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Epithelioma arising in porokeratosis of Mibelli
British Journal of Plastic Surgery (i 97 z), 25, 31 R-328
EPITHELIOMA ARISING IN P O R O K E R A T O S I S OF MIBELLI
By DAVIDF. CORT, F.R.C.S. Senior Registrar in Plastic Surgery, The Queen Elizabeth Hospital, Birmingham 15
and ABDEL-HAMIDM. ABDEL-Azlz, M.D. 1 Loeum Registrar, Department of Diseases of the Skin, The General Hospital, Birmingham 4 " The trouble with cancer is not that we do not know the cause, but that we know too many causes."
(Prof. H. R. Dean) IN 1893 Mibelli described a curious skin eruption, to which he gave the name Porokeratosis, believing on histological grounds that the fundamental lesion was hyperkeratosis originating at the orifice of a sweat duct. The condition is now classified as a chronic progressive kerato-atrophoderma, and has until recently been regarded as a benign entity, notable for its rarity and failure to respond to treatment. T w o patients presenting with epitheliomato~as degeneration in areas of Porokeratosis prompted further enquiry, and a search of the literature revealed 13 previously recorded cases. These have been reviewed, and consideration is given to the place of surgery in the management of Porokeratosis and its neoplastic complications.
CLINICAL Porokeratosis is a familialconditionwith male predominance,occasionallyoccurring sporadically. Onset is usually in childhood, and the skin eruption tends to progress throughout life. There are no known systemicnor metabolicconcomitants,and spontaneous remission is exceptional. The classic skin lesion (Fig. I) is circular or irregular, and varies from 2 ram. to about 2o mm. in diameter, consisting of a peripheral pigmented zone of hyperkeratosis and a central region of atrophy. The periphery of the lesion is slightly raised above the surrounding surface, and feels rough to the palpating finger. The lesions tend to be confluent, and occur mainly on the distal parts of the limbs. They may affect the trunk and genitalia, and less commonly appear on the face. Involvement of the mucous membrane of the mouth, and of the nails, is recognised. In many cases the condition is limited strictly to one side of the body, and the significance of this distribution is unknown. Lesions may form curious linear patterns on the limbs (Fig. 2), not conforming to any anatomical entity. The skin eruption is usually asymptomatic, although irritation has been reported in children, and the appearance tends to be less florid in cold weather. The clinical picture is known to vary in respect of the extent, prominence and pigmentation of the lesions (Mikhail and Wertheim, 1968), and a lesser variant condition dependent upon actinic activation is recognised (Chernosky, 1967). Three forms of pattern of distribution of the lesions are defined in the mature (adult) case : I. Unilateral involvement of the trunk and limbs. 2. Localised to a single limb. 3. Generalised, usually upon all limbs, with or without involvement of trunk and face. x At present lecturer in Dermatologyand Venereology~A1-Azhar University, Cairo, U.A.R° arR
EPITHELIOMA
A R I S I N G IN P O R O K E R A T O S I S OF M I B E L L I
319
The occurrence of Porokeratosis in negroes (E1-Mofty, I956 ; Seif-E1-Nasr, I962 ) and orientals (Hall, I928) has been recorded, but the small numbers of case reports preclude any comment upon racial preponderance. The extent of body surface involve d ment varies from I per cent to about 3° per cent, and the rate of extension of the eruption is extremely variable, but tends to become slower with advancing age.
F~G. 2.
FIG. I FIG. 2 FIG. I. Typical Porokeratosis lesions on the buttock of Case I. Curious linear distribution of lesions on the lower limb of Case I. Note the ulcerated area on the medial aspect of the knee, in which malignant change has taken place.
Clinical diagnosis of the condition is essentially dependent upon awareness of its existence, and histological examination of an adequate biopsy is mandatory. It is apparent that a number of cases (including our own) have been labelled as psoriasis or ichythosis hystrix, and there was a superficial resemblance to both of these conditions (Savage and Lederer, I95I). HISTOLOGY
Diagnosis rests upon demonstration of the cornoid lamella, a horny plug situated in a deep groove in the centre of the keratotic margin of the lesion. Immediately beneath the cornoid lamella, the granular layer is absent (Lever, i967). The essential features of the histology are shown in Figs. 3 and 4. Mibelti's original histological interpretation no longer holds credence (Mikhail and Wertheim, x968), hence the term " Porokeratosis " is actually a misnomer. In a recent
320
BRITISH JOURNAL OF PLASTIC SURGERY
critical review (Reed and Leone, I97o) the precise nature of the condition has been defined as a mutant clonal keratosis of the epidermis, and these authors predict a precancerous potentiality.
FIG. 3. Photomicrograph showing the Cornoid lamella from a lesion in Case I. TREATMENT
Attempts to treat the disease have met with a singular lack of success. Keratolytics, thyroid extract, Vitamin A and topical steroids have all been advocated, without significant effect. Irradiation has been tried in a number of cases, as in other intractable conditions of the skin, but again no lasting benefit has resulted. With a clearer understanding of the nature of the epidermal abnormality, the possibility of irradiation acting as a co-factor in carcinogenesis deserves serious consideration. For this reason, radiotherapy should no longer find an application in the treatment of Porokeratosis (Banks, I97I). Surgery has received scant attention as a therapeutic approach, possibly on account
EPITHELIOMA
A R I S I N G iN P O R O K E R A T O S I S OF M I B E L L I
32 I
o f the essentially symptomless nature o f the disease, and the extent o f skin resection which would be required in some cases. Excision and grafting o f extensive areas o f afflicted skin for an apparently harmless condition would clearly appeal to neither patient nor dermatologist. Jones and Smith (1947) state that excision is the only effective treatment, without elaborating upon the subject. Rook et al. (1968) comment that small lesions may be excised, but tend to recur. No reference to any series o f cases treated by surgical methods has been found.
FIG. 4.
P h o t o m i c r o g r a p h showing the central atrophic area from a lesion in Case I.
CAS~ REVORTS Case I. A Caucasian male developed a skin eruption on the left lower limb at the age of 2. There were no symptoms, and there was no family history of skin disease. Over the next ten years the lesions extended to involve the entire limb, buttock, lower abdomen and loin, and in early adult life the upper arm became involved, but the process remained strictly localised to the left side of the body. Various topical medications, including steroids, were ineffective. At the age of 22 a diagnosis of ichthyosis hystrix was made, and the leg was treated with three applications of Thorium X. One year later he received 4 exposures to 300 r, again restricted to the leg. No effect was detected, and no further treatment sought. At the age of 35, small ulcerated lesions appeared on the medial side of the knee, over the tendo Achillis, and on the front of the ankle. These persisted and slowly enlarged, and at 37 he was again referred to the Dermatology clinic. A clinical diagnosis of Porokeratosis of Mibelli was made, with epitheliomatous degeneration at the sites of the ulcers (Dr E. A. Fairburn). Both diagnoses were confirmed on biopsy, and the patient was referred for plastic
FIG. 5, Malignant ulcer over the tendo Achillis in Case I.
FIG. 6.
Photomicrograph to show epitheliomatous change in the ankle lesion of Case I.
EPITHELIOMA ARISING IN POROKERATOSIS OF MIBELLI
323
Lrgery in respect of the turnouts (Figs. 2 and 5). Apart from the frankly malignant areas, it as noted that lesions on the lower limb (i.e. in the zone previously exposed to irradiation) )peared to be in a more active phase than those on other parts of the body. There was no .,gional lymphadenopathy, and general physical examination, blood count, and biochemical rofile were unremarkable; the chest X-ray was clear. At operation the epitheliomata were widely excised with preservation of deep fascia, and le defects closed with thick split skin grafts taken from the contralateral buttock and loin. [ealing was uneventful, with ioo per cent take of the grafts. Histological examination con°. rmed the nature of the three epitheliomata (Fig. 6), indicating adequate clearance of the lmours by the plane of excision.
FIG. 7. Photomicrograph showing carcinoma in situ in a previously irradiated area on the thigh of Case I. Previous irradiation is believed to have predisposed to malignant change in this case. In view of the age of the patient and the unstable appearance of the lower limb skin, further biopsies were taken from the thigh, and these showed evidence of carcinoma in situ (Fig. 7). Excision of the affected skin of the limb, and resurfacing with grafts from the contra-lateral side of the body, is therefore proposed, in the form of a series of staged procedures. Case 2. A Caucasian female developed an asymptomatic eruption on both lower limbs at the age of 2, and over the next fifteen years this steadily extended to involve both upper and lower limbs. The face and trunk were spared, and there was no family history of skin disease. Within the confines of the limbs~ the eruption became more widespread and florid following her only pregnancy at the age of 3o. There was a marked tendency to remission during cold weather. Topical medications were ineffective, and no irradiation was used.
324
BRITISH JOURNAL OF PLASTIC SURGERY
At 43 she developed an epithelioma in the left gluteal fold, which was treated by excision and grafting. The split skin grafts were taken from apparently normal skin on the posterior surface of the opposite thigh. At that time a policy of prophylactic regional lymph node excision was followed (I954), and although no nodes were palpable a left groin block dissection was performed several weeks after the initial procedure. The nodes were found to be free from tumour, and the nature of the original skin abnormality was not identified. At 49, two further epitheliomata were excised from the lateral aspect of the left lower leg, and the defects dosed by grafting. Over the next nine years further lesions appeared on the upper limbs, and those on the legs became more florid. The continued presence of a wide-
FIG. 8. Photomicrograph showing noeplastic change in a lesion on the left leg in Case 2. spread eruption with episodes of malignant transformation led to further investigation, and in 1968 a series of biopsies revealed the diagnosis of Porokeratosis of Mibelli. At 59 (in 197o) she developed small epitheliomata on the right forearm and left lower leg (Fig. 8). These were excised, the former wound closed by direct suture and the latter requiring a split skin graft. Three months later a suspicious area was noted on the medial surface of the right knee. On this occasion the patient was not inclined to accept surgery, and the lesion was treated by radiotherapy, which caused effective regression (Fig. 9). She has recently been assessed in respect of further surgery, since the appearance of the anterior surface of both lower legs is suggestive of w.ide-spread potential malignancy (Fig. IO). In view of her age and the extent of the diseased skin, excision and resurfacing with grafts is not considered a practicable proposition. A policy of frequent review with irradiation for unstable lesions has been accepted. There is as yet no evidence of metastases in this case.
EPITHELIOMA ARISING IN POROKERATOSIS OF MIBELL•
325
It is of interest that several small Porokeratotic lesions are present near the centre of the kin graft on the left gluteal region, 17 years after operation. Their duration is not known~ nd their presence is believed due to the fact that the donor site has been shown in retrospect to ~e a potentially diseased area.
FiG. i o POROKERATOSIS AND CANCER A summary of the available facts in respect of previously reported cases of neoplastic degeneration in Porokeratosis in presented in Table I, and our own cases are included. The first published report is that of Vigne (I942), almost half a century after MibeUi's original article. No major review of Porokeratosis gives any consideration to malignant change until that of Bazex and Dupre in I968, and there are only two previous reports in the British literature (Johnston, I958 ; Savage, I964). Cases I and 2 are quoted by Bazex and Dupre from Kaufmann's thesis (I958), and Case 4 is annotated briefly by Johnston. From the histories of our cases and a review of the literature, it is clear that the diagnosis of Porokeratosis has frequently been delayed for many years. This is attributed to the rarity of the disease, lack of acquaintance with the histological features, and failure of pursuit of a diagnosis in respect of an asymptomatic condition. In only one instance (Savage, I964) has malignant change been observed to occur in a known case, and in the remainder a correct diagnosis was not established until treatment was sought for neoplastic complications. The malignant lesion took the form of" squamous cell carcinoma in 14 cases, with one basal cell carcinoma and three instances of associated Bowen's disease. The tumours in both of our cases were multifocal, and appeared to have arisen in the atrophic zone of the Porokeratotic lesion. We are not aware of any previous report of this latter observation. All turnouts (except the single genital case) were sited upon the limbs,
326
B R I T I S H J O U R N A L OF P L A S T I C SURGERY
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EPITHELIOMA ARISING IN POROKERATOSIS OF MIBELLI
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with a predilection for more distal areas, and this suggests that repeated minor trauma may be implicated in the liability to malignant change. The significance of previous irradiation has already been mentioned, and in four cases therc is definite evidence of such exposure. In three of these the interval between irradiation therapy and subsequent development of malignancy is of the order of 15 years, and it is reasonable to assume a direct relationship between these events (Banks, 1971). Bazex and Dupre were impressed by the similarity in appearance between arsenical cancer of the skin as seen in vineyard workers and the lesions in their patients with Porokeratosis cancer. Since arsenic compounds have been used extensively in the treatment of cutaneous disease, they made careful enquiry in respect of occupational exposure to arsenic and the use of arsenical medications, with negative results. These factors were readily excluded in our cases. Although Porokeratosis is usually stated to be a familial condition, a positive family history is recorded in only two of the fifteen cases ; thus it would appear that the risk of malignancy is greater in sporadic than in familial cases. The total number of recorded cases is of the order of 2o0 (Butterworth and Stream, I96X), and 15 instances of malignant change give in incidence of 7"5 per cent. The true significance of these figures is difficult to assess. It is our impression that the disease is less rare than is suggested by published reports, and that in fact the true rarity is that of a correct diagnosis. The malignant lesions in both of our cases were not aggressively invasive. In Case I, all tumours were cleared by a plane of excision sparing the deep fascia, despite paucity of subcutaneous tissue at two sites. Case 2 has survived excision of five epitheliomata over 17 years, with no evidence of local recurrence nor metastases. We have found no reference to the appearance of metastases in the cases reviewed, and the prognosis of adequately treated Porokeratosis cancer would appear to be favourable. MANAGEMENT OF POROKERATOSIS Recognition of the premalignant nature of Porokeratosis leads to consideration of appropriate management. Neoplastic change may occur as early as the third decade, and it is clear that regular supervision throughout life is required. Annual review is recommended, in order to maintain accurate observation of the progress of the disease and to provide an opportunity for biopsy of any suspicious lesion. Histological confirmation of malignant change will indicate the need for surgery appropriate to the nature of the turnout, and in most cases this will follow the accepted principles of treatment for epithelioma. Prophylactic excision of premalignant lesions is theoretically desirable, but general application of this policy in Porokeratosis is probably not justified. From the findings in this review, two types of case are noted to carry a high risk of malignant change, lesions previously exposed to therapeutic irradiation and lesions sited upon the extremities. Prophylactic excision of Porokeratosis within these categories is worthy of careful consideration, provided that surgical intervention is a practicable proposition in terms of the extent of ablation required and the overall status of the patient. Donor site selection in this condition should take account of the progressive nature of the disease, since it is clearly desirable to avoid the use of potentially involved areas. The skin of the trunk is frequently spared, and as a general principle there is considerable advantage in using the trunk as a donor ske in preference to the limbs (Cort and Herbert, 1971). In the case of unilateral disease, grafts must be taken from the contralateral side of the body, and the lower limb may then also be needed as a donor site.
328
B R I T I S H JOURNAL OF PLASTIC SURGERY SUMMARY
Two cases of multiple squamous cell carcinomata arising in areas of Porokeratosis of Mibelli are reported, and I 3 previous cases are reviewed. Attention is drawn to the premalignant nature of Porokeratosis, and to the danger of irradiation therapy in this condition. The concept of regular adequate observation is discussed, and indications for surgical intervention are suggested. We wish to thank Dr E. A. Fairburn, who established the diagnosis in both cases, and M r O. To Mansfield, under whose care the surgical treatment of Case I was undertaken, for their encouragement in the preparation of this report M r A. Gourevitch and M r T. G. Watts have both kindly assented to publication of details of their surgical treatment of Case 2, as has Dr G. A. Newsholme in respect of recent irradiation in this case. We are indebted to Professor D. B. Brewer for advice upon histopathology, and to M r T. Dee and M r G. R. Cooper for the photographs. We also wish to thank M r R. H. Cort and Dr T. L. Goodfellow for providing translations of the Continental papers reviewed. REFERENCES BANKS, A. J. (1971). Personal communication. BAZEX, A. and DUPRE, A. (1968). Porok6ratose de Mibelli Zoniforme avec d~g6n6rescence. Annales de Dermatologie et de Syphiligraphie Paris, 95, 361-374. BEORE¥, J., ROUSSELOT, R. and WOLFOWCZ, G. (1960). Porokdratose de Mibelli. Transformation epitheliomsteuse. Bulletin de la Socidtd Fran~aise de Dermatologie et de Syphiligraphie, 68, 653. BUTTERWORTH, T. and STREAM, L. B. (1962). ~' Clinical Genodermatology ", p. 26. Baltimore : Williams and Wilkins. CHERNOSKY, M. E. and FREEMAN, R. G. (1967). Disseminated superficial actinic porokera• tosis. Archives of Dermatology, 96, 611-624. CIULA, V. (1968). Epithelioma spinocellulare insorto su porocheratosi del Mibelli. Minerva Dermatologica, 41, 354-357CORT, D. F. and HERBERT, n . C. (1971). Practical aspects of skin grafting. British Journal of Hospital Medicine, 5, 462-471. EL MOFTY, A. M. (1956). Porokeratosis of Mibelli. Journal of the Egyptian Medical Association, 39, 314-318. GANDOLA, M. (1951). La Porocheratosi di Mibelli. Aspetti evolutivi tardivi e associazioni morbose insolite. Bollettino Societa Medicina Chirurgia Pavia~ 65, 275-292. HALL, G. A. M. (1928). Porokeratosis (Mibelli). Report of its occurrence in six Chinese patients. Archives of Dermatology and Syphilology, 18, 396-414 . JOHNSTON, E. N. M. (1958). Porokeratosis of Mibelli with squamous cell carcinoma. British Journal of Dermatology, 70, 351. JONES, P. E. and SMITH, D. C. (I947)- Porokeratosis. Review and report of cases. Archives of Dermatology and Syphilology, 56, 425-436. • KAUFMANN,P. (I958). " Porok6ratose de Mibelli." Paris : These. LEVER, W. F. (I967). " Histopathology of the Skin ", 4th Edition, pp. 62-63. Philadelphia : Lippincott. LOMBARDO, C. (I9O7). Cited by Kaufmann. LOVELL, S. (I945). Cited by Kaufmann. MmELLI V. (1893). Contributo allo studio della ipercheratosi dei canalo sudoriferi. Giornale Italiano Malattia Venero, 28, 313-355 . MIKHAtL, G. R. and WERTHEIM, F. W. (I968). Clinical variants of Porokeratosis (Mibelli). Archives of Dermatology, 98, IZ4-I3I. OBERSTE-LEHN, H. and MOLL, B. (1968). Porokeratosis Mibelli n n d StachelzeUcarcinom. Hautarzt, 19, 399-403 . REED, R . J . andLEoNE, P. (197o). Porokeratosis--amutant clonalkeratosisoftheepidermis. Archives of Dermatology, i o i , 34o-347 . ROBIN, H. H. (1953). Porokeratosis (Mibelli). Archives of Dermatology, 67, 526-527 • ROOK, A., WILKINSON, D. S. and EBLING, F. J. G. (I968). " Textbook of Dermatology ", Vol. 2, pp. lO62-1o63. Oxford. Blackwetl. SAVAGE, J. (1964). Porokeratosis (Mibelli) and carcinoma. British Journal of Dermatology, 76, 489. SAVAGE, J. and LEDERER, H. (1951). Porokeratosis (Mibelli). A case with extensive lesions. Results of animal inoculation. British Journal of Dermatology, 63, 187-192SEIF-EL-NASR, H., ALV, A. M. and ROAYA, F. (1962). Porokeratosis of Mibelli. Journal of the Egyptian Medical Association 45, 181-188. SMITH, P. (I95O). Cited by Johnston. VIGNE, P. (1942). Porok6ratose de MibeUi. Trois cas familiaux. Transformation n6oplasique chez l'un d'eux. Annales de Dermatologie et de Syphiligraphie, Paris, 2, 5-15.
EPITHELIOMA ARISING IN P O R O K E R A T O S I S OF MIBELLI
By DAVIDF. CORT, F.R.C.S. Senior Registrar in Plastic Surgery, The Queen Elizabeth Hospital, Birmingham 15
and ABDEL-HAMIDM. ABDEL-Azlz, M.D. 1 Loeum Registrar, Department of Diseases of the Skin, The General Hospital, Birmingham 4 " The trouble with cancer is not that we do not know the cause, but that we know too many causes."
(Prof. H. R. Dean) IN 1893 Mibelli described a curious skin eruption, to which he gave the name Porokeratosis, believing on histological grounds that the fundamental lesion was hyperkeratosis originating at the orifice of a sweat duct. The condition is now classified as a chronic progressive kerato-atrophoderma, and has until recently been regarded as a benign entity, notable for its rarity and failure to respond to treatment. T w o patients presenting with epitheliomato~as degeneration in areas of Porokeratosis prompted further enquiry, and a search of the literature revealed 13 previously recorded cases. These have been reviewed, and consideration is given to the place of surgery in the management of Porokeratosis and its neoplastic complications.
CLINICAL Porokeratosis is a familialconditionwith male predominance,occasionallyoccurring sporadically. Onset is usually in childhood, and the skin eruption tends to progress throughout life. There are no known systemicnor metabolicconcomitants,and spontaneous remission is exceptional. The classic skin lesion (Fig. I) is circular or irregular, and varies from 2 ram. to about 2o mm. in diameter, consisting of a peripheral pigmented zone of hyperkeratosis and a central region of atrophy. The periphery of the lesion is slightly raised above the surrounding surface, and feels rough to the palpating finger. The lesions tend to be confluent, and occur mainly on the distal parts of the limbs. They may affect the trunk and genitalia, and less commonly appear on the face. Involvement of the mucous membrane of the mouth, and of the nails, is recognised. In many cases the condition is limited strictly to one side of the body, and the significance of this distribution is unknown. Lesions may form curious linear patterns on the limbs (Fig. 2), not conforming to any anatomical entity. The skin eruption is usually asymptomatic, although irritation has been reported in children, and the appearance tends to be less florid in cold weather. The clinical picture is known to vary in respect of the extent, prominence and pigmentation of the lesions (Mikhail and Wertheim, 1968), and a lesser variant condition dependent upon actinic activation is recognised (Chernosky, 1967). Three forms of pattern of distribution of the lesions are defined in the mature (adult) case : I. Unilateral involvement of the trunk and limbs. 2. Localised to a single limb. 3. Generalised, usually upon all limbs, with or without involvement of trunk and face. x At present lecturer in Dermatologyand Venereology~A1-Azhar University, Cairo, U.A.R° arR
EPITHELIOMA
A R I S I N G IN P O R O K E R A T O S I S OF M I B E L L I
319
The occurrence of Porokeratosis in negroes (E1-Mofty, I956 ; Seif-E1-Nasr, I962 ) and orientals (Hall, I928) has been recorded, but the small numbers of case reports preclude any comment upon racial preponderance. The extent of body surface involve d ment varies from I per cent to about 3° per cent, and the rate of extension of the eruption is extremely variable, but tends to become slower with advancing age.
F~G. 2.
FIG. I FIG. 2 FIG. I. Typical Porokeratosis lesions on the buttock of Case I. Curious linear distribution of lesions on the lower limb of Case I. Note the ulcerated area on the medial aspect of the knee, in which malignant change has taken place.
Clinical diagnosis of the condition is essentially dependent upon awareness of its existence, and histological examination of an adequate biopsy is mandatory. It is apparent that a number of cases (including our own) have been labelled as psoriasis or ichythosis hystrix, and there was a superficial resemblance to both of these conditions (Savage and Lederer, I95I). HISTOLOGY
Diagnosis rests upon demonstration of the cornoid lamella, a horny plug situated in a deep groove in the centre of the keratotic margin of the lesion. Immediately beneath the cornoid lamella, the granular layer is absent (Lever, i967). The essential features of the histology are shown in Figs. 3 and 4. Mibelti's original histological interpretation no longer holds credence (Mikhail and Wertheim, x968), hence the term " Porokeratosis " is actually a misnomer. In a recent
320
BRITISH JOURNAL OF PLASTIC SURGERY
critical review (Reed and Leone, I97o) the precise nature of the condition has been defined as a mutant clonal keratosis of the epidermis, and these authors predict a precancerous potentiality.
FIG. 3. Photomicrograph showing the Cornoid lamella from a lesion in Case I. TREATMENT
Attempts to treat the disease have met with a singular lack of success. Keratolytics, thyroid extract, Vitamin A and topical steroids have all been advocated, without significant effect. Irradiation has been tried in a number of cases, as in other intractable conditions of the skin, but again no lasting benefit has resulted. With a clearer understanding of the nature of the epidermal abnormality, the possibility of irradiation acting as a co-factor in carcinogenesis deserves serious consideration. For this reason, radiotherapy should no longer find an application in the treatment of Porokeratosis (Banks, I97I). Surgery has received scant attention as a therapeutic approach, possibly on account
EPITHELIOMA
A R I S I N G iN P O R O K E R A T O S I S OF M I B E L L I
32 I
o f the essentially symptomless nature o f the disease, and the extent o f skin resection which would be required in some cases. Excision and grafting o f extensive areas o f afflicted skin for an apparently harmless condition would clearly appeal to neither patient nor dermatologist. Jones and Smith (1947) state that excision is the only effective treatment, without elaborating upon the subject. Rook et al. (1968) comment that small lesions may be excised, but tend to recur. No reference to any series o f cases treated by surgical methods has been found.
FIG. 4.
P h o t o m i c r o g r a p h showing the central atrophic area from a lesion in Case I.
CAS~ REVORTS Case I. A Caucasian male developed a skin eruption on the left lower limb at the age of 2. There were no symptoms, and there was no family history of skin disease. Over the next ten years the lesions extended to involve the entire limb, buttock, lower abdomen and loin, and in early adult life the upper arm became involved, but the process remained strictly localised to the left side of the body. Various topical medications, including steroids, were ineffective. At the age of 22 a diagnosis of ichthyosis hystrix was made, and the leg was treated with three applications of Thorium X. One year later he received 4 exposures to 300 r, again restricted to the leg. No effect was detected, and no further treatment sought. At the age of 35, small ulcerated lesions appeared on the medial side of the knee, over the tendo Achillis, and on the front of the ankle. These persisted and slowly enlarged, and at 37 he was again referred to the Dermatology clinic. A clinical diagnosis of Porokeratosis of Mibelli was made, with epitheliomatous degeneration at the sites of the ulcers (Dr E. A. Fairburn). Both diagnoses were confirmed on biopsy, and the patient was referred for plastic
FIG. 5, Malignant ulcer over the tendo Achillis in Case I.
FIG. 6.
Photomicrograph to show epitheliomatous change in the ankle lesion of Case I.
EPITHELIOMA ARISING IN POROKERATOSIS OF MIBELLI
323
Lrgery in respect of the turnouts (Figs. 2 and 5). Apart from the frankly malignant areas, it as noted that lesions on the lower limb (i.e. in the zone previously exposed to irradiation) )peared to be in a more active phase than those on other parts of the body. There was no .,gional lymphadenopathy, and general physical examination, blood count, and biochemical rofile were unremarkable; the chest X-ray was clear. At operation the epitheliomata were widely excised with preservation of deep fascia, and le defects closed with thick split skin grafts taken from the contralateral buttock and loin. [ealing was uneventful, with ioo per cent take of the grafts. Histological examination con°. rmed the nature of the three epitheliomata (Fig. 6), indicating adequate clearance of the lmours by the plane of excision.
FIG. 7. Photomicrograph showing carcinoma in situ in a previously irradiated area on the thigh of Case I. Previous irradiation is believed to have predisposed to malignant change in this case. In view of the age of the patient and the unstable appearance of the lower limb skin, further biopsies were taken from the thigh, and these showed evidence of carcinoma in situ (Fig. 7). Excision of the affected skin of the limb, and resurfacing with grafts from the contra-lateral side of the body, is therefore proposed, in the form of a series of staged procedures. Case 2. A Caucasian female developed an asymptomatic eruption on both lower limbs at the age of 2, and over the next fifteen years this steadily extended to involve both upper and lower limbs. The face and trunk were spared, and there was no family history of skin disease. Within the confines of the limbs~ the eruption became more widespread and florid following her only pregnancy at the age of 3o. There was a marked tendency to remission during cold weather. Topical medications were ineffective, and no irradiation was used.
324
BRITISH JOURNAL OF PLASTIC SURGERY
At 43 she developed an epithelioma in the left gluteal fold, which was treated by excision and grafting. The split skin grafts were taken from apparently normal skin on the posterior surface of the opposite thigh. At that time a policy of prophylactic regional lymph node excision was followed (I954), and although no nodes were palpable a left groin block dissection was performed several weeks after the initial procedure. The nodes were found to be free from tumour, and the nature of the original skin abnormality was not identified. At 49, two further epitheliomata were excised from the lateral aspect of the left lower leg, and the defects dosed by grafting. Over the next nine years further lesions appeared on the upper limbs, and those on the legs became more florid. The continued presence of a wide-
FIG. 8. Photomicrograph showing noeplastic change in a lesion on the left leg in Case 2. spread eruption with episodes of malignant transformation led to further investigation, and in 1968 a series of biopsies revealed the diagnosis of Porokeratosis of Mibelli. At 59 (in 197o) she developed small epitheliomata on the right forearm and left lower leg (Fig. 8). These were excised, the former wound closed by direct suture and the latter requiring a split skin graft. Three months later a suspicious area was noted on the medial surface of the right knee. On this occasion the patient was not inclined to accept surgery, and the lesion was treated by radiotherapy, which caused effective regression (Fig. 9). She has recently been assessed in respect of further surgery, since the appearance of the anterior surface of both lower legs is suggestive of w.ide-spread potential malignancy (Fig. IO). In view of her age and the extent of the diseased skin, excision and resurfacing with grafts is not considered a practicable proposition. A policy of frequent review with irradiation for unstable lesions has been accepted. There is as yet no evidence of metastases in this case.
EPITHELIOMA ARISING IN POROKERATOSIS OF MIBELL•
325
It is of interest that several small Porokeratotic lesions are present near the centre of the kin graft on the left gluteal region, 17 years after operation. Their duration is not known~ nd their presence is believed due to the fact that the donor site has been shown in retrospect to ~e a potentially diseased area.
FiG. i o POROKERATOSIS AND CANCER A summary of the available facts in respect of previously reported cases of neoplastic degeneration in Porokeratosis in presented in Table I, and our own cases are included. The first published report is that of Vigne (I942), almost half a century after MibeUi's original article. No major review of Porokeratosis gives any consideration to malignant change until that of Bazex and Dupre in I968, and there are only two previous reports in the British literature (Johnston, I958 ; Savage, I964). Cases I and 2 are quoted by Bazex and Dupre from Kaufmann's thesis (I958), and Case 4 is annotated briefly by Johnston. From the histories of our cases and a review of the literature, it is clear that the diagnosis of Porokeratosis has frequently been delayed for many years. This is attributed to the rarity of the disease, lack of acquaintance with the histological features, and failure of pursuit of a diagnosis in respect of an asymptomatic condition. In only one instance (Savage, I964) has malignant change been observed to occur in a known case, and in the remainder a correct diagnosis was not established until treatment was sought for neoplastic complications. The malignant lesion took the form of" squamous cell carcinoma in 14 cases, with one basal cell carcinoma and three instances of associated Bowen's disease. The tumours in both of our cases were multifocal, and appeared to have arisen in the atrophic zone of the Porokeratotic lesion. We are not aware of any previous report of this latter observation. All turnouts (except the single genital case) were sited upon the limbs,
326
B R I T I S H J O U R N A L OF P L A S T I C SURGERY
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with a predilection for more distal areas, and this suggests that repeated minor trauma may be implicated in the liability to malignant change. The significance of previous irradiation has already been mentioned, and in four cases therc is definite evidence of such exposure. In three of these the interval between irradiation therapy and subsequent development of malignancy is of the order of 15 years, and it is reasonable to assume a direct relationship between these events (Banks, 1971). Bazex and Dupre were impressed by the similarity in appearance between arsenical cancer of the skin as seen in vineyard workers and the lesions in their patients with Porokeratosis cancer. Since arsenic compounds have been used extensively in the treatment of cutaneous disease, they made careful enquiry in respect of occupational exposure to arsenic and the use of arsenical medications, with negative results. These factors were readily excluded in our cases. Although Porokeratosis is usually stated to be a familial condition, a positive family history is recorded in only two of the fifteen cases ; thus it would appear that the risk of malignancy is greater in sporadic than in familial cases. The total number of recorded cases is of the order of 2o0 (Butterworth and Stream, I96X), and 15 instances of malignant change give in incidence of 7"5 per cent. The true significance of these figures is difficult to assess. It is our impression that the disease is less rare than is suggested by published reports, and that in fact the true rarity is that of a correct diagnosis. The malignant lesions in both of our cases were not aggressively invasive. In Case I, all tumours were cleared by a plane of excision sparing the deep fascia, despite paucity of subcutaneous tissue at two sites. Case 2 has survived excision of five epitheliomata over 17 years, with no evidence of local recurrence nor metastases. We have found no reference to the appearance of metastases in the cases reviewed, and the prognosis of adequately treated Porokeratosis cancer would appear to be favourable. MANAGEMENT OF POROKERATOSIS Recognition of the premalignant nature of Porokeratosis leads to consideration of appropriate management. Neoplastic change may occur as early as the third decade, and it is clear that regular supervision throughout life is required. Annual review is recommended, in order to maintain accurate observation of the progress of the disease and to provide an opportunity for biopsy of any suspicious lesion. Histological confirmation of malignant change will indicate the need for surgery appropriate to the nature of the turnout, and in most cases this will follow the accepted principles of treatment for epithelioma. Prophylactic excision of premalignant lesions is theoretically desirable, but general application of this policy in Porokeratosis is probably not justified. From the findings in this review, two types of case are noted to carry a high risk of malignant change, lesions previously exposed to therapeutic irradiation and lesions sited upon the extremities. Prophylactic excision of Porokeratosis within these categories is worthy of careful consideration, provided that surgical intervention is a practicable proposition in terms of the extent of ablation required and the overall status of the patient. Donor site selection in this condition should take account of the progressive nature of the disease, since it is clearly desirable to avoid the use of potentially involved areas. The skin of the trunk is frequently spared, and as a general principle there is considerable advantage in using the trunk as a donor ske in preference to the limbs (Cort and Herbert, 1971). In the case of unilateral disease, grafts must be taken from the contralateral side of the body, and the lower limb may then also be needed as a donor site.
328
B R I T I S H JOURNAL OF PLASTIC SURGERY SUMMARY
Two cases of multiple squamous cell carcinomata arising in areas of Porokeratosis of Mibelli are reported, and I 3 previous cases are reviewed. Attention is drawn to the premalignant nature of Porokeratosis, and to the danger of irradiation therapy in this condition. The concept of regular adequate observation is discussed, and indications for surgical intervention are suggested. We wish to thank Dr E. A. Fairburn, who established the diagnosis in both cases, and M r O. To Mansfield, under whose care the surgical treatment of Case I was undertaken, for their encouragement in the preparation of this report M r A. Gourevitch and M r T. G. Watts have both kindly assented to publication of details of their surgical treatment of Case 2, as has Dr G. A. Newsholme in respect of recent irradiation in this case. We are indebted to Professor D. B. Brewer for advice upon histopathology, and to M r T. Dee and M r G. R. Cooper for the photographs. We also wish to thank M r R. H. Cort and Dr T. L. Goodfellow for providing translations of the Continental papers reviewed. REFERENCES BANKS, A. J. (1971). Personal communication. BAZEX, A. and DUPRE, A. (1968). Porok6ratose de Mibelli Zoniforme avec d~g6n6rescence. Annales de Dermatologie et de Syphiligraphie Paris, 95, 361-374. BEORE¥, J., ROUSSELOT, R. and WOLFOWCZ, G. (1960). Porokdratose de Mibelli. Transformation epitheliomsteuse. Bulletin de la Socidtd Fran~aise de Dermatologie et de Syphiligraphie, 68, 653. BUTTERWORTH, T. and STREAM, L. B. (1962). ~' Clinical Genodermatology ", p. 26. Baltimore : Williams and Wilkins. CHERNOSKY, M. E. and FREEMAN, R. G. (1967). Disseminated superficial actinic porokera• tosis. Archives of Dermatology, 96, 611-624. CIULA, V. (1968). Epithelioma spinocellulare insorto su porocheratosi del Mibelli. Minerva Dermatologica, 41, 354-357CORT, D. F. and HERBERT, n . C. (1971). Practical aspects of skin grafting. British Journal of Hospital Medicine, 5, 462-471. EL MOFTY, A. M. (1956). Porokeratosis of Mibelli. Journal of the Egyptian Medical Association, 39, 314-318. GANDOLA, M. (1951). La Porocheratosi di Mibelli. Aspetti evolutivi tardivi e associazioni morbose insolite. Bollettino Societa Medicina Chirurgia Pavia~ 65, 275-292. HALL, G. A. M. (1928). Porokeratosis (Mibelli). Report of its occurrence in six Chinese patients. Archives of Dermatology and Syphilology, 18, 396-414 . JOHNSTON, E. N. M. (1958). Porokeratosis of Mibelli with squamous cell carcinoma. British Journal of Dermatology, 70, 351. JONES, P. E. and SMITH, D. C. (I947)- Porokeratosis. Review and report of cases. Archives of Dermatology and Syphilology, 56, 425-436. • KAUFMANN,P. (I958). " Porok6ratose de Mibelli." Paris : These. LEVER, W. F. (I967). " Histopathology of the Skin ", 4th Edition, pp. 62-63. Philadelphia : Lippincott. LOMBARDO, C. (I9O7). Cited by Kaufmann. LOVELL, S. (I945). Cited by Kaufmann. MmELLI V. (1893). Contributo allo studio della ipercheratosi dei canalo sudoriferi. Giornale Italiano Malattia Venero, 28, 313-355 . MIKHAtL, G. R. and WERTHEIM, F. W. (I968). Clinical variants of Porokeratosis (Mibelli). Archives of Dermatology, 98, IZ4-I3I. OBERSTE-LEHN, H. and MOLL, B. (1968). Porokeratosis Mibelli n n d StachelzeUcarcinom. Hautarzt, 19, 399-403 . REED, R . J . andLEoNE, P. (197o). Porokeratosis--amutant clonalkeratosisoftheepidermis. Archives of Dermatology, i o i , 34o-347 . ROBIN, H. H. (1953). Porokeratosis (Mibelli). Archives of Dermatology, 67, 526-527 • ROOK, A., WILKINSON, D. S. and EBLING, F. J. G. (I968). " Textbook of Dermatology ", Vol. 2, pp. lO62-1o63. Oxford. Blackwetl. SAVAGE, J. (1964). Porokeratosis (Mibelli) and carcinoma. British Journal of Dermatology, 76, 489. SAVAGE, J. and LEDERER, H. (1951). Porokeratosis (Mibelli). A case with extensive lesions. Results of animal inoculation. British Journal of Dermatology, 63, 187-192SEIF-EL-NASR, H., ALV, A. M. and ROAYA, F. (1962). Porokeratosis of Mibelli. Journal of the Egyptian Medical Association 45, 181-188. SMITH, P. (I95O). Cited by Johnston. VIGNE, P. (1942). Porok6ratose de MibeUi. Trois cas familiaux. Transformation n6oplasique chez l'un d'eux. Annales de Dermatologie et de Syphiligraphie, Paris, 2, 5-15.