case

illustrates the importance of diagnose and treatment

multiple basal cell carcinoma at early stage.

Performing dermoscopic evaluation will improve in

early detection of BCC.

REFERENCES

Carucci, J.A., Leffell, D.J., Peetersen, J.,2012. Basal cell

carcinoma. In: Goldsmith LA, Katz SI, Gilchrest BA,

Paller AS, Leffell DJ, Wolf K, eds. Fitzpatricks’s

dermatology in general medicine. 8th edition. New

York: McGraw-Hill, p.1294-303.

Fahradyan, A., Howell, A., Wolfswinkel, E., Tsuha, M.,

Sheth, P., & Wong, A., 2017. Updates on the

management of non-melanoma skin cancer (NMSC). In

Healthcare (Vol. 5, No. 4, p. 82). Multidisciplinary

Digital Publishing Institute.

Numerous Basal Cell Carcinoma: A Case Report in a Suspected Nonsyndromic Patient

431

Kim, D.H., Ko, H.S., Jun, Y.J., 2017. Nonsyndromic

multiple basal cell carcinomas, 18(3), pp. 191-196.

Kocabaş, E., Ermertcan, A. T., Bilaç, C., Bilaç, D. B., &

Temiz, P., 2010. Nonsyndromic multiple basal cell

carcinomas successfully treated with imiquimod 5%

cream. Cutaneous and ocular toxicology, 29(4),pp.

300-302.

Pellegrini, C., Maturo, M., Di Nardo, L., Ciciarelli, V.,

Gutiérrez García-Rodrigo, C., & Fargnoli, M., 2017.

Understanding the molecular genetics of basal cell

carcinoma. International journal of molecular sciences,

18(11), pp. 2485.

Satolli, F., Rovesti, M., De Felici, M. B., Zucchi, A.,

Pagliarello, C., & Feliciani, C., 2018. Multiple Basal

Cell Carcinoma Arising in a Verrucous Epidermal

Naevus: Clinical, Histological and Therapeutic

Observations. Acta dermato-venereologica, 98(1-2),

132-133.

Tchernev, G., Pidakev, I., Lozev, I., Lotti, T., & Wollina,

U., 2017. Multiple nonsyndromic acquired basal cell

carcinomas. Wiener Medizinische Wochenschrift,

167(5-6), pp. 134-138.

Totonchy, M., & Leffell, D., 2017. Emerging concepts and

recent advances in basal cell carcinoma.

F1000Research, 6, 1-10.

Verkouteren, J.A.C., 2015. Common variants affecting

susceptibility to develop multiple basal cell carcinomas.

Journal of Investigative Dermatology, 135, 2135–2138.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

432