Radiation therapy and chemotherapy in malignant sweat gland tumors

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Radiation therapy and chemotherapy in malignant sweat gland tumors* Richard Whittington, Lieutenant Commander, MC, USNR,** Mark E. Browning, Lieutenant Commander, MC, USN,*** George R. Farrell, Commander, MC, USN,**** and Arjang Miremadi, Commander, MC, USN***** Bethesda, MD A case of a 62-year-old man with an incompletely resected recurrent adnexal skin tumor is reported. The patient had a complete resolution of tumor with external beam radiation therapy. The tumor metastasized to lung and pleura, and the patient's tumor nodules stabilized with methotrexate. The reported experience with radiation and chemotherapy for this tumor is reviewed and is then contrasted with the observations in this patient. Currently available radiation technics may be of value in managing patients with unresectable tumors. (J AM ACAD DERMATOL15:1093-1097, 1986.)

Because carcinomas of the eccrine sweat glands are rare, there are few data on the results of their treatment. Most patients are managed by surgical excision of the lesion, although selected patients may receive radiation therapy or chemotherapy because of recurrence or the risk o f recurrence. Relatively few patients have been treated with modem radiation therapy technics or chemotherapy, and the older literature is unclear as to the efficacy of these modalities.

CASE REPORT A 62-year-old man noted a small furuncle in the left temporal skin in July 1982. Initially he was able to express some purulent material from the lesion. The lesion doubled in size over the course of 3 months and began to bleed. The patient was evaluated by a derFrom the Radiation Oncology Branch, Department of Radiology,** the Medical Oncology Branch, Department of Internal Medicine,*** the Department of Otolaryngology,**** and the Department of Pathology,***** Naval Hospital. Reprint requests to: Dr. Richard Whittington, Department of Radiation Therapy, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104/215-662-6515. *The opinions and assertions contained herein are those of the authors and are not to be construed as official or as representing those of the Department of Defense or the Department of the Navy.

matologist, and the lesion was diagnosed clinically as a basal cell epithelioma and cauterized. One month after the cauterization, a recurrent lesion was excised. Histologic diagnosis of the excised lesion was adnexal skin tumor of the eccrine type. Two weeks later a satellite nodule was excised from the area of the left eyebrow, 3 cm from the incision, and again the diagnosis was an adnexal skin tumor. The patient was referred to the Naval Hospital, Bethesda, MD, for further evaluation and treatment in November 1982. On initial evaluation in this institution a 4-ram recurrence was noted in the incision, as well as a 1-cm preauricular lymph node. The general physical examination, including that of the skin and of the head and neck, was unremarkable. Since the preauricular mass was thought possibly to involve the parotid gland, the patient underwent a left superficial parotidectomy and excision of the nodule. The preauricular mass was a lymph node with metastatic adnexal skin tumor grossly invading the superficial and deep lobes of the parotid gland. Gross residual tumor was left in the deep lobe. Histologic examination of tumor in skin, parotid gland, and lymph node revealed poorly differentiated tumor nodules composed of anastomosing sheets and cords of the ceils with mild desmoplasia (Figs. 1 and 2). In some areas the tumor cells were spindle-shaped. Many areas of squamous differentiation with pearls were noted in all the sections. Mitotic figures were 1093

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Whittington et al

T a b l e I. Results o f radiation therapy in treating adnexal skin tumors Year

Case No.

Source

reported

Region treated

NS

Volume of tumor

1

Eliott and Ramsay 3

1956

2

Stout and Cooley 4

1951

R side of chest wall and axilla Forearm

3

Stout and Cooley 4

1951

Axilla

lxlcm

4 5 6

Stout and Cooley 4 Stout and Cooley 4 Stout and Cooley 4

1951 1951 1951

Inner canthus L brachium R breast

Adjuvant post resection 2x3cm 7x5X3cm

7

Keasbey and Hadley s

1954

R temple

2 X 1.6cm

8

Keasbey and Hadley s

1954

R side of neck

NS

9 10

Teloh 6 Mackenzie v

1955 1957

6x6×3cm Adjuvant post resection

11

Kersting s

1963

Skull Finger, axilla, epitrochlear nodes Nose

12

Horn 9

1944

Axilla

Adjuvant post resection

t3

Hirsch et aP °

1971

l×lcm

14

Hirsch et al to

1971

L femoral skin, inguinal nodes R foot

Adjuvant post resection

15

Hirsch et al to

1971

R foot

Adjuvant post resection

16

Roach tt

1983

Adjuvant post resection

I7 18

MilleP 2 Our case

1967 1985

R thigh, inguinal nodes Not specified Left side of face

3 x 2.5cm

2.6 cm

Not specified Gross residual tumor in parotid gland, neck nodes

CR: Complete response; NED: no evidence of disease; NS: not specified.

markedly increased. The tumor in the salivary gland was located within the connective tissue between the lobules and had no connection with secretory elements of the gland. The tumor in the skin showed no connection to the epidermis. Mucin stain revealed no mucin production by tumor cells; however, periodic acid-Schiff stain was positive, suggesting an epithelial origin of tumor. It is our belief that this malignant tumor originated from one of the adnexal elements of the skin. Four weeks following surgery the patient began postoperative radiation therapy. A 1.5-era, clinically in-

volved left jugular-digastric lymph node was palpated at the beginning of radiation therapy. All sites of tumor excision with a 5-cm margin were treated in conjunction with the ipsilateral cervical and supraclavicular lymph nodes. A minimum tumor dose of 4,600 fads was delivered to the anterior and lateral fields. Wedge filters were used on both fields to produce a homogeneous radiation dose throughout the treatment volume. Bolus material was used to ensure an adequate dose to the skin. The suprahyoid cervical lymph nodes and all tumor sites with a 3-crn margin were treated to 5,600 rads. The parotid gland, temporal skin, and jugular-

Volume 15 Number 5, Part 2 November, 1986

Beam

Malignant sweat gland tumors

I

Dose

I

Result

1095

Follow-upduration, status

220 kV(p)

2,000 R/air

NED

2 yr

Radium implant

7,740 mg/hr

No response

NS

NS

NS NS NS

NS 5,000 rads NS

No response; metastases Relapse CR No response

NS

3,500 rads

NS

NS

Slow and incomplete regression Brief regression

1,000 kV(p) 6OCo

2,500 rads 5,000 rads

No response NED

3 yr; dead from local and distant metastases 27 mo; dead with local recurrence and distant 18 mo; dead from local invasion Relapsed soon after treatment Dead with local and distant disease, 31 mo 8 too; died with distant metastases; locally controlled with resection Died with local tumor and bone metastases 4 too; dead of local progression Follow-up indeterminate

Several courses of Ra, x-ray 250 kV(p)

NS

No response

6 too; controlled post excision

5,950 rads

NED

NS

NS

No response

Dead from distant metastases, 16 yr Not reported

NS

NS

NED

NS

NS

Local relapse

NS

5,500 rads

Local relapse

NS 6°Co, 18 meV electrons

NS 7,050 rads

"Palliation" NED

digastric node were boosted with an electron beam to a dose of 7,050 rads in 8 weeks. At the completion of treatment there was no residual palpable abnormality. There was mild to moderate buccal mucositis. A subsequent chest roentgenogram and bone scans were unremarkable until 6 months following completion of radiation therapy, when two nodules were noted in the right lung on routine follow-up radiography. Metastatic evaluation was otherwise unremarkable, and a thoracotomy was performed after other attempts at diagnosis were unsuccessful. Diffuse seeding of the visceral and parietal pleura, as well as of the parenchymal nodules, was noted. Biopsy of several nodules was again interpreted as metastatic adnexal skin tumor. Fol-

Dead of unrelated causes, 21/2 yr 1 yr; dead of disease following below-knee amputation with distant metastases 26 mo; dead with local and distant metastases 5 too; dead with disease Dead of metastases 31 mo after treatment; no evidence of local failure

low-up examination of the head and neck showed mild subcutaneous fibrosis without atrophy or telangiectasis. No skin nodules or adenopathy was noted in the irradiated volume. The patient was treated weekly with methotrexate, 40 mg/m 2. Therapy was given intravenously for I0 weeks and, subsequently, orally. The nodules stabilized for 5 months, with some nodules showing minimal regression, and no new lesions were noted. New nodules were noted on the chest radiograph of September 1984, and a bone scan was consistent with multiple metastases. There was no response to increased doses of methotrexate. The patient died of respiratory failure with metastases to the pleura and pericardium 23

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Journal of the American Academy of Dermatology

Fig. 1. Section from an initial excision of a skin tumor, demonstrating a poorly differentiated tumor with an area of squamous differentiation and marked desmopIasia. ( x 250.)

Fig. 2. Section from an initial excision of a skin tumor, showing anastamosing sheets of poorly differentiated tumor cells with minute loci of squamous differentiation.

months after beginning therapy. An autopsy was not performed, but there was no clinical evidence of recurrent tumor in the region of the head and neck.

skin tumors. Patient 12 (Table I) was briefly treated with chlorambucil in 1943, one year before death, without response. Patient 16 was treated with 5fluorouracil and later with cis-platinum and cytosine arabinoside without response. A short-lived response was seen with 13-cis-retinoic acid. One other patient was treated with mitomycin, doxorubicin, and 5-fluorouracil without response. ~3Although the patient whose case we report did not have an objective response, the disease stabilized for 5 months. There are not enough cases currently reported to evaluate the natural history of these tumors or the value of other therapy in addition to surgery. In the two largest series the behavior of the tumor differed markedly. In Miller's review ~2 in 1967, local recurrences occurred in 17 of 39 patients (43%), whereas distant metastases were seen in 23 of 39 patients (59%). The more recent review by Mehregan et al 2 reports local recurrence in 5

DISCUSSION The role o f radiation therapy and chemotherapy in the management of eccrine sweat gland tumors is unclear. One source reports that the tumors are radiosensitive,~ but a recent review states that they do not respond to radiation therapy. 2 There are seventeen cases reported in the literature in which radiation was used in the management of adnexal skin tumors (Table I). There are relatively few cases in which the quality of the radiation or the dose has been reported. Many of these cases antedate the development of m o d e m radiation therapy treatment planning and modern treatment machines. There are three cases in the literature in which chemotherapy was used to treat metastatic adnexal

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of 35 patients (17%) and metastases in 2 of 35 patients (6%). On the basis of the observations in this patient, it appears that the role of radiation therapy in this disease needs to be reassessed. It is not clear whether the poor results reported previously were due to true resistance of the tumor to radiation or to limitations in dose and field size as a result of the available equipment. With currently available equipment, this patient had a durable complete response of gross residual tumor with what are currently conventional doses of radiation. The recent results with surgery are very good, but radiation should be considered for inclusion in the plan of treatment of recurrent or unresectable lesions. The responses reported with chemotherapy are interesting, and it should be considered in patients with metastatic tumors, although there are too few reports to suggest the use of any specific regimen. REFERENCES

I. Hashimoto K, Lever WF: Appendage tumors of the skin. Springfield, IL, 1968, Charles C. Thomas, Publisher, pp. 150-154.

Malignant sweat gland tumors

2, Mehregan AH, Hashimoto K, Rahbari H: Eccrine adenocarcinoma: A clinicopathologic study of 35 cases. Arch Dermatol 119:104-114, 1983. 3. Elliott GB, Ramsay DW: Sweat gland carcinoma. Ann Surg 144:99-106, 1956. 4. Stout AP, Cooley SG: Carcinoma of the sweat glands. Cancer 4:521-536, 1951. 5. Keasbey LE, Hadley GG: Clear-cell hidradenoma: Report of three cases with widespread metastases. Cancer 7-934-952, 1954. 6. Teloh HA: Sweat gland carcinoma. Cancer 8:1003-1008, 1955. 7. MacKenzie DH: A clear-cell hidradenoma with metastases. Cancer 10:1021-1023, 1957. 8. Kersting DW: Clear celI hidradenoma and hidradenocarcinoma. Arch Dermatol Syphilol 87:323-333, 1963. 9. Horn PC Jr: Malignant papillary eystadenoma of sweat glands with metastases to the regional lymph nodes. Surgery 16:348-355, 1944. 10. Hirsch LF, Enterline HT, Rosato EF, et al: Sweat gland carcinoma. Ann Surg 174:283-286, 1971. 11. Roach M: A malignant ecerine poroma responds to isotretinoin (13-cis-retinoic acid). Ann Intern Med 99:486487, 1983. 12. Miller WL: Sweat gland carcinoma: A clinicopathologic problem. Am J Clin Pathol 47:767-780, 1967. 13. Okata N, Ota J, Sato K, Kitano Y: Metastasizing eccrine sweat gland carcinoma. Arch Dermatol 120:768-769, 1984.

A case of multicentric reticulohistiocytosis with thyroid involvement Lorraine G. Finelli, D.O., Laura K. Tenner, M.D., John L. Ratz, M.D., and Bruce D. Long, M.D. Cleveland, OH A case of multicentric reticulohistiocytosis with thyroid involvement is reported. This systemic condition has an unknown cause and is manifested by the development o f nodules containing an infiltrate of characteristic histiocytic and multinucleated giant cells in the synovium, skin, subcutaneous tissues, and occasionally bone or other tissues. (J AM ACAD DERMATOL 15:1097-1100, 1986.)

Besides the term multicentric reticulohistiocytosis, first suggested by Goltz and Laymon in From the Department of Dermatology, Cleveland Clinic Foundation. No reprints available.

1954, this disorder has been called lipoid dermatoarthritis, lipoid rheumatism, reticulohistiocytoma, giant cell histiocytomatosis, and others. In i969 Barrow and Holubar ~ identified thirtythree cases of multicentrie reticulohistiocytosis in 1097