Mihn Sook Jue

Extramammary Paget Disease: Minimal Surgical Therapy

Background Extramammary Paget disease (EMPD) is an uncommon malignant neoplasm affecting apocrine gland-bearing skin which usually occurs in the anogenital area of patients older than 50 years. Although Mohs micrographic surgery (MMS) is recommended for the treatment of EMPD, wide local excision has also been performed by many other surgeons including dermatosurgeons. However, the extent of an adequate resection margin is still under debate. Objective The efficacy of minimal surgical therapy consisting of a wide excision combined with preoperative multiple scouting biopsies and postoperative topical imiquimod was investigated for the treatment of EMPD in Korean patients. Methods Between 2006 and 2012, 10 patients with primary EMPD were treated with wide surgical excision, with a surgical margin of less than 2.5 cm. Multiple preoperative scouting biopsies and postoperative topical imiquimod were also performed to delineate the lesional boundaries and to reduce the recurrence rate. Results During the 6-year follow-up period, complications and recurrences were not observed. Conclusion Minimal surgical therapy may be an effective alternative when MMS is unavailable.

Treatment for Refractory Pruritus Using Oral Aprepitant

Dear Editor: Chronic pruritus is difficult to treat and severely affects patients quality of life and psychological well-being. Substance P (SP) is an important mediator in the induction and maintenance of pruritus, and therefore represents a promising target for antipruritic treatment. Aprepitant is an oral neurokinin-1 receptor (NK-1R) antagonist, which acts by inhibiting the binding of the NK-1R with the SP ligand in the skin and central nervous system1,2. A 79-year-old man presented with refractory pruritus that had been resistant to local application of corticosteroid, standard systemic therapies such as antihistamine, cyclosporine, gabapentin and tricyclic antidepressant, and phototherapy. The origin of pruritus was unclear despite extensive laboratory and radiological investigation. Histopathological examination of a biopsy taken from the lower back showed superficial psoriasiform dermatitis with spongiosis and parakeratosis. He complained that he could not sleep for more than 1 hour because of the pruritus. After stopping antipruritic treatment for 3 weeks, we administered 125 mg of aprepitant on day 1 and 80 mg on day 2, 3 and 4 at the same time of day. Before treatment, visual analogue scale (VAS) score was 8/10 and Dermatologic Life Quality Index (DLQI) score was 24/30. After 24 hours from first administration, these values reduced to 4 and 16, respectively. He mentioned that pruritus was reduced significantly and he could consistently sleep for more than 4 hours. After 6 weeks, VAS and DLQI scores were 1 and 8 (Table 1), and his cutaneous lesions were much improved (Fig. 1). He was completely satisfied with deep sleep and no adverse effects were observed. Fig. 1 (A) Multiple excoriated papules and linear excoriations on the trunk before treatment. (B) At the 6-week follow-up, the excoriated papules and linear excoriations appear to be significantly improved. Table 1 Pruritus scores based on a visual analogue scale (VAS) and quality of life based on the Dermatology Life Quality Index (DLQI) before and after treatment with aprepitant Aprepitant was developed and approved in 2003 for the prevention of chemotherapy-induced emesis and is usually administered for three days only (125 mg, 80 mg, 80 mg)1,2. Several studies have been performed to investigate the antipruritic effect of aprepitant. Although different regimens of aprepitant were used in previous studies, the results generally showed a significant reduction of pruritus without relevant side effects2,3,4,5. In this case, we administered 125 mg of aprepitant on day 1, and 80 mg on day 2, 3, and 4. Twenty-four hours after the first administration, the patient mentioned that his pruritus was significantly reduced (VAS 8 to 4). Other studies also demonstrated immediate antipruritic effect of aprepitant within 1 to 7 days after first administration3,4,5, and the median time to recurrence was 7 weeks from the first dose3. In our case, the antipruritic effect continued for 6 weeks. These results suggest that aprepitant has a long-lasting action. In vitro data have shown that aprepitant slowly dissociates from the human NK-1R and, as a competitive antagonist, it might also be a pseudo-irreversible antagonist3. Later, pruritus was aggravated temporarily, but it was easily relieved with standard antipruritic treatments. To date, he maintains improved state of pruritus. To our knowledge, this is the first report of the antipruritic effect of aprepitant in Asia. This case supports previous reports of a significant antipruritic effect of aprepitant, especially in Asians, which is a good alternative treatment modality in chronic pruritus. Further studies are needed to determine a proper regimen and to prove the exact efficacy of aprepitant.

Blue Toe Syndrome as an Early Sign of Disseminated Intravascular Coagulation.

Dear Editor: Blue toe syndrome (BTS) is often described as painful digits with blue or purple discoloration without direct trauma1. Also it can lead to the amputation of toes and feet and be life threatening. Atheromatous embolism caused by vascular wall injuries from invasive percutaneous procedures or from anticoagulant or fibrinolytic therapy is reported as a common cause of BTS2. However, other causes of decreased blood flow are thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, and other vascular obstruction2. The conditions which lead to thrombotic state such as disseminated intravascular coagulation (DIC) can also give rise to BTS. Herein, we report a rare case of BTS that occurred as an early sign of DIC. In our institute, a 69-year-old male complained of non-palpable bluish discoloration on both feet after he was admitted to the ICU ward due to pneumonia (Fig. 1). The physical examination demonstrates symmetric color change with petechiae that had lasted 1 month. The toes felt cold, and the sensation of toes was uncheckable because of his semi-coma status. Also the patient has been treated for pneumonia with history of diabetes mellitus, hypertension, and cerebral infarct. On histological examination from his foot, ischemic necrosis of epidermis and tons of red blood cell extravasation were found (Fig. 2A, B). Also, there were eosinophilic fibrinoid thrombi in the medium- sized vessels and leukocytoclasis (Fig. 2C). The laboratory results were as follows: white blood cell 28,470/mm3, hemoglobin 9.4 g/dl, platelet 37,000/mm3, prothrombin time/activated partial thromboplastin time 18.4/91.7 s, fibrinogen 71 mg/dl, D-dimer 3.75 mg/L. Hence, we could confirm that the causative disease might be DIC. After then, we obtained the result of multi drug resistant acinetobacter baumannii bacteremia from the blood culture. Gram stain and bacterial culture of the skin tissue were not conducted. We concluded that DIC resulted from severe infectious bacteremia. Henceforward, the patient was treated with vancomycin and conservative care for DIC. However, the patient died after 1 month. The possibility of purpura fulminans was ruled out because the patients lesion was limited to the toes. Fig. 1 Blue to purple discoloration with petechiae on the right foot. Fig. 2 (A) Scanning view (H&E, ×40). (B) Ischemic necrosis of epidermis, and red blood cell extravasation (H&E, ×200)

Auricular composite chondrocutaneous grafts in the repair of nasal alar rim defects.

Dear Editor: An 82-year-old man presented with a grayish-black papule on the right ala of the nose that had been there for 3 to 4 years, and which bled occasionally. Physical examination revealed that the size of the papule was 0.5×0.5 cm. The patient had no family history of skin cancer; he had a history of heavy cigarette smoking. We suspected basal cell carcinoma and performed a 2-mm punch biopsy. The results of the pathologic examination of the specimen confirmed the diagnosis of basal cell carcinoma. Before the surgery, we ensured that he stopped cigarette smoking to allow better survival of the graft. The tumor was widely excised with a 2-mm surgical margin, resulting in a 0.9×0.8 cm full-thickness defect (Fig. 1A). The defect was reconstructed by using a composite chondrocutaneous graft harvested from the antitragus of the right ear (Fig. 1B). The graft was prepared in such a way that it was approximately 20% larger than the defect in order to compensate for the natural contraction of the graft. The donor site was closed primarily, and after hemostasis of the recipient bed, the defect was repaired with the composite skin graft (Fig. 1C). To lower the metabolic demand, an ice pack was applied to the recipient site postoperatively for surface cooling. At a 5-month postoperative follow-up, desirable aesthetic and functional results were observed (Fig. 2). The patient agreed publication of his case. Fig. 1 (A) Full-thickness defect of the nasal ala after tumor excision. (B) Composite graft designed over the donor site

Fibro-Osseous Pseudotumor of the Digit: A Diagnostic Pitfall of Extraskeletal Osteosarcoma

Dear Editor: Fibro-osseous pseudotumor of the digit (FOPD) is a rare, biphasic ossifying tumor in young patient, characterized by osteoid formation and fibroblastic proliferation1. There are some tumors showing heterotopic ossification: myositis ossificans (MO), ossifying plexiform tumor2, acral angioosteoma cutis3 and extraskeletal osteosarcoma (EO). However, if it developed in an old-aged patient with cellular atypism, physician has to consider an overdiagnosis of EO to prevent from unnecessary amputation of the digit4. Herein, we report a patient with FOPD that can lead to the mistaken diagnosis of EO and others. A 68-year-old male patient presented to the clinic with a tender, hard, half dome-shaped subcutaneous mass on the palmar side of left thumb (Fig. 1). The mass was 0.9 cm in diameter and had a duration of 3 months. There has been no history of trauma and infection. Also, he is a right-handed person. Other medical history is diabetic mellitus for about a decade. We took an incisional biopsy from the lesion and removed it totally. Histologically, at low power view, there are compact hyperkeratosis, epidermal hyperplasia and fusion of rete ridge in the epidermis. This mass shows no connection to the epidermis and bony structure (Fig. 2A). Moreover, irregular shaped osteoid formation surrounded by fibrotic band is observed with trabecular margin and calcified foci in subcutis layer (Fig. 2B). At high power field, osteoblast and multi-nucleated osteoclast are seen around osteoid portion. And a few of mitotic cells were detected (Fig. 2C). Biphasic immature pattern of spindle cellular portion and bony portion were shown chaotically at the same field. Also red blood cells extravasate from the capillary vessels. A part of cells has an irregular size, morphology and atypical nucleus (Fig. 2D). But we can exclude EO despite of these atypical features. Because overall cellular atypism is not severe and cellular density is not as high as in EO. After then, the patient stayed well without recurrence during follow-up for 6 months. Fig. 1 Painful, skin-colored, solitary mass on the left thumb. (A) Lateral view, (B) palmar side view. Fig. 2 (A) Scanning view demonstrating the subcutaneous trabecular mass (H&E, ×1), (B) osteoid formation surrounded by fibrotic band with trabecular margin and calcified foci (H&E, ×40), (C) multi-nucleated osteoclast (black arrow) ... The most confoundable diagnosis would be a MO. Also, some author asserts that FOPD could be a superficial and distal variant of MO5. But, MO usually has a history of trauma, occurs on the deeper aspect of proximal soft tissue, and histopathologically shows a typical zoning phenomenon1. And ossifying plexiforn tumor may be clinically similar to FOPD in its propensity to develop on a distal finger. But the plexiform pattern of fibroblastic proliferation and osteoid formation is different from FOPD2. Also acral angioosteoma cutis can looks like FOPD given the ossification of acral soft tissue. But this tumor obviously has a portion of dilated capillary network3. Above all, the most important differential diagnosis is EO to avoid aggressive surgery4, especially when it accompany with a history of short duration, painful symptom and old age patient. So it is histologically essential to find and check malignant cells with pleomorphism. In conclusion, FOPD is a rare ossifying tumor which can lead a mistaken diagnosis of EO. Our case emphasizes the need to detect these differential diagnoses in patients with tumor occurring on the digit with ossification.