Letters to the Editor

Dermatofibrosarcoma Protuberans: Early Recognition and Treatment

TO THE EDITOR: Dermatofibrosarcoma protuberans (DFSP) is an uncommon, but not rare, aggressive soft tissue sarcoma arising in the dermis, with a high recurrence rate and a low metastatic potential. The tumor usually presents in young to middle-aged adults (20 to 50 years of age) and is rare in childhood or at birth. Men are affected slightly more frequently than women (57 percent versus 43 percent).¹

My interest in this subject was initiated after seeing two cases in my office within the past year. Accurate recognition and referral for appropriate initial treatment is essential to increase the patient's chance of a successful excision and avoidance of recurrence.

FIGURE 1. Dermatofibrosarcoma protuberans tumor. The radially oriented spindle cells extend into subcutaneous fat resulting in the characteristic "honeycomb" entrapment of the fat.

Clinically, patients with DFSP present initially with an asymptomatic nodule or plaque ranging in size from a few millimeters to more than 20 cm, most commonly located on the trunk and proximal extremities.² The tumors may be bluish, red-brown or flesh-colored and slowly infiltrate the surrounding tissues, eventually forming protuberant nodules and causing discomfort. If left untreated, the tumor will enlarge, protrude through the skin and ulcerate. The differential diagnoses include dermatofibroma, keloid, Kaposi's sarcoma and metastatic carcinoma.

Diagnosis is confirmed through clinical evaluation in conjunction with histopathologic assessment of the lesion. Histologically, DFSP is a dermal tumor composed mainly of spindle cells that are radially oriented in a storiform or cartwheel pattern. Microscopic extension into subcutaneous fat with "honeycomb" entrapment of fat is characteristic. Mitoses are rare.³ A punch biopsy of the patient's lesion shows the dermal spindle cell tumor that infiltrates the subcutaneous fat causing "honeycomb" entrapment (see the accompanying figure). The dermal and subcutaneous infiltrates can extend well away from the primary mass and are responsible for the high recurrence rates following inadequate primary resection.

Surgical excision using wide margin resection or Mohs micrographic surgery (MMS) is the mainstay of treatment for patients with DFSP. Radiotherapy and chemotherapy have a limited role and are usually reserved for metastatic and recurrent disease. Referring the patient for the appropriate initial operative procedure is the main prognostic factor. Patients who underwent primary DFSP excision with undefined or conservative margins had an average recurrence rate of 43 percent; in another study, patients who underwent surgical excision with a wide 5 cm resection margin had a recurrence rate of zero percent.^4,5 The literature reports that DFSP lesions treated with MMS had an average recurrence rate of 1.6 percent.⁴ The consensus is that DFSP can be treated by MMS or surgical resection using at least 3 cm excisional margins. The location of the lesion and cosmetic outcome can best determine the procedure to use.

DFSP is an entity that most family physicians will see during their career. The clinical findings can be easily confused with other skin disorders, contributing to delayed and inappropriate management. Early and accurate recognition, along with appropriate initial treatment, ensures the best outcome and prognosis for the patient.

SEAN J. MURPHY, D.O.
Flight Surgeon
U.S. Naval Academy
Annapolis, MD 21401

REFERENCES

1. Bendix-Hansen K, Myhre-Jensen O, Kaae S. Dermatofibrosarcoma protuberans. A clinico-pathological study of nineteen cases and review of world literature. Scand J Plast Reconstr Surg 1983; 17:247-52.
2. Garcia C, Clark RE, Buchanan M. Dermatofibrosarcoma protuberans. Int J Dermatol 1996;35: 867-71.
3. Lopes JM, Paiva ME. Dermatofibrosarcoma protuberans: a histological and ultrastructural study of 11 cases with emphasis on the study of recurrences and histogenesis. Pathol Res Pract 1991;187:806-13.
4. Gloster HM Jr, Harris KR, Roenigk RK. A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans. J Am Acad Dermatol 1996; 35:82-7.
5. Arnaud EJ, Perrault M, Revol M, Servant JM, Banzet P. Surgical treatment of dermatofibrosarcoma protuberans. Plast Reconstr Surg 1997;100: 884-95.

Possible Ticlopidine-Induced Cholestatic Jaundice

TO THE EDITOR: Ticlopidine (Ticlid) is an effective platelet anti-aggregate used in the prevention of ischemic cerebral and coronary events.^1-3 Recently, it has also been used in the prevention of coronary stent occlusion.⁴ The most common adverse effects are diarrhea (20 percent) and dyspepsia (12 percent). Neutropenia is the most serious side effect (1 to 2 percent).^1-3,5 Liver abnormalities have been reported in 4.4 percent of patients.^2,5

In a MEDLINE search, we found 39 case reports concerning 46 patients who developed liver disturbances and jaundice while taking ticlopidine. We present a case report of ticlopidine-induced cholestatic jaundice that resolved after treatment with Ursolit (ursodeoxycholic acid).

A 67-year-old woman was prescribed ticlopidine for the primary prevention of heart disease after endoscopy revealed severe erosive gastritis and duodenitis caused by aspirin therapy. Omeprazole, 20 mg per day for one month, was added to the aspirin therapy. She remained asymptomatic for six months; however, heartburn returned, at which time aspirin was discontinued and ticlopidine was prescribed. The white blood cell count (WBC) and liver function tests were within normal limits before ticlopidine therapy was initiated.

After one month of therapy, malaise and severe pruritus developed. A deep jaundice (total bilirubin: 8.05 mg per dL; range 0.00 to 1.30 [138 µmol per L; range: 1.70 to 25.00]) and severe hepatocellular and cholestatic abnormalities appeared.

Other laboratory values included total alkaline phosphatase, 983 U per L (range: 30 to 140); alanine aminotransferase, 490 U per L (range: 1 to 40); aspartate aminotransferase, 244 U per L (range: 1 to 40) and gamma-glutamyltransferase, 338 U per L (range: 8 to 50).

A wide laboratory evaluation revealed the WBC, prothrombin time and partial thromboplastin time to be within normal limits. Comprehensive serology and immunology tests were negative, and ceruloplasmin, urinary copper and thyroid-stimulating hormone levels were within normal limits. Ultrasonography was normal.

Ticlopidine was discontinued, with no laboratory improvement evident after four weeks. The patient did not consent to a proposed liver biopsy. Because of severe pruritus and deep jaundice, treatment with Ursolit was initiated, with improvement soon thereafter. Bilirubin blood level and liver function tests reached normal values after 10 months of therapy. Now, 10 months after discontinuing treatment with Ursolit, the patient feels well and the laboratory tests continue to be within normal limits.

Ticlopidine is an adenosine diphosphate receptor-PT₂ inhibitor of platelet aggregation^4,5 that is widely used in the prevention of ischemic cerebral or coronary events, peripheral vascular disease^1-3,5 and coronary stent occlusion.⁴ It is hepatically metabolized and has an unknown mechanism of hepatotoxicity.⁵ It presents most often as an impairment in liver function tests with cholestasis that appears three to 12 weeks after initiation of therapy. One report³ indicated a higher prevalence in the elderly; the common dose was 250 mg twice daily. In some cases, cholelithiasis was present. In our case, no history of previous disease or intercurrent therapy was found. Laboratory tests were within normal limits one week before the start of therapy. Because of severe complaints, treatment with Ursolit, a hydrophilic bile acid used to treat cholestatic liver disorders,⁶ was initiated. Recovery was protracted.

A clear temporal relationship between the initiation of the drug therapy with ticlopidine and onset of liver abnormalities was found. We believe that our patient represents a case of ticlopidine-induced hepatotoxicity.

DOV WENGROWER, M.D.
Dept. of Gastroenterology
Hadassah University Hospital
POB 12000
Jerusalem, Israel 91120

REFERENCES

1. Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989;321:501-7.
2. Gent M, Blakely JA, Easton JD, Ellis DJ, Hachinski VC, Harbison JW, et al. The Canadian American Ticlopdine Study (CATS) in thromboembolic stroke. Lancet 1989;1:1215-20.
3. Iqbal M, Goenka P, Young MF, Thomas E, Borthwick TR. Ticlopidine-induced cholestatic hepatitis: report of three cases and review of the literature. Dig Dis Sci 1998;43:2223-6.
4. Leon MB, Bain DS, Pompa JJ, Gordon PC, Cutlip De, Ho KK, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. N Engl J Med 1998;339:1665-71.
5. McTavish D, Faulds D, Goa KL. Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders. Drugs 1990;40:238-59.
6. Poupon R, Poupon RE. Ursodeoxycholic acid therapy of chronic cholestatic conditions in adults and children. Pharmacol Ther 1995;66:1-15.

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Correction*

The article titled "The Preparticipation Athletic Evaluation" (May 1, 2000, page 2683) contained several errors. The legend to Figure 1 contained two errors; the ST elevations in leads I, V4, V5 and V6 should have been referred to as lateral leads, rather than anterior leads, and the T waves in V2 and V3 should have been referred to as biphasic, rather than inverted. In the first full paragraph on page 2687, the word "echocardiography" was erroneously abbreviated as ECG. Table 2 contained an incorrect reference to Figure 1. The table should have referred readers to the Appendix following the article, on page 2696. The corrected figure and table are reprinted above.

*These corrections have been made to the online version of AFP. The links above will take you to the corrected items, which remain part of the online issues in which they were originally published.

Send letters to Jay Siwek, M.D., Editor, American Family Physician, 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672; fax:913-906-6080; e-mail: afplet@aafp.org. Please include your complete address, telephone number and fax number. Letters should be double-spaced, fewer than 500 words and limited to one table or figure and six references. Please submit a word count. Letters submitted for publication in AFP must not be submitted to any other publication. Possible conflicts of interest must be disclosed at time of submission. Submission of a letter constitutes transfer of copyright to the American Academy of Family Physicians. The editors may edit letters to meet style and space requirements.

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