Basaloid carcinoma ofthe - Journal of Clinical Pathologyjcp.bmj.com/content/jclinpath/20/2/128.full.pdf · true basal cell carcinoma of the peri-anal skin were ... Basaloidcarcinoma

J. clin. Path. (1967), 20, 128

Basaloid carcinoma of the anal canalLILLIAN S. C. PANG AND B. C. MORSON

From the Research Department, St. Mark's Hospital, London

SYNOPSIS The pathology and results of treatment of 36 cases of basaloid carcinomas of the analcanal are described. This variant of squamous cell carcinoma of the anal region arises from theentodermal-ectodermal junctional zone of the anal canal at or above the dentate line. Basaloidcarcinomas have histological characteristics which resemble basal cell carcinoma of the skin, inparticular the presence of palisading of the nuclei at the periphery of the clumps of tumour cells,but are potentially metastasizing tumours. They have been subdivided into three grades of malig-nancy, namely, well-differentiated, moderately differentiated, and anaplastic basaloid carcinoma.It has been shown that cases of well-differentiated and moderately differentiated basaloids have a

good prognosis even when lymph node metastasis has already taken place. Those of anaplasticbasaloid carcinoma have a very poor prognosis even in the absence of lymphatic metastases.

The term 'basaloid' was used by Wittoesch, Wool-ner, and Jackman (1957) to describe certain tumoursof the anal canal which showed a histologicalresemblance to basal cell carcinoma of the skin. In1960, Lone, Berg, and Stearns found that thesebasaloid carcinomas had a better prognosis thanother squamous cell carcinomas of the anal canal.The object of this paper is to describe the pathologyand results of treatment of 36 cases of basaloidcarcinoma of the anal canal seen at St. Mark'sHospital during the years 1928-64.

MATERIAL AND METHODS

This study is part of a review of all malignant tumoursof the anal canal, some results of which have beenreported in previous papers (Morson 1960; Morson andVolkst&dt, 1963 a and b). The basaloid tumours wereidentified amnong 206 carcinomas of the anal canal andanal margin seen at St. Mark's Hospital during theperiod 1928-64. Malignant melanoma, muco-epider-moid carcinoma, adenocarcinoma of the anal canal, andtrue basal cell carcinoma of the peri-anal skin wereexcluded.

In those patients treated by excision of the rectum thesurgical specimens were prepared by cutting along theanterior aspect and stretching them out on a metalframe. The specimens were all photographed and theextent of spread assessed by anatomical dissection andmicroscopy. Because of this routine method it has beenpossible to locate the site of origin ofmost of the tumours.In particular the relationship of the tumour to the dentateline of the anal canal was recorded.

Received for publication 1 September 1966.

INCIDENCE

Thirty-six basaloid carcinomas were identifiedamong 206 cases of squamous cell carcinoma of theanus and anal canal (18 %). If anal margin tumoursare excluded then the incidence rises to 26%. Therewere 17 males and 19 females. The ages of patientsvaried from 41 to 80, the average being 60 years.The mean ages for males and females were notsignificantly different.

SITE OF ORIGIN

Accurate records of the exact location of the tumourswithin the anal canal were available for 33 of the 36cases. In 23 the tumour was located entirely abovethe line of the anal valves (dentate line). Of the other10 cases, six were located mainly above and fourastride the dentate line. No quadrant of the analcanal was particularly affected.

HISTOLOGY

The feature which most distinguishes basaloidcarcinoma from other squamous cell tumours ofthe anal canal is the presence of palisading at theperiphery of the clumps of tumour cells (Figs. 1 and2). The appearance has some resemblance to thepalisading seen in basal cell carcinoma or rodentulcer of the skin. Moreover, a tendency to formsolid, circumscribed clumps of tumour cells con-taining small, round, or ovoid nuclei which areregular in shape and size (Fig. 3) is also reminiscent

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Basaloid carcinoma of the anal canal

of rodent ulcer. Other features suggestive of basal cellcarcinoma include a prominent pseudo-acinarpattern (Fig. 2), which is really a manifestation ofpalisading and was seen in three cases. The formationof concentric whorls of squamoid cells (Figs. 4 and9) in some cases gave the impression of incompletekeratinization. In five cases there were small,sharply defined pearls of keratin scattered in smallnumbers throughout the tumours. In one case thetumour cells showed a patchy tendency to formsmall acini, some of which contained very smallquantities of mucin. In others the clumps of tumourtended to break up to form irregular columns of cells.One feature of the histology unlike basal cell

carcinoma was the presence of a varying amountof eosinophilic necrosis within the clumps cf tumourcells (Fig. 6). This was a prominent feature in 14 ofthe 37 cases. In four of these tumours it was presentin considerable quantity in the middle of the clumpsof tumour, the cells being restricted to a narrowrim around the periphery. It was possible to findwhat appeared to be keratin plugs among the other-wise structureless masses of eosinophilic material.

Other features unlike basal cell carcinoma in-cluded the presence of some variation in the shapeand size of nuclei (Figs. 7 and 8), including giantforms, particularly in those cases regarded as ana-plastic basaloid. The growing edge of our basaloidtumours has shown clear signs of a much greaterdegree of invasiveness than is usually seen in rodentulcer. In a few cases there was a tendency to apapillary growth pattern resembling transitionalcell carcinoma of the bladder.

It must be emphasized that basaloid carcinomasof the anal canal are not a rigidly exclusive group.Their histology is purely or, at least, predominantlybasaloid, but here and there features of squamouscell carcinoma may be present. In our experienceother squamous cell carcinomas of the anal canalmay show occasional small patches of basaloidstructure, but these have not been included in thepresent series of cases. Similarly we have seen a fewanal canal cancers without a basaloid appearancewhich have contained the eosinophilic necrosismentioned above.The 36 tumours were divided into three groups

according to the amount of palisading and theextent to which they retained their capacity to formcircumscribed clumps of cells. Other features suchas the appearance of the nuclei and the amount ofeosinophilic necrosis were also taken into accountin the histological assessment of their malignancy.

GROUP I: WELL-DIFFERENTIATED BASALOID CARCI-NOMA (FIGS. 1-3) There were 10 cases in group I.Palisading was present throughout and the tumour

cells formed circumscribed clumps. The nuclei wereregular in size and shape and mitoses were few. Allcases showed some eosinophilic necrosis but onlyin small amounts.

GROUP II: MODERATELY DIFFERENTIATED BASALOIDCARCINOMA (FIGS. 4 AND 5) There were 12 cases ingroup II. Palisading was patchy and less prominent.Clumping of tumour cells was still present but notquite so circumscribed as in group I. The nucleitended to be larger but were regular in size andshape. The number of mitoses was greater than ingroup I. There was a greater amount of eosinophilicnecrosis than in group I, although it was completelyabsent in one tumour. In another it was extensive.

GROUP m: POORLY DIFFERENTIATED AND ANAPLASTICBASALOID CARCINOMA (FIGS. 6-9) There were 14 casesin group III. Palisading was absent. Clumping oftumour cells was absent in five cases but was presentin the other nine although the clumps were breakingup into irregular columns of cells. The nuclei showedvariation in size and shape, were very hyperchro-matic and there were many mitoses. Eosinophilicnecrosis was a prominent feature in seven of the 14cases, present in small amounts in four cases, andabsent in three tumours. In five cases the appearanceswere particularly anaplastic and resembled the'basaloid small cell' carcinoma of Wittoesch et al.(1957).

It is true that these anaplastic basaloid carcinomashave only a very superficial resemblance to basalcell carcinoma. However, they are distinctive andquite unlike other anaplastic squamous cell tumoursof the anal region.

HISTOGENESIS In some of the pathological speci-mens studied, there has been evidence of the histo-genesis of basaloid carcinomas of the anal canal.Zones of transition between invasive tumour andchanges of a pre-invasive type suggest that basaloidcarcinoma arises from the basal cells of stratifiednon-keratinizing squamous epithelium and from atype which is morphologically intermediate betweenstratified squamous and transitional cell epithelium.

LYMPHATIC SPREAD

Six of the 36 cases received no surgical treatmentbecause of advanced disease, and three were treatedby local excision. One of these had involvement ofinguinal nodes. Of the remaining 27 patients treatedby excision of the rectum and anal region, 14 (52%)had involvement of the regional lymphatic glands.Eight of these had haemorrhoidal nodes only in-volved; four had both haemorrhoidal and inguinal

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Lillian S. C. Pang and B. C. Morson

FIG. 2.

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.. b .4. 1.r:,: *_ '. F .j...

* r

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FIG. 1. Well-dierentiated basaloidcarcinoma. There is palisading ofnucki at the periphery of circum-scribed clumps of tumour cells, thenucki of which are regular in shapeand size. Haematoxylin and eosinx 100.

FIG. 2. Well-differentiated basaloidcarcinoma showing palisading ofnuclei giving a pseudo-acinar pattern.The cells are uniform in shape andsize. Haematoxylin and eosin x 125.

FIG. 3. Well-differentiated basaloidcarcinoma showing solid circum-scribed clumps of tumour cells withsmall round or ovoid nucki whichare regular in shape and size.Haematoxylin and eosin x 100.

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FIG. 4. Moderately differentiatedbasaloid carcinoma. The nuclei areregular in size and shape but thereis only a slight tendency to palisadingof nuclei. The concentric whorls ofsquamous cells in the right-hand sideof the photograph give the impressionof incomplete keratinization.Haematoxylin and eosin x 300.

P FIG. 5. Moderatelydifferentiated basaloidcarcinoma. There is a slight

f tendency to palisading ande the tumour cells are arranged

in solid circumscribed clumps.The nuclei are regular in size

i and shape. Haematoxylinand eosin x 100.

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FIG. 6. Poorly differentiated basaloidcarcinoma. There is extensive eosinophilicnecrosis in the centre of clumps of tumour,the cells being restricted to a narrow rimaround the periphery. Haematoxylin andeosin x 34.

FIG. 7. Poorly differentiatedbasaloid carcinoma. There isclumping of tumour cells butpalisading is absent. Haematoxylinand eosin x 300.

FIG. 8. Poorly differentiatedbasaloid carcinoma. High-power view of:Fig. 7 to showanaplastic features.Haematoxylin and eosin x 425.

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FIG. 9. Anaplastic 'small cell' basaloid carcinoma. Haematoxylin and eosin x 200.

nodes involved; two developed inguinal node in-volvement only.

HISTOLOGY AND LYMPHATIC SPREAD The histologyof the lymph node metastases was generally similarin all cases to the appearance in the primary tumours.The distribution of the three histological grades ofmalignancy among the 14 cases who had lymph-nodemetastases was as follows: four were well differenti-ated, four moderately differentiated, and six ana-plastic basaloids.

RESULTS OF TREATMENT

RADIOTHERAPY Six patients were treated by in-sertion of radium needles or by radiotherapy onlybecause of poor general health or extensive diseasewhich was surgically inoperable. None survived fiveyears. Of four patients with anaplastic basaloidcarcinomas, three were dead from their diseasewithin 18 months and one survived for three years.Two patients had moderately differentiated basaloidtumours; one died one year after treatment and theother survived for nearly three years before dyingof recurrence.

LOCAL EXCISION Three patients were treated bylocal removal of the primary tumour. All had basal-

oid tumours of a moderately differentiated type. Onedied three years after the local excision, which wasconsidered palliative because of involved inguinalglands. A second patient is still alive one year afteroperation followed by radiotherapy. The thirdpatient is alive eight years after local excision for asmall tumour lyingjust above the dentate line.

EXCISION OF RECTUM AND ANAL CANAL Twenty-sevenof the 36 patients in this series were treated byexcision of the rectum and anal region. There werethree post-operative deaths and one patient hasbeen lost to follow-up. Three are still alive and wellless than five years from the time of operationleaving 20 cases available for a study of the relation-ship between pathology and prognosis (Table I).

Eleven of 20 patients (55 %) have survived morethan five years after excision of the rectum, andfive of these lived more than 10 years after operation.All but one of these five had well-differentiatedbasaloid tumours, the other having had a moderatelydifferentiated tumour. Three had lymph nodemetastases in the haemorrhoidal glands of theoperation specimen. Of those nine cases dying beforefive years, eight definitely died of recurrence and oneof a primary carcinoma of the bronchus. Amongthe eight who died of recurrence there were fivewith anaplastic basaloid carcinoma, two with

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TABLE IBASALOID CARCINOMA TREATED BY EXCISION OF RECTUM

WITH ADEQUATE FOLLOW-UP

Lymph Node Metastases Prognosis

Sex Age Haemor- Inguinal Alive (yr.)rhoidal

Group I: well differentiatedM 53 +M 58 +M 71 +F 43 -

F 56 -

F 67 -

F 53 -

M 54 -

M 62 -

- 1012

-i 14

_ 75

_ 5_

5

Group II: moderately differentiatedF 48 + -

F 46 + -

M 45 + -

F 64 - +F 54 - -

1014

Group III: poorly differentiated and anaplasticM 58 + -

M 69 + +M 71 - +M 72 - -

M 63 - -

M 49 - -

Dead (yr.)

11

225

22222

moderately differentiated tumours, and one with awell-differentiated carcinoma. The three patientswith differentiated growths had extensive involve-ment of regional lymphatic glands in the operationspecimen.

LYMPHATIC SPREAD AND PROGNOSIS The prognosisfor patients treated by excision of the rectum withand without lymph node involvement has beencompared. There were 10 patients with involvementof regional glands six of whom had haemorrhoidalnode involvement only; two had both haemorrhoidaland inguinal node involvement and two inguinalgland metastases only. The five-year survival rateof the whole group was four out of 10 cases (40%).The four who survived have all remained alive for10 years since operation. None had inguinal nodemetastasis, whereas all four patients who had in-guinal node involvement died within two years ofoperation. It has previously been shown (Morson,1960) that the inguinal gland direction of spread isan indication of advanced disease that is most un-

likely to be cured by surgical treatment.Among the four patients with lymphatic metas-

tases who survived two had well-differentiatedtumours and two moderately differentiated. Therewere three anaplastic basaloids, two moderatelydifferentiated basaloids, and one well-differentiatedtumour among those six patients who died ofrecurrence. The only patient with well-differentiatedbasaloid who died of recurrence was an advanced

case with both haemorrhoidal and inguinal nodesinvolved at the time of operation.

Seven out of 10 patients without lymph nodemetastases survived five years after excision of therectum (70%). None of these has yet shown anysigns of recurrence and two have now survived formore than 10 years. Six of the seven tumours werewell-differentiated and one moderately differentiated.The three patients who died all had anaplasticbasaloid tumours.

HISTOLOGY AND PROGNOSIS The 20 patients treatedby excision of the rectum who survived operationand for whom accurate follow-up information wasavailable have been subdivided according to thethree grades of malignancy of basaloid carcinomas.The prognosis for these three grades is: for well-differentiated basaloid carcinoma the five-yearsurvival rate is eight out of nine cases (nearly 90%);for the moderately differentiated tumours it wasthree out of five patients (60%); and for the sixundifferentiated (anaplastic) basaloid carcinomasthere were no five-year survivors.

DISCUSSION

Squamous carcinoma of the anal canal is un-common, accounting for only about 3-7% of allcarcinomas of the rectum and anal region. Approxi-mately one in five squamous carcinomas of the analcanal in our material are of the basaloid type whichmakes the latter a relatively rare tumour. Loneet al. (1960) gave an identical frequency for basaloidtumours, but also stated that almost half of all analcancers contain some areas resembling basal cellcarcinoma of the skin. This is a much higherestimate than our studies indicate.

Basaloid tumours characteristically arise from theentodermal-ectodermal junctional zone (cloacogeniczone) of the upper anal canal. This is also thecharacteristic location for the majority of squamouscell carcinomas of the anal region (Morson, 1960).The predilection of basaloid tumours for this zoneis a reflection of its inherent epithelial instability(Walls, 1958) which is a feature of many junctionalzones throughout the body. This explains thevariety of histological growth patterns seen in analcancer. The term 'cloacogenic' has stemmed fromthe work of Herrmann and Desfosses (1880) whoconsidered that the zone is a remnant of the cloaca.In fact it is only one derivative of the cloaca (Tuckerand Hellwig, 1935), no more so than, for example,the urinary bladder. The zone is certainly the site ofthe entodermal-ectodermal junction and it is forthis reason that we prefer the term 'junctional' todescribe it.

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It was not found possible from the study of ourbasaloid cancers to get a complete picture of theirhistogenesis. However, from the material available,it would appear that basaloid carcinomas arise fromproliferation of basal cells of simple non-keratin-izing squamous epithelium. The other types ofepithelium in the junctional zone, stratified columnarand transitional epithelium similar to that found inthe urinary tract, often show squamous metaplasia.Moreover, some of the peculiarities in the histologyof basaloid tumours, such as the formation of smallacini and a tendency to a papillary growth patternresembling transitional cell carcinoma of the bladder,may well be explained by the presence of thesedifferent types of epithelium normally present inthe junctional zone.The concept of basaloid carcinoma of the anal

canal is useful for two main reasons. First, it drawsattention to a histological variant of squamous cellcarcinoma of this region which, excluding theanaplastic basaloids, has a good prognosis. Second-ly, it makes a distinction from true basal cellcarcinoma of the peri-anal skin with which it issometimes confused. It must be emphasized thatbasaloid carcinoma is a potentially metastasizingtumour of the anal canal whereas basal cell carci-noma, in this context, is a non-metastasizingtumour of the hair-bearing skin around the anus.Occasionally, true basal cell carcinomas involve theanal canal by upward spread.The histological feature which most distinguishes

basaloid carcinoma is the presence of palisading ofnuclei at the periphery of the clumps of tumour cells.If this is present then it is indicative of a goodprognosis even though lymphatic metastasis hasalready taken place as judged by examination of theoperation specimen. Lone et al. (1960) noted thatin 'non-lethal' cancers of the anal canal basaloidelements predominated. Thackray (1951) showedthat palisading was a well-marked feature in thoserodent ulcers reacting favourably to radiotherapybut found that only the extent to which growthappeared infiltrative seemed to have a direct bearingon prognosis. In our basaloid tumours of the analcanal the presence of palisading and the relativeabsence of infiltration are likely to be associatedwith a good prognosis.An attempt has been made to grade basaloid

tumours according to the presence or absence ofpalisading and other features, including their

cytological characteristics. The method is justifiedby the results which show that the prognosis is verygood (90% with five-year survival) in cases of well-differentiated basaloid tumours even when lymphaticmetastasis has already occurred. In cases of moder-ately differentiated basaloids the five-year survivalrate of 60% is still considerably better than thesurvival for all squamous cell carcinomas of theanal canal. The anaplastic basaloids, on the otherhand, show an extremely poor prognosis even whenlymphatic metastases are absent. Wittoesch et al.(1957) commented on the poor prognosis of their'small cell' or anaplastic basaloid tumours.The presence of lymphatic metastases has a pro-

found influence on the prognosis of basaloid tumoursas a whole. This is to be expected. If, however, theanaplastic basaloids are excluded then lymph nodeinvolvement has a much less adverse effect onprognosis as evidenced by the fact that four cases ofdifferentiated basaloids with involved lymph nodes(two of group I and two of group II) are still alive10 years after excision of the rectum.Our studies indicate that patients with basaloid

carcinomas of the anal canal should be treated byexcision of the rectum. The one case treated by localexcision which appears to have been cured was asmall tumour with invasion of the submucosaltissues only. This suggests that local excision can bethe treatment of choice provided the tumour issmall, well-differentiated, and accessible to adequatelocal removal.

We wish to thank Dr. A. C. Thackray of the Bland-Sutton Institute of Pathology of the Middlesex Hospitalfor his help; also Mr. Norman Mackie for the photo-graphs and Mr. Lloyd Soodeen for technical assistance.This investigation was supported by grants to Dr.Lillian S. C. Pang from the Medical Research Counciland to Dr. B. C. Morson from the British EmpireCancer Campaign for Research.

REFERENCES

Herrmann, G., and Desfosses, L. (1880). C.R. Acad. Sci. (Paris), 90,1301.

Lone, F., Berg, J. W., and Stearns, M. W., Jr. (1960). Cancer (Philad.),13, 907.

Morson, B. C. (1960). Proc. roy. Soc. Med., 53, 416., and Volkstadt, H. (1963a). J. clin. Path., 16, 200.- (1963b). Ibid., 16, 126.

Thackray, A. C. (1951). Brit. J. Cancer, 5, 213.Tucker, C. C., and Hellwig, C. A. (1935). Arch. Surg., 31, 521.Walls, E. W. (1958). Brit. J. Surg., 45, 504.Wittoesch, J. H., Woolner, L. B., and Jackman, R. J. (1957). Surg.

Gynec. Obstet., 104, 75.

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Basaloid carcinoma ofthe - Journal of Clinical Pathologyjcp.bmj.com/content/jclinpath/20/2/128.full.pdf · true basal cell carcinoma of the peri-anal skin were ... Basaloidcarcinoma