torre-muir syndromea. an association with isolated sebaceous carcinoma

Torre-Muir Syndrome

An Association With Isolated Sebaceous Carcinoma

ROBERT GRAHAM, MB, MRCP,* PHILLIP MCKEE, MB, MRCPATH,? DAVID MCGIBBON, MB, MRCP,* AND EADIE HEYDERMAN, MB, MRCPATHt

Three cases of Torre-Muir syndrome are described in which isolated sebaceous carcinomas were associated with internal malignancy. The first was a 66-year-old woman who had a sebaceous carcinoma in association with carcinoma of the uterus, two adenocarcinomas of colon, carcinoma of renal pelvis and bladder, and a squamous cell carcinoma of the skin. The second was a 78-year-old woman who had a sebaceous carcinoma associated with carcinomas of the colon, ovary, and pancreas. The third patient had a sebaceous carcinoma associated with breast cancer. The subject is discussed and the previously reported cases reviewed.

Cancer 55:2868-2873. 1985.

HE ASSOCIATION of multiple sebaceous tumors and T keratoacanthoma with internal malignancy, first described separately by Muir and associates’ and Torre* in 1967, is well-recognized.

A hereditary association was first proposed by Bakker and Tjon A Joe3 in 1971, and the significant family history in Jakobiec’s4 case report of 1974 supported this suggestion. More recently, multiple sebaceous neoplasms, similar to those encountered in “Torre-Muir syndrome,” have been found in members of families exhibiting the “cancer family ~yndrome.”~

The majority of internal malignancies arise in the gastrointestinal system, predominantly colon,6 but tumors may arise in a variety of other sites, including the genitourinary tract.’ An association with non-Hodgkin’s lymphoma has also been described.8

There have been several previous reports of sebaceous carcinoma occurring in Torre-Muir syndrome, including Torre’s’ original case. However, these have all occurred in association with other sebaceous tumors.

Following recent studies of 17 cases of sebaceous carcinoma,’ we report 3 cases of isolated sebaceous carcinoma associated with internal malignancy.

From the Departments of *Dermatology and tHistopathology, St. Thomas’s Hospital, Lambeth Palace Road, London, United Kingdom.

Address for reprints: R. Graham, MB. MRCP, Department of Dermatology, The Royal Liverpool Hospital, Prescot Street, Liverpool L69 3BX.United Kingdom.

The authors thank Dr. K. V. Sanderson. Physician to the skin, The Skin Department, St. George’s Hospital, London.

Accepted for publication Ju ly 5 , 1984.

Case Reports

Cuse 1

In 1965, a 66-year-old woman developed over a 9-month period an ulcerated, red-colored crateriform lesion 2 cm in diameter on the anterior abdominal wall. It was widely excised and consisted of an irregular nonencapsulated yellow-red fatty nodule, which was ulcerating through the epidermis and also expanding to a depth of 1 cm into the subcutaneous fat. On microscopic examination (Fig. I ) the tumor was composed of a mixture of basophilic cells of presumed germinative (sebaceous) origin, with granular cytoplasm and increased numbers of eosinophilic nucleoli and mature-appearing sebaceous cells with delicate, foamy, slightly eosinophilic cytoplasm. Both cell populations showed varying degrees of pleomorphism and marked mitotic activity (Figs. 1 and 2). The tumor showed local invasion into the reticular dermis, but vascular and perineural spread was not seen. There was a moderately heavy surrounding mononuclear and plasma cell infiltrate. Fat stains (oil red 0) were positive within the areas of mature sebaceous differentiation.

The patient came from a family of 12 siblings, 10 of whom had already died of carcinoma of the colon. The 1 1 th. however, was still alive, having also had a colectomy for the same malignancy. The father had died of an unknown form of cancer and the mother had committed suicide. Further infor- mation on the cutaneous lesions within the family was un- available, and there was no known history of polyposis coli.

Her past history included a carcinoma of the uterus, successfully treated in 1942 by hysterectomy. Two years after the appearance of the initial cutaneous lesion, the patient underwent a left hemicolectomy for a well-differentiated adenocarcinoma of the splenic flexure of the colon. One year later, a nephrour- etectomy was performed for a well-differentiated transitional

2868

No. 1 2 TORRE-MUIR SYNDROME * Graham el al. 2869

cell carcinoma of the renal pelvis. During the same year, a well-differentiated squamous cell carcinoma, present for at least 6 months, was excised from the anterior chest wall.

In 1970, investigation of hematuria revealed a papillary transitional cell carcinoma of the bladder, which was managed by diathermy. The same year, following an acute episode of bowel obstruction, a mucus-secreting adenocarcinoma of the hepatic flexure of the colon was removed by right hemicolectomy. This was considered to be a new primary growth, rather than a recurrence. No lymph gland or metastatic involvement was detected.

The patient died at the age of 74 years from the combined effects of bladder carcinoma, continuing bowel obstruction, and general debility. Necropsy was not performed, and there are no traceable surviving relatives.

Cast! 2

In 1968, a 78-year-old woman with a 4 cm in diameter. yellow, fungating tumor of the scalp that had been present for several years was referred because of rapid enlargement over the preceding 6 months. A biopsy was performed and demonstrated similar changes macroscopically and microscopically to those seen in Case 1 (Fig. 3). Initial treatment with radiotherapy was unsuccessful, and complete excision was subse- quently performed.

The patient had had a past history of adenocarcinoma of the colon and of the ovary, both successfully managed surgxally. There was no other history of skin tumors, and no family history was available.

The patient died at the age of 84 years from carcinoma of the pancreas. Necropsy was not performed.

cuse 3

A 52-year-old woman presented with a lump in the breast; at the same time, a 3.5-cm nonulcerated. brown, egg-shaped nodule was detected on the thigh. The breast lesion was resected and found to be a poorly differentiated adenocarcinoma with local lymph node involvement. The nodule on the thigh, which had been present for an uncertain period, was also excised. Grossly, it had a pale gray color, and a fibrous consistency, with brown cystic spaces contained within. Micro- scopically, the histologic features were those of a sebaceous carcinoma (Fig. 4).

The patient remained well for 6 years, at which time she died of congestive cardiac failure and bronchopneumonia following a fall and fracture of the neck of the humerus. This could have been a pathologic fracture, but unfortunately necropsy was not performed. No family history was available.

Discussion

The descriptions of the three patients are consistent with previous reports of Torre-Muir syndrome except that they are distinguished by solitary carcinomas as their only sebaceous lesions.

All three tumors showed similar histopathologic fea-

FIG. 1 . Sebaceous carcinoma. Nests of irregular foamy cells are infiltrating into the reticular dermis. Notice the mitotic figure in the center of the field (H & E, original magnification X550).

tures typical of sebaceous ca r~ inoma .~ The tumors consisted of haphazard lobular arrangements of basophilic germinative and foamy mature sebaceous cells, with a variety of intermediate forms. Both of these cell populations showed nuclear and cytoplasmic pleomorphism, with increased numbers of normal and abnormal mitotic figures. This, together with a tendency to local invasion. distinguishes them from other more benign sebaceous lesions.

The association of Torre-Muir syndrome with sebaceous carcinomas was first reported in Torre’s* original

FIG. 2. Sebaceous carcinoma. Low-power view showing dual popu- lation of cells arranged in a lobular pattern. The smaller dark cells at the periphery contrast clearly with the centrally located foamy cells. (H & E, original magnification X63).

2870 CANCER June15 1985 VOl. 5s

FIG. 3. Sebaceous carcinoma showing a haphazard arrangement of predominantly small basophilic cells. Two mitoses are present (H & E, original magnification X400).

report and has since been confirmed by several authors. "-I4

Our first patient demonstrated an apparent association with an inherited form of large bowel cancer, as described by Ander~on.~ This may also represent the cutaneous phenotype linkage of Torre-Muir syndrome with the cancer family syndrome proposed by Lynch and col- l eague~ .~

The second patient survived the resection of her colonic and ovarian carcinomas without evidence of recurrence or metastases before she developed a solitary sebaceous carcinoma. The lesion recurred after initial treatment with radiotherapy, but this may represent the inadequacy of this form of treatment in the first-line management of sebaceous carcinomas, rather than the aggressive behavior of the primary.

There has only been one report of possible metastases from a sebaceous carcinoma in Torre-Muir ~yndrome . '~ It is uncertain in that report whether the lesion repre-

FIG. 4. Sebaceous carcinoma. Five mitotic figures are arrowed in this high-power field (H & E, original magnification X400).

sented metastatic sebaceous carcinoma or a primary tumor of the parotid. Although extraocular sebaceous carcinomas can behave aggre~sively,'~ this is unusual, and more often occurs with periocular lesions.'6 Jakobiec4 has reported the only case of Torre-Muir syndrome with sebaceous tumor involvement of the ocular adnexae. Although the lesion recurred on six occasions, it was believed histologically to be a sebaceous adenoma.

The findings and behavior in our patients' neoplasms support the observations made in previous of a relatively low malignant potential in both the cutaneous and the internal tumors of the Torre-Muir syndrome. Definite metastases have occurred from internal neoplasms in 8 of 40 cases so far reported (Table 1),'-8*10-25 which have included more than 85 different malignancies. There is one report" of metastatic deposits being successfully managed by surgical resection.

The occurrence in our third patient of a sebaceous carcinoma with carcinoma of the breast may be fortui-

TABLE 1. Review of Literature

Author Year Age*/sex Family history Cutaneous lesion Internal neoplasm Metastases

Muir er al.' 1967 31/M Negative

Tome2 1967 SO/M Unknown

Chapman and Finn19 1970 72/M Unknown 49lF Unknown

~ ~~~~ ~

Keratoacanthomat ( 5 ) Sebaceous adenoma

Sebaceous adenoma. Ca and epithelioma (multiple) keratoacanthomas (4)

Keratoacanthomat ( I ) Keratoacanthomat

(multiple)

Ca larynx ( I ) Ca colon (4) \. Negative Ca duodenum (2) j Ca ampulla of )

vatert ( 1) 1 Ca colon (1) 1 Negative

Ca larynx (1 ) Negative Ca larynx ( I ) Negative

No. 12 TORRE-MUIR SYNDROME * Gruhum et u/.

TABLE I . (Cuniinurd)

287 1


Bakkei and Tjon A Joe3

Rulon and Helwigl”

1971

1973

1974

1974

I974

I974

1974

1974

1976

1976

1977

1980

43/M

43/M

48/F

39/F

47/M

60/M

48/M

33/F

68/M

38/M

42/M

57/F

47/F

40/F

38/M

36/F

59/M

45/F

Possible Keratoacanthomat (4) Sebaceous adenoma ( I 1)

Squamous cell Ca (2) Sebaceous adenoma (10) Sebaceous hyperplasia ( I ) Others (8) Sebaceous adenoma (2) Sebaceous epithelioma ( I )

( 2 ) 1 Negative Ca stomach ( I )

Negative Ca colon (2) Negative

Internal malignancy positive cutaneous lesions negative

Unknown

Granuloma cell tumor of ovaryt ( 1 ) 1 Negative

1 Ca renal pelvis ( I ) Ca bladder ( I ) Ca colont ( I ) Ca ureter (1)

I 1 Sebaceous adenoma ( I I )

Others (4) Sebaceous adenoma (8) Sebaceous carcinoma? ( I ) Others ( I ) Sebaceous adenoma (2) Sebaceous epithelioma ( I ) Sebaceous adenomat

(multiple)

1 Negative Internal malignancy positive cutaneous lesions

Unknown Ca stomach (1) Ca colont (2)

Metastases Negative

Lynne-Davies and Brown”

Cutaneous lesions positive (sister) internal malignancy negative

Unknown

Ca colon ( I ) (POIYPS)

Metastases

Bitran and Pellettiere’’ Sebaceous adenoma (8) Sebaceous epithelioma ( I ) Others ( I )

Keratoacanthomat ( I ) Squamous cell Ca ( I )

Keratoacanthoma, sebaceous adenoma, epithelioma, and hyperplasiat (multiple)

Sebaceous adenomat (4) Basal cell epithelioma ( I ) Sebaceous hyperplasia ( I ) Others ( 1 ) Sebaceous adenoma ( I )

Sebaceous adenoma ( 6 ) Sebaceous carcinoma ( I ) Squamous cell Ca ( I ) Others ( I )

Sebaceous adenoma (5) Keratoacanthoma ( 3 ) Basal cell Ca ( I )

Ca vulva? ( I ) Ca uterus ( I )

Negative Metastases

Negative

Metastases 1 Poleksic”

Jakobiec*

Negative Ca colon ( 1 ) Ca esophagus ( I )

Ca colon ( I ) Cutaneous and internal malignancy positive

positive

unknown

Internal malignancy

Cutaneous lesions

Negative

Internal malignancy

Cutaneous lesions positive

negative

Cutaneous and internal malignancy positive

Cutaneous and internal malignancy negative

Scialli:; and W i ~ ~ k e l m a n n ’ ~

Ca colon ( I ) Negative

Ca colont ( I )

Ca colont ( I ) Ca larynx ( I ) Ca uterus ( I )

Negative

1 Negative

Leonard and Deaton”

1

Negative

Negative

Negative

Tschaiig ri a/.” Ca uterust ( I ) Ca colon ( 2 )

Reiffers d al ” Sebaceous hyperplasia, keratoacanthoma, squamous cell Ca, sebaceous adenoma, and epithelioma (multiple)

Keratoacanthomat ( I 1 ) Bowens disease vulva ( I )

Keratoacanthoma ( 3 ) Sebaceous adenoma (2) Sebaceous Ca ( I ) Sebaceous epithelioma (2) Sebaceous adenoma ( I )

Ca colon* ( I ) (polyps)

Stewail ri a/.’* Unknown Ca colon ( I )

Householder and Zeligmanl’

Internal malignancy

Cutaneous lesions

Internal malignancy

Cutaneous lesions

positive

negative

positive

negative

Ca colont (4) (polyps)

Ca duodenum ( I )

Ca uterus ( I ) Ca colon ( I )

1 1 Negative

Negative

2872 CANCER June 15 1985

TABLE 1 . (Conrinucd)

Vol. 55


Sebaceous epithelioma and adenoma. basal cell epithelioma. keratoacanthoma. and others (multiple)

Keratosest (multiple) Basal cell epitheliomat

(multiple)

Keratoses (multiple)

Keratosest (multiple)

Basal cell epithelioma. sebaceous hyperplasia, keratoacanthoma. and others (multiple)

Squamous cell C a t ( I ) Keratoses (multiple)

Sebaceous epithelioma ( I )

Ca colont ( I ) POlYPS

Negative Schwartz et 1980

1980

1980

1981

1981

1981

I982

61/M

76/M 49/M

63/M

43/F

69/M

41/M

30/F

40/F

5 I/M

6 l / F

59/M

64/M

47/F

46lM

Internal malignancy


negative

Anderson' Ca breast ( I ) Ca duodenum ( I ) Recurred ( 1 )

(POIYPS) Ca larynx? ( I )

(polyps) Ca bladder

(multiple) (polyps)

Ca colont ( I ) (POIYPS)

Negative Metastases Negative

Negative

Negative . Same family I

Metastases

Ca colon ( I )

Ca colont (3) Ca uterus (I )

Lynch ei a/.' Internal malignancy


negative

Siblings (both positive)

Metastases Negative

Sebaceous epithelioma ( I ) Keratoacanthomat ( I ) Sebaceous adenoma ( I ) Squamous cell Ca ( I )

Sebaceous adenoma and keratoacanthoma (multiple)

Keratoacanthomat (2) Squamous cell Ca ( I ) Sebaceous adenoma (3) Sebaceous carcinoma ( I ) Sebaceous hyperplasia Squamous cell Ca (6) Sebaceous hyperplasia ( I ) Sebaceous adenoma ( I )

Keratoacanthoma (2) Sebaceous adenoma ( I )

Ca uterus? ( I ) Ca colon ( I )

Ca colon ( I )

Lymphoma? ( I ) (lymphocytic)

Negative i Metastases

Descalzi and Rosenthal'

Worret et ul."

Unknown

Internal malignancy


negative

Cutaneous and internal malignancy positive

positive

negative

positive

possible

Internal malignancy

Cutaneous lesions

Internal malignancy

Cutaneous lesions

Ca colon ( 3 )

Ca ureter? ( I ) Ca colon ( I )

(POIYPS)

Ca colon ( I )

i 1 Negative

Negative

I ' Negative

I Negat've

3

7

Fahmy et ~ 1 . ' ~ Sebaceous adenomat ( 10) Keratoacanthoma (6) Squamous cell Ca (2)

Ca bladder (2) Ca ureter ( I ) Ca colon (4) Ca larynx ( I ) Ca bronchus ( I )

Sebaceous carcinoma ( I ) ? metastases ( I )

Sebaceous carcinoma ( I ) Squamous cell Ca ( I )

Current report 1984 43lF Internal malignancy


unknown

Ca uterus? ( I ) Ca colon ('7) Ca kidney and

ureter ( I ) Ca bladder ( I ) Ca colont ( I ) Ca ovary ( I ) Ca pancreas ( I) ('a breastt ( 1 )

1984 50/F

52/F

Unknown Sebaceous Ca ( I )

Unknown Sehaceous Ca -

* Age at presentation of first lesion. t Presenting lesion.

Ca: carcinoma; others: very common skin tumors.

No. 12 TORRE-MUIR SYNDROME - Graham et al. 2873

tous. However, the association of Torre-Muir syndrome with breast cancer has previously been d~cumen ted .~

Of the cases so far reported, there seems to be a slight male predominance (23 male: 17 female). Male patients seem more prone than female patients to develop foregut tumors (7 male:l female), and also appear to develop multiple tumors of the bowel more commonly (8 male: 3 female). There have been two cases of upper gastrointestinal carcinoma, both in male patients, one gastric” and one duodenal,’ which have metastasised. Upper gastrointestinal involvement may therefore confer a worse prognosis.

As, demonstrated with our patient, female patients frequently develop carcinoma of the uterus (7/16) and appear to be more prone to malignancy of the urinary tract, particularly transitional cell carcinomas (4 female: 2 male). This finding was remarked on by Anderson7 and could represent a slightly different phenotypic expression of the syndrome between the sexes.

It is uncertain whether the cases described by Chapman and Finn2’ can be classified as Torre-Muir syndrome. The report does, however, confirm the association with squamous cell carcinoma of the larynx originally documented by Muir et al.’ This appears to be particularly associated with keratoacanthomas as the cutaneous marker and, again, may represent a different variation in expression.

Of the cases documented in Table 1, seven have been associated with polyps in the colon, but there has been only one report associated with widespread gastrointestinal polyposis.6 This must be distinguished from “Gard- ner’s syndrome.”22 which has an autosomal dominant mode of inheritance, in which the cutaneous lesions include epidermoid cysts and desmoid tumors. Torre- Muir syndrome may present de novo, but there is often a variable family history of cutaneous and or internal tumors; when associated with the cancer family syndrome, an autosomal dominant mode of inheritance is found. ’

Multiple lesions of sebaceous hyperplasia and solitary keratoacanthomas are common skin tumors and therefore act as poor cutaneous markers of the Torre-Muir syndrome. Sebaceous adenomas, epitheliomas, and carcinomas, single or multiple, together with multiple keratoacanthomas, are uncommon, and therefore serve as potentially useful markers of the syndrome.

I n many of the cases so far reported the cutaneous lesions have preceded the internal malignancies, and although in two of our cases the situation was reversed, the frequently found overall low malignant potential means that early recognition of the condition is impor- tant. We would suggest that patients presenting with solitary as well as multiple sebaceous carcinomas, together with sebaceous adenomas, epitheliomas, and mul-

tiple keratoacanthomas should undergo appropriate screening and follow-up to aid the early detection of cases of Torre-Muir syndrome.

REFERENCES

I . Muir EG, Yates-Bell AJ, Barlow KA. Multiple primary carcino- mata of the colon, duodenum and larynx associated with keratoacanthoma of the face. Br J Surg 1967; 54:191-195.

2. Tome D. Multiple sebaceous tumours. Arch Dermatol 1968; 98:

3. Bakker PM, Tjon A Joe SS. Multiple sebaceous gland tumours with multiple turnours of internal organs. Dermutologica 1971; 142:

4. Jakobiec FA. Sebaceous adenoma of the eyelid and visceral malignancy. Am J Ophthalmol 1974; 78:952-960.

5. Lynch HT, Lynch PM. Pester J, Fusaro RM. The cancer family syndrome: Rare cutaneous phenotypic linkage of Torre’s syndrome. Arch Intern Med 1981; 141:607-611.

6. Schwartz RA. Flieger DN, Saied NK. The Torre syndrome with gastrointestinal polyposis. Arch Dermatol 1980; 1 I6:3 13-3 14.

7. Anderson DE. An inherited form of large bowel cancer: Muir’s syndrome. Cancer 1980; 45:1103-1107.

8. Descalzi ME, Rosenthal S. Sebaceous adenomas and keratoacanthomas in a patient with malignant lymphoma: A new form of Torre’s syndrome. Cuiis 1981: 28:169-170.

9. Graham RM, McKee PH, McGibbon D. Sebaceous carcinoma. Clin Exp Dermaiol 1984; 9:466-47 1.

10. Rulon DB, Helwig EB. Multiple sebaceous neoplasms of the skin: An association with multiple visceral carcinomas especially of the colon. Am J Clin Paihol 1973; 60:745-752.

I I . Leonard DD, Deaton WR. Multiple sebaceous gland tumors and visceral carcinomas. Arch Dermaiol 1974; 1 10:917-920.

12. Householder MS, Zeligman I. Sebaceous neoplasms associated with visceral carcinomas. Arch Dermaiol 1980; 1 16:61-64.

13. Worret W1, Burgdorf WH, Fahmy A, Pitha J. Tome-Muir syndrome talgdnisenneoplasien, keratoakanthome, multiple karzinome and vererburg. Hairtarzt 1981; 32:5 19-524.

14. Fahmy A, Burgdorf WH, Schosser RH, Pitha J. Tome-Muir syndrome: Report of a case and re-evaluation of the dermatopathological features. Cancer 1982: 49: 1898- 1903.

15. King DT, Hirose FM, Gurevitch AW. Sebaceous carcinoma of the skin with Visceral Metastases. Arch Dermatol 1979; I75:862-863.

16. Ni C. Sear1 SS, Kuo PK, Chu FR, Chung CS, Albert DM. Sebaceous cell carcinomas of the ocular adnexa. Int Ophthalmol C‘lin

17. Tschang TP, Poulos E, Ho CK, Kuo TT. Multiple sebaceous adenomas and internal malignant disease: A case report with chro- mosomal analysis. Hum Palhol 1976; 7:589-594.

18. Stewart WM, Hemet W. Thomine E, Gueville RM. Kerato- acanthomas multiples et carcinomas visceraux: Syndrome de Torre. Ann Dermatol Venereol 1977; 104:622-626.

19. Chapman RS, Finn OA. Carcinoma of the larynx in two patients with keratoacanthoma. Br J Dermatol 1974; 90:685-688.

20. Bitran J, Pellettiere. Multiple sebaceous gland tumors and internal carcinoma: Torre’s syndrome. Cancer 1974; 33335-836.

21. Gardner EJ. Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas. fibromas and epidermal cysts. Am J H i m Genet 1962; 14: 376-389.

22. Lynne-Davies G, Brown J. Multiple sebaceous gland tumors associated with polyposis of the colon and bony abnormalities. Can

23. Poleksic S . Keratoacanthoma and multiple carcinomas. Br J Dermaiol 1974; 9 1:46 1-463.

24. Sciallis GF, Winkelmann RK. Multiple sebaceous adenomas and gastrointestinal carcinoma. Arch Dermutol 1974; 1 10:9 13-9 16.

25. Reiffers J, Laugier P, Hunziker N. Hyperplasia stbackes. kera- toacanthomes, epitheliomas au visage et cancer due C6lon: Une nouvelle entit&? Dermatolngica 1976; 153:23-33.

549-55 1.

50-57.

1982; 22123-6 I .

bled AS SO^ J 1974; I10:1377-1379.

torre-muir syndromea. an association with isolated sebaceous carcinoma

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