 |
|
Intralesional Cisplatin for the Treatment of Cutaneous B-Cell Lymphoma
Werner Kempf, MD;
Reinhardn Dummer, MD;
Monika Hess Schmid, MD;
Tanja Fritz, MD;
Brunello Wüthrich, MD;
Guenter Burg, MD
Department of Dermatology, Zurich University Hospital, Zurich, Switzerland
Arch Dermatol. 1998;134:1343-1345.
REPORT OF A CASE
A 56-year-old white woman presented with a solid erythematous nodule on her scalp that had developed 6 years earlier. She denied having a fever, losing weight, or sweating during the night. Her medical history was notable for epilepsy, which was adequately controlled with phenothiazine and chlorpromazine therapy. When a solitary nodule first appeared on the patient's head 6 years earlier, a biopsy specimen revealed nodular, dense B-cell infiltrates without blasts, nuclear atypias, or mitoses. Therefore, the lesion had been regarded clinically and histologically as a B-cell pseudolymphoma. The patient was subsequently treated with potent topical corticosteroid creams and local psoralen–UV-A, but within 2 years the preexisting nodule became larger and 2 further nodules appeared despite the therapy. After topical chemotherapy using carbomustine and topical corticosteroids, the patient had a partial response consisting of a reduction in tumor size, but the tumors recurred after a few months.
The results of a physical examination showed that she had 4 dense, erythematous, smooth nodules with a median size of 3 cm on the frontal and parietal areas of her scalp accompanied by alopecia (Figure 1). No enlarged lymph nodes were palpable.
|
|
|
|
Figure 1. Erythematous nodule of cutaneous B-cell lymphoma on the parietal area of the patient's scalp before treatment with intralesional cisplatin gel.
|
|
|
The results of a histopathological examination of the nodules revealed a dense nodular infiltrate extending throughout all dermal layers into the subcutaneous fat, exhibiting a follicular pattern that was separated from the epidermis by an uninvolved grenz zone. Cytomorphologically germinal center–derived cells with pale cytoplasm, pleomorphic nuclei, and a few atypical mitoses were found (Figure 2). The cells stained for B-cell markers including CD20 (Figure 2), CD79a, and proliferation-associated Ki-67 marker. Immunohistochemical staining for  and  light chains of immunoglobulins showed a restricted reactivity of the tumor cells for the immunoglobulin light chain. Genotyping with amplification of immunoglobulin-heavy specific regions using a polymerase chain reaction did not reveal a monoclonal B-cell population. A chest x-ray film, an abdominal ultrasonogram, and a computed tomographic head scan showed no abnormal findings. In addition, examination of peripheral blood and a bone marrow biopsy specimen showed no evidence of an extracutaneous lymphoma.
|
|
|
|
Figure 2. Cutaneous B-cell lymphoma. Left, Centroblasts, centrocytes, and small B-lymphocytes (hematoxylin-eosin, original magnification x640). Right, Immunohistochemical detection of CD20 expression (alkaline phosphatase antialkaline phosphatase complex, original magnification x600).
|
|
|
Based on histopathological and clinical findings, the diagnosis of a follicle center cell lymphoma of the head and neck, a subtype of a primary cutaneous B-cell lymphoma, was made.
THERAPEUTIC CHALLENGE
Because the patient refused radiotherapy and excision of the tumoral nodules, and because other therapeutic approaches such as topical corticosteroids, psoralen–UV-A, and carbomustine had failed to resolve the tumors, an alternate local treatment was needed.
SOLUTION
Local chemotherapy has been used as a therapeutic approach for various skin tumors. Experimental and early clinical trials indicated that intratumoral-injected cisplatin in a collagen-epinephrine gel could be a new potent local chemotherapy for various tumors, especially for those on the head and neck. Based on experience with patients who had other head and neck tumors, we injected 0.5 to 1.0 mL of 4 mg/mL of cisplatin with 0.1 mg/mL of epinephrine in a collagen-containing gel (IntraDose, Matrix Pharmaceutical Inc, Fremont, Calif) once per week into 2 of the 4 tumoral nodules over a period of 5 weeks, with a total cumulative dose of 16 mg per nodule. After the third injection, the tumoral lesions became demarcated and necrotic (Figure 3). Two months after initiation of therapy, the necrotic tumor mass could be removed using curettage without surgical intervention or anesthesia. The resulting erosive wound area healed rapidly, leaving a hairless scar (Figure 4). After 5 months, no clinical recurrence of the lymphoproliferative infiltrates could be detected. However, untreated lesions continued to grow.
|
|
|
|
Figure 3. Necrosis in the area of treated nodules after the patient received the third injection of intralesionally applied cisplatin gel.
|
|
|
|
|
|
|
Figure 4. Reepithelialized area without recurrences of cutaneous B-cell lymphoma at 5 months' follow-up.
|
|
|
During the cisplatin-gel injection, the patient reported feeling pain at the injection site and slight nausea. After the third injection, swelling and an erythematous flush developed on the same side of her face after 1 hour, which persisted for many hours. The results of serologic investigation and prick or scratch tests did not reveal a sensitization against collagen and epinephrine as components of the gel, although cisplatin was not tested because of its direct toxic effect. Pretreatment with oral antihistamines did not prevent a similar reaction after the fourth and fifth injections.
COMMENT
Follicle center cell lymphoma is the most common subtype of primary cutaneous B-cell lymphoma and is typically located on the head and neck.1-3 Whereas a more aggressive variant located on the lower legs has been reported, most cases of cutaneous B-cell lymphoma are usually confined to the skin for many years and show a favorable prognosis despite the tendency to recur after treatment.3-4
Because primary cutaneous B-cell lymphoma is a rare disease, there are no generally accepted standards for its treatment. Excision and/or radiotherapy are the primary therapeutic modalities, but successful treatment with topical or intralesional corticosteroids as well as local chemotherapy has been reported.5-6 Once the tumor has spread to extracutaneous sites, systemic chemotherapy is often necessary.3, 7
Cisplatin is used as a systemic chemotherapeutic drug either alone or in combination with other drugs in a regimen to treat several malignant neoplasms, such as testicular cancer, head and neck cancer, and other solid tumors.8 It exhibits cytotoxic properties because of the cross-linking of DNA molecules, resulting in a breakdown of DNA synthesis and induction of tumor cell apoptosis.8-9
Cisplatin gel is a 3-component gel system consisting of a bovine collagen gel base containing cisplatin in a concentration of 4 mg/mL as the active cytotoxic drug and epinephrine, 0.1 mg/mL, to avoid rapid diffusion of cisplatin from the tumor and into the circulation. This composition results in an intratumoral concentration of cisplatin that is 10-fold greater than that after systemic intravenous injection of the drug. Veterinary data have demonstrated that intratumorally injected cisplatin gel is effective for the treatment of various tumors, including primary and secondary hepatic cancers and accessible head and neck cancer.10-11 Experimental data of ongoing studies in the treatment of human neoplasms, such as primary and secondary hepatic cancers and accessible head and neck cancer, reveal complete or partial response in 30% and 60% of treated lesions, respectively. Treatment of cutaneous lymphoma with intralesionally administered cisplatin has not been reported before. The therapeutic effect can be expected after the third to fourth injection with formation of necrosis and subsequent demarcation of the tumoral lesion. The most common adverse effects of cisplatin injections include acute pain at the injection site during injection and nausea. Swelling and erythematous flushing as observed in our patient have rarely been reported (data from Martrix database, accessed 1997) and seem not to be due to an allergic reaction.
Intratumoral injection of cisplatin-epinephrine gel may be an alternative therapeutic approach for the treatment of primary cutaneous B-cell lymphoma.
AUTHOR INFORMATION
Presented as a scientific poster at the European Society for Dermatolocial Research and the European Organization for Research and Treatment of Cancer meeting for Cutaneous Malignant Lymphomas, Berlin, Germany, September 1997, and published as an abstract in the Journal of Investigative Dermatology (1997;109:495).
Dr Kempf was a dermatology resident at the time the study was done.
REFERENCES
| |
1. Burg G, Hess Schmid M, Küng E, Dommann S, Dummer R. Semimalignant (pseudolymphomatous) cutaneous B-cell lymphomas. Dermatol Clin. 1994;12:399-407.
WEB OF SCIENCE
| PUBMED
2. Garcia CF, Weiss LM, Warnke RA, Wood GS. Cutaneous follicular lymphoma. Am J Surg Pathol. 1986;10:454-463.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
3. Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood. 1997;90:354-371.
FREE FULL TEXT
4. Santucci M, Pimpinelli N, Arganini L. Primary cutaneous B-cell lymphoma: a unique type of low grade lymphoma. Cancer. 1991;67:2311-2326.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
5. Zemtsov A, Camisa C. Treatment of primary cutaneous B cell lymphoma with local radiotherapy. Cutis. 1990;45:435-438.
WEB OF SCIENCE
| PUBMED
6. Watsky KL, Longley BJ, Dvoretzky I. Primary cutaneous B-cell lymphoma: diagnosis, treatment, and prognosis. J Dermatol Surg Oncol. 1992;18:951-954.
WEB OF SCIENCE
| PUBMED
7. Joly P, Charlotte F, Leibowitch M, et al. Cutaneous lymphomas other than mycosis fungoides: follow-up study of 52 patients. J Clin Oncol. 1991;9:1994-2001.
FREE FULL TEXT
8. Rozencweig M, Von Hoff DD, Slavik M, Muggia FM. Cis–diamminedichloroplatinum (II): a new anticancer drug. Ann Intern Med. 1977;86:803-812.
FREE FULL TEXT
9. Zhao R, Rabo YB, Egyhazi S, et al. Apoptosis and c-jun induction by cisplatin in a human melanoma cell line and a drug-resistant daughter cell line. Anticancer Drugs. 1995;6:657-668.
PUBMED
10. Orenberg EK, Luck EE, Brown DM, Kitchell BE. Implant delivery system: intralesional delivery of chemotherapeutic agents for treatment of spontaneous skin tumors in veterinary patients. Clin Dermatol. 1991;9:561-568.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
11. Kitchell BE, Brown DM, Luck EE, Woods LL, Orenberg EK, Bloch DA. Intralesional implant for treatment of primary oral malignant melanoma in dogs. J Am Vet Med Assoc. 1994;204:229-236.
WEB OF SCIENCE
| PUBMED
SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: LYNN A. CORNELIUS, MD; JOHN STARR, MD
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas
Senff et al.
Blood 2008;112:1600-1609.
ABSTRACT
| FULL TEXT
The Role of Intratumoral Therapy With Cisplatin/Epinephrine Injectable Gel in the Management of Advanced Squamous Cell Carcinoma of the Head and Neck
Wenig et al.
Arch Otolaryngol Head Neck Surg 2002;128:880-885.
ABSTRACT
| FULL TEXT
Intralesional Therapy With Anti-CD20 Monoclonal Antibody Rituximab in Primary Cutaneous B-Cell Lymphoma
Heinzerling et al.
Arch Dermatol 2000;136:374-378.
ABSTRACT
| FULL TEXT
|
