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VOLUME 22 NUMBER 5 PART 2 I II

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MAY 1990

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Metastatic basal cell carcinoma: Response to chemotherapy Margaret M. Bason, MD, a Jane M. Grant-Kels, MD, b and Mithlesh GoviI, M D c

Hartford, Farmington, and New London, Connecticut Basal cell carcinoma is a common cutaneous neoplasm that rarely metastasizes. Unfortunately, there is little effective treatment available when metastasis does occur. Therefore potentially promising therapies for metastatic basal cell carcinoma should be reported. We report a case of basal cell carcinoma metastatic to bone, bone marrow, and the pleural cavity in a 51-year-old woman who showed a striking, albeit brief, response to treatment with a combination of cisplatin, Neomycin, methotrexate, and 5-fluorouracil, (J Ant AeAD DERMATOL 1990;22:905-8.)

The first case of metastatic basal cell carcinoma was reported in 1894.1 Since then, fewer than 200 cases have been recorded} Once the tumor has metastasized beyond the regional lymph nodes, it is usually fatal, with a reported mean survival time of 10 to 14 months) W e report a case of extensive metastatic disease in which an excellent response was achieved with chemotherapy. After a 3-month remission, however, a recurrence of the tumor was resistant to therapy and resulted in the patient's death.

CASE REPORT In May 1983 a 51-year-old white woman was seen with a 2-week history of shortness of breath during minimal exertion. A large, ulcerated, fungating lesion on the left side of the neck had been present for 18 to 20 years and had rapidly increased in size during the last 2 years; however, medical attention had not been sought. The patient also noted pain in the right hip and lower lumbar region of 6 to 8 weeks' duration. Initially, she refused complete evaluation of the lesion and was admitted for anemia. She

From the Department of Medicine, Hartford Hospital,a the University of Connecticut School of Medicine, Farmington, b and the University of Connecticut Health Center and Lawrence and Memorial Hospital, New London.e Reprint requests: Jane M. Grant-Kels, MD, University of Connecticut Health Center, Division of Dermatology, L 2060, Farmington, CT 06032, 16/4/10316

received a transfusion of 3 units of blood, and her dyspnea improved. Two weeks later the patient returned for complete evaluation of the lesion. On physical examination the patient appeared cachectic and pale. She had a large mass occupying the entire left side of the neck and extending to the left breast (Fig. 1). There was an ulcerated central area with nodular, pearly and telangieetatic, cauliflower-like excrescences at the periphery. Tumor covered the trachea but did not expose it. Complete paralysis of the left side of the larynx was present as a result of recurrent laryngeal nerve involvement. Chest examination revealed dullness of percussion at the base of the left lung with absent breath sounds and scattered tales. Several palpable lymph nodes were found in the left axiIla. A biopsy specimen demonstrated aggregates of basaloid cells with large hyperchromatic nuclei, scant cytoplasm, palisading of the peripheral nuclei, and focal stroreal retraction (Figs. 2 and 3). Foci of squamous cell differentiation were present (Fig. 4). Results of laboratory studies revealed anemia (hematocrit 28.2%), leukoerythroblastic features on peripheral smear, and elevated levels of alkaline phosphatase (410 U / L ) and lactate dehydrogenase (427 U/L). X-ray films showed widespread osteolysis of vertebrae, ribs, clavicles, femurs, and pelvis, and a left pleural effusion. A bone scan revealed multiple metastatic lesions, and a biopsy specimen of bone marrow verified infiltration of basal cell carcinoma (Fig. 5). Liver and spleen scans were normal. The patient began a regimen of cisplatin, 20 mg/rn2/ day, given as an intravenous bolus from day 1 to day 5; 905

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Volume 22 Number 5, Part 2 May 1990 bleomycin, 15 U/day continuous infusion from day 3 to day 7; and methotrexate, 200 mg/m2/day, on days 14 and 21, with subsequent leucovorin rescue, 25 mg orally every 6 hours for 12 doses beginning 24 hours after methotrexate administration. There was a 2- to 3-week interval between courses of chemotherapy, and the dose of methotrexate was reduced by 50% after the initial dose because of a decreased creatinine clearance rate. After four courses of chemotherapy, the patient's regimen was switched from bleomycin to 5-fluorouracil, 500 mg/m2/ day for 5 days as a continuous infusion, because she had received the maximum allowable dose of bleomycin. The patient showed immediate, marked clinical improvement. A repeated chest x-ray filmin December 1983 revealed resolution of the pleural effusion. The left side of the neck was completely healed (Fig. 6). A biopsy specimen of bone marrow after five courses of chemotherapy revealed moderately hypercellular marrow with absence of tumor cells (Fig. 7). In Feburary 1984, after seven courses of chemotherapy, the patient's disease was in complete remission, and all treatment was discontinued. In May 1984 the patient was readmitted because of local recurrenceof her neck lesion. Biopsy specimens again revealed basal cell carcinoma. A repetition of the original chemotherapeutic regimen with cisplatin and 5-fluorouracil was reinstated; however, because of the patient's decreased creatinine clearance, methotrexate was not given. The patient showed little improvement, and she received an additional 6000 tad of radiation to the lesion, resulting in some shrinkage. Despite continuing chemotherapy, however, involvement of bone progressed. In January 1985 the patient had spinal cord compression of the upper thoracic and cervical spinal region as a result of direct extension of the neck lesion. Surgical decompression was performed, and additional radiation (3000 rad) to the spine and weekly methotrexate, 15 mg in-

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travenously, and monthly 5-fluorouracil were administered. In April 1985 the patient received additional chemotherapy with methotrexate, 50 mg intravenously, and, as before, a 5-day infusion of 5-fluorouracil. Despite therapy, the disease progressed with widespread recurrenceof metastatic bone lesions. In May 1985, 2 years after the patient's first hospital admission, she was readmitted and died 5 hours later. No autopsy was performed. DISCUSSION The incidence of metastatic basal cell carcinoma ranges from 0.0028% to 0.1% in large series. 4"6 Regional lymph nodes are the most frequent site of metastasis; lung and bone are the next most common.3, 7 In most cases there is a long history of extensive local disease because of the patient's neglect of the carcinoma or there is a history of multiple recurrences after treatment, s'11 There have been sporadic reports, however, of small, minimally invaSive basal cell carcinomas that have metastasized. 12 The histologic findings from our patient's original lesion demonstrated focal squamous differentiation, or the metatypical type of basal cell carcinoma (basosquamous carcinoma). The basosquamous histologic pattern is the most common type found in metastasizing basal cell carcinomas. 13-15 Some investigators believe that basosquamous carcinoma demonstrates more aggressive behavior and requires more extensive treatment than that usually administered for basal cell carcinoma. 9' 14,15 Othersl6 disagree with the classification basosquamous carcinoma because they postulate that it m a y represent squamous cell carcinoma and basal cell carcinoma

Fig. 1. Anterolateral view of large, ulcerated mass of left side of neck with nodular, pearly borders characteristic of basal cell carcinoma. Fig. 2. Photomicrograph of lesion demonstrates neoplasm consisting of aggregates of basaloid cells consistent with diagnosis of basal cell carcinoma. (Hematoxylin-eosin stain; • Fig. 3. Higher-power magnification reveals basaloid cells withlarge, hyperchromaticnuclei, scant cytoplasm, palisading of peripheral nuclei, and focal stromal retraction. (Hematoxylineosin stain; Xl00.) Fig. 4, Photomicrograph shows focal squamous eddies within basaloid neoplasm. (Hematoxylin-eosin stain; X400.) Fig. 5. Photomicrograph of bone marrow biopsy specimen reveals aggregates of basaloid cells infiltrating marrow, displacing normal marrow elements, and causing myelophthisis. (Hematoxylin-cosin stain; • 100.) Fig. 6. Anterior view of lesion healing with normal skin after chemotherapy. Fig. 7. Photomicrograph of bone marrow biopsy specimen after chemotherapy demonstrates absence of neoplastic basaloid cells. (Hematoxylin-eosin stain; • 100.)

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t h a t develop in close p r o x i m i t y and thus are found intermingled in the s a m e section. T o date, all t r e a t m e n t modalities designed to eradicate m e t a s t a t i c basal cell c a r c i n o m a have been disappointing. C o m p l e t e excision of the t u m o r is the m a i n goal. As in our patient, however, this is often not possible. T h e r e are a few isolated case reports of success with extensive surgical resection in lesions with bone a n d l y m p h node metastasisJ 7,18 Radiation t h e r a p y has been effective for palliation, b u t there are no reports o f survival benefits f r o m treatm e n t alone. 19 Because metastatic basal cell carcinoma is rare, t h e r e has not been extensive experience with chem o t h e r a p y , a n d therapeutic responses have been disappointing), 7, ~0 C h e m o t h e r a p e u t i c agents used included cyclophosphamide, etoposide, fluorouracil, methotrexate, cisplatin, N e o m y c i n , and doxorubicin. In t h e few reports of successfully treated patients, cisplatin has been effective with or without other agents. 2~ In combination with Neomycin and methotrexate, cisplatin m a y be a n effective agent in the t r e a t m e n t of m e t a s t a t i c basal cell carcinoma. REFERENCES 1. Beadles CF. Rodent ulcer. Trans Pathol Soc 1894; 45:17681. 2. von Domarus H, Stevens PJ, Metastatic basal cell carcinoma: report &five cases and review of 170 cases in the literature. J AM ACAD DERMATOL1984;10:1043-60. 3. Safai B, Good RA. Basal cell carcinoma with metastasis. Arch Pathol Lab Med 1977;101:327-31. 4. Smith JM, Iron GB. Metastatic basal cell carcinoma: review of the literature and report of three cases. Ann Plast Surg 1983;11:551-3. 5. Mikhail GR, Nims LP, Kelly AP Jr, et al. Metastatic basal ceil carcinoma. Arch Dermatol 1977;113:1261-9. 6. Paver K, Poyzer K, Burry N, et al. The incidence of basal cell carcinoma and their metastases in Australia and New Zealand. Aust J Dermatol 1973;14:53.

Journal of the American Academy of Dermatology 7. Costanza ME, Dayal Y, Binder S, et al. Metastatic basal cell carcinoma: review, report of case, and chemotherapy. Cancer 1974;34:230-5. 8. Amonette RA, Salasche SJ, ChesneyTM, etal. Metastatic basal cell carcinoma. J Dermatol Surg Oncol 1981;7:397400. 9. Bianchini R, Wolter M. Fatal outcome in a metatypical, giant, "horrifying" basal cell carcinoma. J Dermatol Surg Oncol 1987;13:556-7. 10. Coker DD, Elias EG, Viravathana T, et al. Chemotherapy for metastatic basal cell carcinoma. Arch Dermatol 1983; 119:44-50. 11. Icli F, Uluoglu O, Yalav E, et al. Basal cell carcinoma with lung metastases: a case report. J Surg Oncol 1986;33:5760. 12. Menz J, Sterrett G, Wall L. Metastatic basal cell carcinoma associated with a small primary tumour. Aust J Dermatol 1985;3:121-4. 13. Freeman RG. Histological consideration in the management of skin cancer. J Dermatol Surg 1976;2:215-9. 14. Farmer ER, Helwig EB. Metastatic basal cell carcinoma: a clinicopathological study of seventeen cases. Cancer 1980;46:748-57. 15. Borel DM. Cutaneous basosquamous carcinoma. Arch Pathol 1973;95:293-7. 16. Mehregan AH. Basal cell epithelioma. In: Mehregan AH, ed. Pinkus' guide to dermatohistopathology. 4th ed. Norwalk, Corm: Appleton-Century-Crofts, 1986:509-21. 17. Conley J, Sachs ME, Romo T, et al. Metastatic basal cell carcinoma of the head and neck. Otolaryngol Head Neck Surg 1985;4:78-85. 18. Scanlon EF, Volkmer DD, Oviedo MA, et al. Metastatic basal cell carcinoma. J Surg Oncol 1980;2:171-80. 19. Hartman R, Hartman S, Green N. Long-term survivalfollowing bony metastases from basal cell carcinoma. Arch Dermatol 1986;122:912-4. 20. Cieplinski W. Combination chemotherapy for the treatment of metastatic basal cell carcinoma of the scrotum: a case report. Clin Oncol 1984;10:267-72. 21. Dickie GJ, Pratt GR. Basal cell carcinoma of the skin responding completely to chemotherapy [Letter]. Arch Dermatol 1988;124:494. 22. Salem P, Hall SW, Benjamin RS, et al. Clinical phase I-II study of cis-dichlorodiatrfineplatinum(II) given by continuous 1V infusion. Cancer Treat Rep 1978;62:1553-5. 23. Wieman TJ, Shively EH, Woodcock TM. Responsiveness of metastatic basal cell carcinoma to chemotherapy. Cancer 1983;52:1583-5.

Metastatic basal cell carcinoma: response to chemotherapy.

Basal cell carcinoma is a common cutaneous neoplasm that rarely metastasizes. Unfortunately, there is little effective treatment available when metast...
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