Keloidal basal cell carcinoma after radiation therapy

ARTICLE

Auteur(s) : Noriyuki MISAGO, Yuko OGUSU, Yutaka NARISAWA

Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga 849-8501, Japan

Article accepted on 19/12/2003

In 1996, Requena et al. [1] proposed the term keloidal basal cell carcinoma (BCC) as a new clinicopathological variant of BCC. Keloidal BCC is characterized clinically by keloid-like lesions, occurrence at sites where there has been no previous injury, and histopathological features demonstrating thick keloidal collagen bundles intermingled with characteristic basaloid aggregations of BCC. To the best of our knowledge, after the original report by Requena et al. [1] there have been no additionally reported cases of keloidal BCC except for a description in one textbook [2]. We report on a case of keloidal BCC that developed 60 years after radiation therapy for cervical lymph node tuberculosis.

Case report

A 67-year-old Japanese man presented with a 6-year history of a nodular lesion with a gradual enlargement on his right preauricular region. The patient reported that he had received an unknown amount of radiation therapy over a three-year period for the treatment of right cervical lymph-node tuberculosis when he was 7 years old.
On examination he had an area of chronic radiation dermatitis showing atrophy, telangiectasia, and irregular hyper- and hypopigmentation, which included the right side of the cervical, auricular, preauricular and buccal regions. Within the area of chronic radiation dermatitis, on the right preauricular region, he presented with a 1.6 × 1.2 cm-sized skin-colored to erythematous, firm nodule that was hyperkeratotic and had a crusted surface. Characteristically, numerous folded wrinkles radiated out from the nodule (Fig. 1). There was no history of previous injury in this area. There were no features of Gorlin syndrome, in which radiation-induced BCC is frequently seen. Based on a diagnosis of radiation-induced squamous cell carcinoma (SCC), the nodular lesion was completely excised. Neither recurrence nor metastasis has been observed during 3.5 years of follow-up. The surgical scar was normal.
Histopathologically, a scanning view demonstrated a relatively well-defined nodular lesion involving an area from the whole dermis into the subcutaneous tissue that was covered by parakeratotic epidermis (Fig. 2A). The nodular lesion was mainly composed of dense collagenous stroma, which contained irregular, jagged, and spiky cords and strands of basaloid cells. These irregular cords and strands were predominantly distributed in the periphery of the nodular lesion.
The surrounding skin of the nodular lesion showed the features of chronic radiation damage such as irregularly pigmented and atrophic epidermis (hyperplastic in some areas), and telangiectatic vessels in the upper dermis. Although no radiation-induced fibrosis was seen, severe actinic elastosis was observed in the surrounding dermis. The dense collagenous stroma containing neoplastic cords and strands was well demarcated from the surrounding actinic-damaged dermis (Fig. 2B).
The dense collagenous stroma of the nodular lesion typically showed bright, eosinophilic, prominent thickened, keloidal collagen bundles (Fig. 3A). Although the basaloid, neoplastic cords and strands usually showed poorly developed peripheral palisading, some basaloid aggregations and cords beneath the epidermis demonstrated the prominent peripheral palisading and mucinous retraction spaces that is typical for BCC (Fig. 3B).

Discussion

In their original report, Requena et al. [1] demonstrated two cases of keloidal BCC with case 1 clinically showing a nodular lesion with a keloidal appearance on the parotid region and case 2 manifesting as a nodular lesion covered by keratotic crust resembling SCC. The latter case is similar to the case presented here. Histopathologically, the scanning views of the keloidal BCCs in both the two original cases and in our present case were highly characteristic as the prominent, keloidal, thickened collagen bundles stood out against collagen bundles of the surrounding normal or actinic-damaged dermis. Additionally, the well-circumscribed, keloidal collagen bundles proliferated in a nodular form clinically mimicking a firm, nodular lesion. The basaloid aggregations of BCCs were distributed within the keloidal collagens. The present case also resembles the second case reported by Requena et al. [1] histopathologically because the basaloid aggregations of BCC were mainly distributed within the peripheral area of the nodular, keloidal stroma.
Keloidal BCC differs from morpheiform BCC, as the morpheiform type is not associated with well-circumscribed, keloidal collagen bundles that proliferate in a nodular form and result in a nodular clinical appearance [1]. Morpheiform BCC clinically shows a plaque lesion, narrow strands or cords of BCC, which are embedded in an ill-defined, dense fibrous stroma. The stromas observed in morpheiform BCC are not keloidal and are accompanied by a coordinate increase in type I and type III procollagen mRNA levels [3]. The ratio of type I to type III collagen has been reported to be significantly increased in keloids [4], whereas it is generally considered to be decreased in scar tissue [5, 6] and radiation-induced fibrosis [7, 8]. Nevertheless, the ratio of type I to type III collagen in neoplastic stroma should be different between keloidal BCC and morpheiform BCC.
Cases of post-irradiation morphea have also been reported [9-11]. But the histopathological changes in these cases consisted of just sclerotic collagen bundles with no basaloid epithelial aggregations between them, in contrast with keloidal BCC.
Requena et al. [1] speculated that the characteristic stroma in keloidal BCC may result from a localized loss of control of the extracellular matrix production by fibrocytes and reduced degeneration of the newly synthesized procollagen polypeptides. Because irradiated fibrocytes have been reported to show premature terminal differentiation and increased collagen production [12, 13], it cannot be completely denied that the irradiation 60 years earlier played some part in the keloidal stroma in the present case. However, this factor was not considered to be of a primary concern because no radiation-induced fibrosis was observed in the keloidal BCC-surrounding dermis and the nature of collagen was different between the radiation-induced fibrosis and the keloidal stroma as mentioned before.
Low doses of radiation have been suggested to induce the development of BCC more frequently than SCC [14, 15], and the development of BCC following radiation therapy for benign diseases is well documented [16-22]. These benign diseases include acne vulgaris, hirsutism, eczematous dermatitis, hemangioma, and tinea capitis, etc. [16-22]. The reports of the development of BCC following radiation therapy for tuberculosis such as in the present case have only rarely been seen [19-21].
The median interval between radiation exposure and diagnosis of skin cancers (mainly BCCs) has been reported to be 21 years (ranging from 4 to 64 years) [17]. The radiogenic BCCs usually occur within the area of chronic radiation dermatitis, although they sometimes develop within an area without any clinical evidence of chronic radiation damage [16, 20]. The present BCC developed within the area of chronic radiation dermatitis as evidenced by irregularly pigmented and atrophic epidermis, and telangiectasia in clinicopathological terms. The radiogenic BCCs tend to be multiple [16-24], and they manifest as conventional nodular BCC [18, 19, 22, 24], superficial BCC [18-20, 23, 24], and, rarely, fibroepithelioma Pinkus type [18]. Keloidal BCC after radiation therapy as in the present case is highly exceptional. The risk of the radiogenic BCCs is suggested to increase with a lower age of exposure [14] and by additive ultraviolet radiation [14, 21]; being considered to correspond to the present case. However, the influence of previous radiotherapy in the histogenesis of this BCC is doubtful, because radiotherapy was administered many years before the development of the neoplasm and, on the other hand, BCC is so frequent in sun-damaged skin of elderly patients that is difficult to know the influence of other etiologic factors in the genesis of this neoplasm.
To date there is no universally agreed upon classification of BCC, and the classification that has been worked out based on the various viewpoints include such items as clinical appearance, histopathology, growth pattern, cytology, and differentiation, etc. The classification by growth pattern has been recently recommended because it correlates with clinical behavior and treatment required, and as a consequence is useful in clinical practice [25, 26].
Since the irregular, jagged, and spiky neoplastic aggregations are distributed within the stroma in keloidal BCC, keloidal BCC may belong to the high-risk group of BCCs such as infiltrative/morpheiform BCCs. However, subclinical extension of keloidal BCC is considered not to be as prominent as infiltrative/morpheiform BCCs because of the well-circumscribed, keloidal stroma containing neoplastic aggregations.
From a clinicopathological viewpoint, BCCs can be classified into five types; nodular, superficial, morpheiform, infundibulocystic, and fibroepithelioma Pinkus types [2]. However, due to its unique clinicopathological features, keloidal BCC can be said to be a rare variant of morpheiform BCC, or it belongs in a different category from the five previously reported types. n

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