J Clin Pathol 1985;38:1273-1277

Basal cell carcinoma of the skin with areas ofsquamous cell carcinoma: a basosquamous cellcarcinoma?J LOPES DE FARIA

Department ofAnatomical Pathology, Faculdade de Ciencias Medicas, UNICAMP, Campinas, SP, Brazil

SUMMARY The diagnosis of basosquamous cell carcinoma is controversial. A review of cases ofbasal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma.This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a

comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma.Areas of intermediate tumour differentiation between basal cell and squamous cell carcinomawere found. Basal cell carcinomas with areas of squamous cell carcinoma may be called baso-squamous carcinoma.

Basal cell carcinomas have been described with nuc-lear atypia,' multinucleate tumour giant cells,' 2 andother unusual or aggressive features.3 Only one caseof basal cell carcinoma with areas of squamous cellcarcinoma has been reported, and this was termedbasosquamous cell carcinoma.4 This controversialdiagnosis is accepted by some authors-8 andrejected by others.9-'2 This paper reports a his-topathological study of 23 cases of basal cell car-cinoma of skin in which there were conspicuousareas of squamous cell carcinoma.

Material and methods

Over five years (1974-8) we diagnosed histologi-cally 409 cases of basal cell carcinoma (BCC) of theskin. Thirteen cases had areas of squamous cell car-cinoma; 10 new cases with this feature were diag-nosed subsequently, making a total of 23 cases. Allthe patients were white, in the fifth to eighth decadesof life, and comprised 14 men and nine women. Allthe tumours occurred in areas exposed to the sun;18 were on the face. In most cases the skin wasulcerated at the time of clinical examination. Sevenpatients had an additional skin carcinoma else-where, five of which were BCC and two squamouscell carcinomas (SCC). We compared 40 cases ofsolid BCC and 40 of keratotic BCC, as defined byLever and Schaumburg-Lever,9 as controls. Thesecontrol cases were studied sequentially, providedthere was sufficient material for a suitable histologi-cal analysis.Accepted for publication 1 July 1985

Nine surgical specimens of BCC with areas ofSCC were about 5 mm long, and 14 specimens com-prised the entire tumoral mass, and these were allexamined histologically. The material was embed-ded in paraffin, and sections were stained withhaematoxylin and eosin, and occasionally with stainsfor reticulin. In most patients one section from oneor more blocks was examined. In a few cases serialsections were also used.The aggressiveness of basal cell carcinomas and

BCCs with areas of SCC was defined by the pres-ence of small cell clusters with spikey outlines andinfiltration of cells in cords one and two cells thick.3Statistical evaluation of the results was done usingthe x2 test.

Results

CONTROL GROUPSBasal cell carcinoma ofsolid typeThe tumours showed the characteristic pattern ofcompact lobular BCCs9 and consisted of masses ofdark staining small cells, with palisading of thesecells at the periphery. The cells had little cytoplasmand uniform nuclei. In 29 of 40 patients (73%) therewere a few small cell masses with irregular outlinesassociated with infiltration of cells in cords one ortwo cells thick. A few cell masses in 12 of 40 cases(30%) exhibited occasional atypical cells with verylarge vesicular nuclei, scanty cytoplasm, and promi-nent nucleoli (Fig. 1). Mitoses were rare.Keratotic basal ceUl carcinomaThe pattern was similar to that of compact lobular

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Fig. 1 Control patient with solid basal cell carcinoma.Cluster ofbasal cell carcinoma has cells with large vesicularnuclei (arrow) and spikey outline. (Hematoxylin and eosin.)x 300.

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Fig. 2 Control patent with basal cell carcinoma withdifferentiation ofsquamoid cells and rare parakeratotic cells(arrow). Notice palisading and uniform appearance ofcells.(Hematoxylin and eosin.) x 384.

BCCs, with frequent peripheral palisading. In thecentre of the tumour islands there was, however,differentiation of basal cells into intermediate cellswith amphophilic cytoplasm and into parakerototicand keratotic squamous cells (Fig. 2). The keratoticcells were single or grouped into "pearls"'. The nuc-lei, in general, varied little in size and staining. Cellmasses with infiltrative borders, with the infiltrationof cells in cords one to two cells thick, were lesscommon than in the compact lobular type of BCC;they were seen in 24 of 40 patients (60%). Atypicalcells were detected in half the patients (Fig. 3). Mit-oses were rare.

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Fig. 3 Controlpadent with basal cell carcinoma. Cluster ofbasal cell carcinoma shows darkly stained palisading to theleft and differentiation ofsquamoid cells; on the rightatypical cell with large nucleus and scanty cytoplasm(arrow). (Hematoxylin and eosin.) x 384.

Two cases with atypical cells exhibited a specialfeature: in addition to features of compact lobularBCC with areas of keratotic BCC, there was alsoone large solid cell mass in each. This consisted oflarger and paler staining monotonous intermediatecells with amphophilic cytoplasm, which had littlevariation in nuclear size but had more numerousatypical cells than those in BCCs of compact lobulartype. Palisaded basal cells were found only in part ofthe periphery of these cell masses.

BASAL CELL CARCINOMAS WITH AREAS OFSQUAMOUS CELL CARCINOMAThe prevalence of basal cell carcinomas of the skinwith areas of squamous cell carcinoma in this serieswas 3% (13 of 409 patients). All but four tumourswere ulcerated. The tumours had infiltrated thereticular dermis, and some extended as far as stri-ated muscle. The inflammatory reaction in the tissuearound the tumour cells consisted mainly of lym-phocytes and plasma cells and was rarely severe.Connective tissue proliferation was usually moder-ate.

In the same section of each specimen there weredistinct areas of BCC, SCC, and an intermediatestage of differentiation (Figs. 4 to 10). Most of thetumour comprised BCC with smaller areas of inter-mediate tissue and occasional areas of SCC. Thebasal cell carcinoma was solid in eight cases, kerato-tic in nine, and mixed in six (solid and keratotic inthree; solid and adenoid in two; and solid, adenoid,and keratotic in one). Adenoid areas of BCC in themixed type presented the characteristic features of

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Basal cell carcinoma of the skin with areas ofsquamous cell carcinomaa .\-N at ..5*.'fo3, I--S^*g;@b_X yf<) ;

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dnis. (aros) 96Fig. 6 Basal cell carcinoma with poorly delineated area ofsquamous cell carcinoma seen between the arrows.(Hematoxylin and eosin.) x 20.

Fig. 5 Higher magnification ofFig. 4 from area indicated Fig. 7 Higher magnification ofFig. 6, ofarea indicated byby left arrow, showing adenoid tissue to the right and left arrow, showing basal cell carcinoma on the left andsquamous cell carcinoma to the left. Squamous cels present squamous cell carcinoma on the right. x 80.very large, and light nuclei with prominent nucleoli

-I _...;1::__.1v22A(arrows), ana aciaopnmuc cyopiasm. x .

adenoid basal cell carcinoma,9 and were continuouswith the areas of SCC (Figs. 4 and 5).The areas of squamous cell carcinoma were small

and isolated in two thirds of patients, but in theremainder there were two, three, and occasionallyfive areas of SCC. The size of the squamous areas

was generally smaller than that of the areas of BCCor of the intermediate carcinomatous tissue. Thesize of each area did not usually exceed one field at amagnification of 100 x and was sometimes as smallas one field at a magnification of 400 x. The areas ofSCC were not related to ulceration and were seendeep in the reticular dermis and in striated muscle.

Even the smallest tumour islands had the typicalpattern of SCC of the skin, (Figs. 5, 6 and 8). Theseareas consisted of squamous cells with large nucleiand little cytoplasm. The nuclei showed variation insize and staining. The classification of the SCC inthese areas was: grade 2, nine patients, grade 3, 11,grade 4, three.9The tumour areas which were of intermediate dif-

ferentiation were abundant and differed in part fromthose of typical BCC of the solid or keratotic type orSCC. Aggressive features were common and similarto those described in BCCs. Peripheral palisading ofbasal cells was, however, generally absent (Fig. 9).The tumour cells with intermediate differentiationwere larger and lighter compared with those of

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Fig. 8 Higher magnification ofFig. 7, ofarea iWidicated byarrow, showing squamous cell carcinoma with infiltration of

single cells. x 320.

Fig. 9 Higher magnification ofFig. 6 ofarea indicated byright arrow. Note monotone appearance of intermediatestage carcinomatous tissue without palisading on the left andcells with large nuclei (arrow). x 320

compact lobular BCC; this was due to differentia-tion into cells with amphophilic cytoplasm or, more

rarely, into cells with eosinophilic cytoplasm. Largeand atypical cells, as seen in control basal cell car-

cinomas, were present in the intermediate tumourtissue of all patients but were more common than inthe controls. Mitoses were common in the inter-mediate tumour tissue in a few patients.Basal cell carcinomas with areas of SCC had a

greater prevalence of aggressive features (78%)compared with the compact lobular, or keratotic tis-sue of BCCs (39%). The difference was significant(p < 0-01). A similar difference in the prevalence ofaggressive features was also seen between the con-

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Fig. 10 Higher magnification ofFig. 6 ofarea (bottomright) showing typical picture ofbasal cell carcinoma(palisading at the top) x 320.

trol BCCs with and without cell atypia (65% v 40%,p < 0-05). The control specimens were of both thecompact lobular and keratotic types.

Discussion

In spite of the prevalent aggressive features andatypia of single cells in BCCs of compact lobu-lar, or solid, and keratotic types, the change of thesetumours into SCCs rarely occurred (3%). In kerato-tic BCC the cell masses consisted of basal cells withsquamous differentiation towards their centre; bothbasal and squamous cells were often uniform inappearance (Fig. 2). It must be said that the areas ofSCC were not related to the epidermis or ulceration.They were deeply located, and exhibited the con-spicuous pattern and cellular features of SCC (Figs.7 and 8) rather than those of keratotic BCCs.

It is debatable whether a BCC with areas of SCCshould be called basosquamous cell carcinoma. Asprevious studies have not provided an exactdefinition of a basosquamous carcinoma4 it isdifficult to compare our findings with data fromother authors. Exception is made for Burston andClay,4 who defined the basosquamous carcinoma asa BCC differentiating into SCC. If their view isaccepted the tumours reported here could also becalled basosquamous carcinomas. Perhaps, for thetime being, it would be better to use the descriptiveterm "basal cell carcinoma with areas of squamouscell carcinoma". The term " mixed carcinoma of theskin" is reserved for a tumour with two parts, one ofBCC and the other of SCC, with both parts appar-ently independent in origin.9 In these tumoursintermediate tumour is absent.

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Basal cell carcinoma of the skin with areas ofsquamous cell carcinoma

The nature of this intermediate tissue is not fullyunderstood. I considered it to be a transitional tissueand not an area of BCC with atypical cells. Thistheory is supported by the following features: dif-ferentiation of intermediate tumour into characteris-tic SCC; absence of peripheral palisading in mostcell masses; more numerous atypical cells; and moreinfiltration borders. The local aggressiveness in thetransitional carcinomatous areas was greater thanthat of typical BCCs (p < 0.02).The finding in two patients of keratotic BCC were

similar to those of intermediate tissue. These casesmay imply that BCCs with incomplete change intoSCCs do exist.

If a BCC has small areas of SCCs these areas maygo unnoticed in a routine biopsy. As the intermedi-ate carcinomatous tissue is usually much moreabundant the finding of this tissue should compel asearch for areas of SCC.The relation of BCC with areas of SCC to metas-

tasising basal cell carcinomas requires further study.The metatypical pattern in metastasising BCC'3 issimilar to the transitional carcinomatous tissue out-lined in this study.

References

Okun MR, Blumental G. Basal cell epithelioma with giant cellsand nuclear atypicality. Arch Dermatol 1969; 89:588-600.

2 Rupec M, Vallilzadh F, Korb G. Uber das Vorkommen vonmehrkernigen Riesenzellen in Basaliomen. Arch Klin ExpDermatol 1969;235: 198-202.

Jacobs GH, Rippey JJ, Altini M. Prediction of aggressivebehaviour in basal cell carcinoma. Cancer 1982;49:533-7.

4Burston H, Clay RD. The problems of histological diagnosis inbaso-squamous cell carcinoma of the skin. J Clin Pathol1959; 12:73-9.

Montgomery H. Basal squamous cell epithelioma. Arch Der-matol 1928; 18:50-73.

6 Gans 0, Steigleder G-K. Histologie der Hautkrankleiten. Vol II.Berlin: Springer Verlag, 1957:332.

Borel DM. Cutaneous basosquamous carcinoma. Review of theliterature and a report of 35 cases. Arch Pathol Lab Med1973;95:293-7.

Haber H, Symmers WStC. The skin. In: Symmers WStC, ed.Systemic pathology. Vol VI. 2nd ed. London: Churchill Living-stone, 1980:2596.

Lever WF, Schaumburg-Lever G. Histopathology ofthe skin. 6thed. Philadelphia: JB Lippincott, 1983.

'° Pinkus H, Mehregan AH. Tumoren der Haut. In: Doerr W,Seifert G, Uehlinger E, eds. Spezielle pathologische Anatomie.Vol VII. Berlin: Springer Verlag, 1973:559-65.

"Allen AC. Skin. In: Anderson WAD, Kissane JM, eds. Pathol-ogy. Vol II. 7th ed. St Louis: CVB Mosby, 1977:1802-73.

12 Ashley DJB. Tumors of the Integument. In: Ashley DJB, ed.Evan's histological appearances of tumours. 3rd ed. Edin-burgh: Churchill Livingstone, 1978:342-436.

3 Farmer ER, Helwig EB. Metastatic basal cell carcinoma:clinicopathologic study of 17 cases. Cancer 1980;46:748-57.

Requests for reprints to: Dr J Lopes de Faria, Departmentof Anatomical Pathology, Faculdade de Ciancias Medicas,UNICAMP, Campinas, SP, Brazil.

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