British Journal ofPlastic Surgery (19;15), 28, 331-334
METASTATIC BASAL CELL CARCINOMA WITH SQUAMOUS APPEARANCES IN TI-IE NAEVOID BASAL CELL CARCINOMA SYNDROME By
KEVIN
J. MURPHY,B.Sc., F.R.A.C.P.
Deputy Medical Superintendent, Princess Alexandra Hospital, Ipswich Road, Woolloongabba,Queensland, Australia, 4102
THE naevoid basal cell carcinoma syndrome is an association of multiple basal cell carcinomas with jaw cysts, rib anomalies and other features (Howell and Care, 1959; Gorlin and Goltz, 1960). The adjective “naevoid” is used to imply that the basal cell carcinomas have a constitutional basis, a tendency to appear early in life and to be inherited on an autosomal dominant basis. They are histologically indistinguishable from the usual basal cell carcinoma (Mason et al., 1965). The following case record shows that these tumours can also metastasise, although this is very rare for basal cell carcinomas (Willis, 1952). CASE REPORT An unmarried man who worked in a refrigerated warehouse, was previously reported (Murphy, 1969) at the age of 46 years as an example of the naevoid basal cell carcinoma syndrome. He had multi-locular cysts in the mandible, multiple basal cell carcinomas, bifid ribs, calcification of subcutaneous tissues and of the falx cerebri, and spina bifida occulta. At the time of that report the skull and the pelvic bones were intact. He returned for review 4 years later with an ulcerating infected basal cell carcinoma of the vertex of the scalp IO cm in diameter, which he stated had been present for 7 months only (Fig. I), an ulcerating basal cell carcinoma of the lower forearm 5 cm in diameter, and an early basal cell carcinoma of the right side of the neck I cm in diameter. X-rays of the skull showed a large area of bone destruction in the frontal region, extending across the midline, and a left carotid arteriogram showed slight downward displacement of the upper branches of the anterior cerebral artery. Surgical excision with a 2 cm margin at the periphery was attempted. In the centre, the tumour had infiltrated through the skull bones, the dura was macroscopically involved and the superior sagittal sinus was partially occluded. A fascia lata graft was used to replace the excised dura and a rotation flap from the occiput covered the skin defect. Histological examination confirmed the typical appearances of a basal cell carcinoma and showed the presence of nests of carcinoma cells through the dura. The patient had 4 grand mal fits in the 24 hours following operation, but then recovered consciousness and progressed uneventfully. The lesion on the left wrist was confirmed by biopsy to be a typical basal cell carcinoma but it was also found to be infiltrating the median nerve; radiotherapy was unsuccessful, and he eventually required an amputation through the forearm. The patient returned 18 months later complaining of pain over the left sacral region, and weakness of the left leg. X-rays showed an area of bone destruction involving the left side of the sacrum. This was explored and found to be a mass of carcinoma tissue, deep to the deep fascia. There was no overlying skin lesion. Biopsy confirmed a carcinoma, infiltrating bone, and composed of irregular pleomorphic nuclei with frequent mitoses and rather ill-defined boundaries. Some areas were showing keratin formation and there were areas of apparent production of proteinaceous matrix material. The appearances were those of an anaplastic carcinoma with some squamous differentiation (Fig. 2). No primary squamous tumour was found. A course of methotrexate gave temporary relief from pain, but the tumour subsequently enlarged with further bone destruction (Fig. 3) and the production of a neoplastic mass which filled the left side of the cavity of the pelvis and extended into the left side of the abdomen. The patient died 3 years after the surgical excision. Post-mortem examination showed the 331
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332
FIG.
FIG. 2.
I.
Basal cell carcinoma
JOURNAL
OF
PLASTIC
SURGERY
of the scalp, stated to have been present for 7 months only.
Portion of the tumour deposit in the pelvis, showing its anaplastic nature, and keratin production. H&E. x550. FIG. 3.
X-ray
of the pelvis, showing the extent of bone destruction.
METASTATIC BASAL CELL CARCINOMA
333
same features of a massive tumour approximately 16 x 16 x 16 cm with extensive areas of keratin and with patches of squamous cells. Numerous giant cells were present, usually related to keratin, and there were areas of anaplastic cells most closely resembling basal cells. An area of bone from the edge of the skull defect showed persisting basal cell carcinoma with areas of squamous differentiation. There were no secondary deposits in the spinal cord or in the dura. In the region of the cauda equina the sacrum surrounding the spinal canal was completely destroyed and replaced by tumour tissue. Originally it had been postulated that the deposit in the pelvis had been due to seeding down the spinal canal following infiltration of the dura, but, in the absence of other evidence of seeding through the canal, it is now suggested that the secondary deposit was caused by haematological spread following infiltration of the sagittal sinus or other vessels. The skeletal features of the naevoid basal cell carcinoma syndrome were confirmed and the jaw cysts, the largest of which measured 3 x 2 x 2 cm, were lined with stratified squamous epithelium, and filled with keratin. There was no malignant change within these cysts.
DISCUSSION Most reported cases of metastatic basal cell carcinoma have followed a prolonged course, with several recurrences and many treatments by surgery and radiotherapy (Hirshowitz and Mahler, 1968; Wermuth and Fajardo, 1970). The latter authors accepted the reports of 76 cases of metastatic basal cell carcinomas in the literature, and postulated that cachectic patients may develop an imrmmological deficit severe enough for them to tolerate distant implants of a tumour that ordinarily grows only in the skin. Cornelius (1972) accepted reports of 71 cases of metastasising basal cell carcinoma, and postulated that the trauma of previous therapy caused a loss of the normal stromal dependence of the basal cell carcinoma; he thought that stromal independence was necessary for survival of metastases of this tumour, but that once such independence was gained the tumour should be regarded as highly malignant. The patient reported here stated that the scalp lesion had been present for 7 months only; there had been no prior surgery or radiation therapy to this region; he could not be considered cachectic at the time the metastasis appeared, and he had a solitary secondary deposit. These features negate many of the above opinions, and indicate a rapidly growing invasive tumour. They also contradict the statement that the tumours in the naevoid basal cell carcinoma syndrome do not invade deeply (Lever, 1967). The original biopsies of all tumours in this patient showed typical basal cell carcinoma, as is usual in the naevoid basal cell carcinoma syndrome (Mason et al.). But the secondary deposit in the pelvis, and the persisting tumour in the skull, showed areas ofsquamous cells and keratin formation, justifying the title baso-squamous (or transitional, or metatypical-cell) carcinoma (Allen, 1971). Allen regarded such areas of keratinised squamous ceils as evidence of maturation of basal cells, rather than as indicating dedifferentiation. The behaviour of this tumour, and its anaplastic appearance in other areas, support the opposite view, that a baso-squamous appearance indicates a higher degree of malignancy (Bore& 1973). Lever believed that squamous change in a basal cell carcinoma was impossible; this patient confirms that it can happen, even in constitutionally determined basal cell tumours.
SUMMARY
A patient with the naevoid basal cell carcinoma syndrome developed a secondary carcinomatous deposit in the pelvis. Persisting tumour in the skull and the secondary deposit in the pelvis contained areas of squamous differentiation. This confirms that the appearances of baso-squamous (or transitional or metatypical-cell) carcinoma can
BRITISH
334
JOURNAL
OF
PLASTIC
SURGERY
develop from typical basal cell carcinoma which had not been subjected to radiotherapy or to more than one surgical excision. I am indebted to Dr R. Quinn for the histology reports, and to Dr K. J. Brown for details of plastic surgical management. REFERENCES A. C. (1971). Skin. Chapter 39 in “Pathology”. edited by Anderson, W. A. D., 6th edition, volume 2, p. 1651. St Louis: Mosby. BOREL, D. M. (1973). Cutaneous basosquamous carcinoma. Review of the literature and report of 35 cases. Archives of Pathology, 95, 293-297. Archives of CORNELIUS,C. E. (1972). Bone. A site of metastatic basal cell carcinoma. Surgery, 104, 848-850. GORLIN, R. J. and GOLTZ, R. W. (r960). Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. The New EnglandJournal of Medicine, 262, 908-912. HIRSHOWITZ,B. and MAHLER,D. (1968). Unusual case of multiple basal cell carcinoma with metastasis to the parotid lymph gland. Cancer, 22, 654-657. Basal-cell nevus: its relationshin to multiple HOWELL, T. B. and CARO, M. R. (19so). . cutaneous cancers and associated anomalies of development. Archives of Dermatolo>y, ALLEN,
___I
79, 67-80.
of the Skin” , 4th Edition, pp. $38 and 590. LEVER, W. F. (1967). “Histopathology Philadelphia: Lippincott. MASON. T. K.. HELWIG. E. B. and GRAHAM.T. H. (196tl. Patholoav of the nevoid basal cell carcinoma syndrome. Archives of l%hologj, ~9,‘401-408. -I MURPHY, K. J. (1969). Subcutaneous calcification in the naevoid basal-cell carcinoma syndrome: response to parathyroid hormone and relationship to pseudo-hypoparathyroidism. Clinical Radiology, 20, 287-293. WERMUTH,B. M. and FAJARDO,L. F. (x970). Metastatic basal cell carcinoma. A review. Archives of Pathology, 90, 458-462.
WILLIS, R. A. (1952). Butterworth.
“The Spread of Tumours
in the Human Body”, p. 94.
London:
METASTATIC BASAL CELL CARCINOMA WITH SQUAMOUS APPEARANCES IN TI-IE NAEVOID BASAL CELL CARCINOMA SYNDROME By
KEVIN
J. MURPHY,B.Sc., F.R.A.C.P.
Deputy Medical Superintendent, Princess Alexandra Hospital, Ipswich Road, Woolloongabba,Queensland, Australia, 4102
THE naevoid basal cell carcinoma syndrome is an association of multiple basal cell carcinomas with jaw cysts, rib anomalies and other features (Howell and Care, 1959; Gorlin and Goltz, 1960). The adjective “naevoid” is used to imply that the basal cell carcinomas have a constitutional basis, a tendency to appear early in life and to be inherited on an autosomal dominant basis. They are histologically indistinguishable from the usual basal cell carcinoma (Mason et al., 1965). The following case record shows that these tumours can also metastasise, although this is very rare for basal cell carcinomas (Willis, 1952). CASE REPORT An unmarried man who worked in a refrigerated warehouse, was previously reported (Murphy, 1969) at the age of 46 years as an example of the naevoid basal cell carcinoma syndrome. He had multi-locular cysts in the mandible, multiple basal cell carcinomas, bifid ribs, calcification of subcutaneous tissues and of the falx cerebri, and spina bifida occulta. At the time of that report the skull and the pelvic bones were intact. He returned for review 4 years later with an ulcerating infected basal cell carcinoma of the vertex of the scalp IO cm in diameter, which he stated had been present for 7 months only (Fig. I), an ulcerating basal cell carcinoma of the lower forearm 5 cm in diameter, and an early basal cell carcinoma of the right side of the neck I cm in diameter. X-rays of the skull showed a large area of bone destruction in the frontal region, extending across the midline, and a left carotid arteriogram showed slight downward displacement of the upper branches of the anterior cerebral artery. Surgical excision with a 2 cm margin at the periphery was attempted. In the centre, the tumour had infiltrated through the skull bones, the dura was macroscopically involved and the superior sagittal sinus was partially occluded. A fascia lata graft was used to replace the excised dura and a rotation flap from the occiput covered the skin defect. Histological examination confirmed the typical appearances of a basal cell carcinoma and showed the presence of nests of carcinoma cells through the dura. The patient had 4 grand mal fits in the 24 hours following operation, but then recovered consciousness and progressed uneventfully. The lesion on the left wrist was confirmed by biopsy to be a typical basal cell carcinoma but it was also found to be infiltrating the median nerve; radiotherapy was unsuccessful, and he eventually required an amputation through the forearm. The patient returned 18 months later complaining of pain over the left sacral region, and weakness of the left leg. X-rays showed an area of bone destruction involving the left side of the sacrum. This was explored and found to be a mass of carcinoma tissue, deep to the deep fascia. There was no overlying skin lesion. Biopsy confirmed a carcinoma, infiltrating bone, and composed of irregular pleomorphic nuclei with frequent mitoses and rather ill-defined boundaries. Some areas were showing keratin formation and there were areas of apparent production of proteinaceous matrix material. The appearances were those of an anaplastic carcinoma with some squamous differentiation (Fig. 2). No primary squamous tumour was found. A course of methotrexate gave temporary relief from pain, but the tumour subsequently enlarged with further bone destruction (Fig. 3) and the production of a neoplastic mass which filled the left side of the cavity of the pelvis and extended into the left side of the abdomen. The patient died 3 years after the surgical excision. Post-mortem examination showed the 331
BRITISH
332
FIG.
FIG. 2.
I.
Basal cell carcinoma
JOURNAL
OF
PLASTIC
SURGERY
of the scalp, stated to have been present for 7 months only.
Portion of the tumour deposit in the pelvis, showing its anaplastic nature, and keratin production. H&E. x550. FIG. 3.
X-ray
of the pelvis, showing the extent of bone destruction.
METASTATIC BASAL CELL CARCINOMA
333
same features of a massive tumour approximately 16 x 16 x 16 cm with extensive areas of keratin and with patches of squamous cells. Numerous giant cells were present, usually related to keratin, and there were areas of anaplastic cells most closely resembling basal cells. An area of bone from the edge of the skull defect showed persisting basal cell carcinoma with areas of squamous differentiation. There were no secondary deposits in the spinal cord or in the dura. In the region of the cauda equina the sacrum surrounding the spinal canal was completely destroyed and replaced by tumour tissue. Originally it had been postulated that the deposit in the pelvis had been due to seeding down the spinal canal following infiltration of the dura, but, in the absence of other evidence of seeding through the canal, it is now suggested that the secondary deposit was caused by haematological spread following infiltration of the sagittal sinus or other vessels. The skeletal features of the naevoid basal cell carcinoma syndrome were confirmed and the jaw cysts, the largest of which measured 3 x 2 x 2 cm, were lined with stratified squamous epithelium, and filled with keratin. There was no malignant change within these cysts.
DISCUSSION Most reported cases of metastatic basal cell carcinoma have followed a prolonged course, with several recurrences and many treatments by surgery and radiotherapy (Hirshowitz and Mahler, 1968; Wermuth and Fajardo, 1970). The latter authors accepted the reports of 76 cases of metastatic basal cell carcinomas in the literature, and postulated that cachectic patients may develop an imrmmological deficit severe enough for them to tolerate distant implants of a tumour that ordinarily grows only in the skin. Cornelius (1972) accepted reports of 71 cases of metastasising basal cell carcinoma, and postulated that the trauma of previous therapy caused a loss of the normal stromal dependence of the basal cell carcinoma; he thought that stromal independence was necessary for survival of metastases of this tumour, but that once such independence was gained the tumour should be regarded as highly malignant. The patient reported here stated that the scalp lesion had been present for 7 months only; there had been no prior surgery or radiation therapy to this region; he could not be considered cachectic at the time the metastasis appeared, and he had a solitary secondary deposit. These features negate many of the above opinions, and indicate a rapidly growing invasive tumour. They also contradict the statement that the tumours in the naevoid basal cell carcinoma syndrome do not invade deeply (Lever, 1967). The original biopsies of all tumours in this patient showed typical basal cell carcinoma, as is usual in the naevoid basal cell carcinoma syndrome (Mason et al.). But the secondary deposit in the pelvis, and the persisting tumour in the skull, showed areas ofsquamous cells and keratin formation, justifying the title baso-squamous (or transitional, or metatypical-cell) carcinoma (Allen, 1971). Allen regarded such areas of keratinised squamous ceils as evidence of maturation of basal cells, rather than as indicating dedifferentiation. The behaviour of this tumour, and its anaplastic appearance in other areas, support the opposite view, that a baso-squamous appearance indicates a higher degree of malignancy (Bore& 1973). Lever believed that squamous change in a basal cell carcinoma was impossible; this patient confirms that it can happen, even in constitutionally determined basal cell tumours.
SUMMARY
A patient with the naevoid basal cell carcinoma syndrome developed a secondary carcinomatous deposit in the pelvis. Persisting tumour in the skull and the secondary deposit in the pelvis contained areas of squamous differentiation. This confirms that the appearances of baso-squamous (or transitional or metatypical-cell) carcinoma can
BRITISH
334
JOURNAL
OF
PLASTIC
SURGERY
develop from typical basal cell carcinoma which had not been subjected to radiotherapy or to more than one surgical excision. I am indebted to Dr R. Quinn for the histology reports, and to Dr K. J. Brown for details of plastic surgical management. REFERENCES A. C. (1971). Skin. Chapter 39 in “Pathology”. edited by Anderson, W. A. D., 6th edition, volume 2, p. 1651. St Louis: Mosby. BOREL, D. M. (1973). Cutaneous basosquamous carcinoma. Review of the literature and report of 35 cases. Archives of Pathology, 95, 293-297. Archives of CORNELIUS,C. E. (1972). Bone. A site of metastatic basal cell carcinoma. Surgery, 104, 848-850. GORLIN, R. J. and GOLTZ, R. W. (r960). Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. The New EnglandJournal of Medicine, 262, 908-912. HIRSHOWITZ,B. and MAHLER,D. (1968). Unusual case of multiple basal cell carcinoma with metastasis to the parotid lymph gland. Cancer, 22, 654-657. Basal-cell nevus: its relationshin to multiple HOWELL, T. B. and CARO, M. R. (19so). . cutaneous cancers and associated anomalies of development. Archives of Dermatolo>y, ALLEN,
___I
79, 67-80.
of the Skin” , 4th Edition, pp. $38 and 590. LEVER, W. F. (1967). “Histopathology Philadelphia: Lippincott. MASON. T. K.. HELWIG. E. B. and GRAHAM.T. H. (196tl. Patholoav of the nevoid basal cell carcinoma syndrome. Archives of l%hologj, ~9,‘401-408. -I MURPHY, K. J. (1969). Subcutaneous calcification in the naevoid basal-cell carcinoma syndrome: response to parathyroid hormone and relationship to pseudo-hypoparathyroidism. Clinical Radiology, 20, 287-293. WERMUTH,B. M. and FAJARDO,L. F. (x970). Metastatic basal cell carcinoma. A review. Archives of Pathology, 90, 458-462.
WILLIS, R. A. (1952). Butterworth.
“The Spread of Tumours
in the Human Body”, p. 94.
London:
