Adam Ingraffea

Successful treatment of indeterminate cell histiocytosis with low‐dose methotrexate*

Dear Editor, A 65-year-old female with a history of hypothyroidism, irritable bowel syndrome, arthritis and hypertension was referred for evaluation of disseminated, pruritic lesions. The lesions first appeared 2 years previously on her left arm and recently had become more widespread. The patient had been treated with topical corticosteroids and oral antibiotics without any improvement. The patient presented no systemic symptoms. A total body skin examination was completed, revealing hundreds of firm, non-tender, pink papules ranging in size from 3–6 mm on her face, chest, abdomen, back and upper and lower extremities (Fig. 1a). Several of the lesions showed a crusted, necrotic center. No lesions were present on the buttocks or groin area. The scalp was clear of lesions. There was no lymphadenopathy. The differential diagnosis included pityriasis lichenoides et variolaformis acuta, lymphomatoid papulosis, disseminated granuloma annulare, xanthomas and leukemia cutis. Two punch biopsies from separate papules revealed an upper dermal infiltrate of cells with expanded pink cytoplasm and reniform to round nuclei with grooves (Fig. 1c). The histiocytic cells were surrounded by a lymphocytic infiltrate and eosinophils were not prominent. Immunohistological stains revealed that the histiocytic cells strongly expressed CD1a antigens and CD68. Expression of S100 was patchy. Langerin ⁄CD207 staining was negative in the dermal infiltrate, suggesting the absence of Birbeck granules (Supporting Information Fig. S1). Electron microscopy of multiple histiocytic cells showed irregularly-shaped nuclei, abundant cytoplasm and prominent mitochondria (Fig. 1d). Birbeck granules were absent upon electron microscopy. Extensive laboratory and imaging evaluation failed to reveal any underlying malignancy or systemic disease. Given the presentation, histopathological findings and electron microscopic examination, we confirmed the diagnosis of indeterminate cell histiocytosis (ICH). Despite this being a benign entity, the patient elected to begin treatment as the lesions on her face represented a significant cosmetic concern. Because the patient was unable to travel frequently, ultraviolet (UV) light therapy was not an option. The patient was started on methotrexate (12.5 mg weekly), which led to a complete clinical remission 2 months after beginning treatment (Fig. 1b). Following 5 months of treatment, the patient began to slowly taper off methotrexate. Within several weeks of decreasing her dose to 7.5 mg of methotrexate, new lesions began to develop at multiple sites. Her dose was escalated back up to 12.5 mg at this point. Indeterminate cell histiocytosis is an extremely rare disorder characterized by a proliferation of cells that have characteristics of both Langerhans cells and non-Langerhans cells. ICH was first defined in 1985 as a proliferation of cells positive for CD1a and S-100 protein, but lacking Birbeck granules. ICH has been described in both children and adults and

The Significance of Floaters in the Nicks of Mohs Frozen Sections

Floaters are pieces of tissue separated from the main excisional specimen during tissue harvesting or frozen section preparation during Mohs micrographic surgery (MMS). These tissue fragments, which may comprise tumor cells or normal tissue, are usually first noted during microscopic examination of the frozen section. A floater is identified as being a small island of tumor cells that appears to fit into or float within a scalpel nick. A floater is always an isolated finding and is never contiguous with other areas of tumor. There should not be any inflammation or fibrosis adjacent to the floater. Floaters of tumor cells, which typically appear at the periphery of frozen sections, may complicate the clearance of tumor during MMS by inducing the surgeon to take additional layers of tissue. Whether the presence floaters of tumor cells noted on frozen section examination represents true involvement of surgical margins with tumor has yet to be determined.

Use of a Preliminary Horizontal Mattress Suture on Scalp Biopsies to Achieve Rapid Hemostasis

Punch biopsies of the scalp can be stressful and sanguineous experiences for the clinician and patient. Even when a delay for epinephrine vasoconstriction is allowed, there is often a distressing amount of bleeding. The following technique is a simple and practical method to avoid excess scalp bleeding. As with any biopsy, adequate anesthesia is an important first step. Fourto 6-mm punch tools are commonly used for scalp biopsies. The trick to this technique is first to place a horizontal mattress suture, using a 3-0 or 4-0 nonabsorbable suture, around the area to be excised (Figure 1). The suture first enters the scalp at point 1 and travels subcutaneously to point 2. It then exits the skin and is reoriented. The needle re-enters the skin at point 3 and travels subcutaneously to point 4, where it exits. An assistant then draws the suture out and holds it out of the surgical field. Once the suture has been placed, a standard punch biopsy is done and the specimen collected. Immediately after the specimen is obtained, the suture is drawn tight and tied off, obtaining rapid and complete hemostasis. It is important to place the horizontal mattress wide enough to allow the punch tool to enter the area without cutting the suture. This technique may also be used for tongue biopsies.

Surgical Deroofing Procedure for the Treatment of an Auricular Pseudocyst.

The risk of perforating the internal table of the bone and the dura mater was considered during the trepanations, as these factors may determine the decrease in the thickness of the bone tables and its fibrosis, in addition to the density of the diploe. Furthermore, decreased vascularization results in a poor source of granulation tissue, which may cause the failure of this technique. The authors believe that these risks should be evaluated in advance using ultrasonography or magnetic resonance imaging.

Innovative use of a polarized magnifier and a smart phone: a microscope in your pocket.

The Dermlite Pro (3Gen Inc., San Juan Capistrano, CA) is a 910 polarized magnifier normally used for in vivo imaging of pigmented and nonpigmented skin lesions. A simple plastic sleeve allows the magnifier to be attached to an iPhone 4 or 4S for digital photographic dermoscopy. A novel use for the combination is for ex vivo imaging of Mohs frozen sections to obtain low-cost, high-quality histopathologic images. The combination is shown is Figure 1.

Time-Saving Tips for Processing Large, Fatty Mohs Specimens

Mohsmicrographic surgery (MMS) is normally reserved for areas of the head and neck, where tissue conservation is of paramount importance. For large tumors of the trunk (>2 cm in diameter) or for invasive tumors such as dermatofibrosarcoma protuberans (DFSP), MMS may also be the treatment of choice. For several reasons, fatty specimens are difficult and time consuming to process, so significant delays can be expected when large specimens containing a thick layer of subcutaneous fat are harvested and submitted for frozen section processing. Because fat freezes more slowly than the epidermis and dermis, more time must be allowed for the fat to solidify completely. By the time the fat has completely solidified, the dermis and epidermis may have become extremely hard, causing fracturing on the blade of the cryostat and damaging the tissue, which results in poor-quality slides.

Complications of Mohs Micrographic Surgery

The incidence of non-melanoma skin cancer is increasing rapidly in the United States. The rapid rise in the number of cases of NMSC has lead to an increasing demand for Mohs micrographic surgery. Along with this dramatic rise in the number of procedures being performed comes the risk of increased complications. However, with careful planning, good judgment, and proper techniques the risk of complications can be minimized. The primary goal of this chapter is to review the current recommendations and evidence for the prevention of the common complications in the setting of Mohs surgery. More serious, but thankfully rare, complications, as well as several recently described complications will also be reviewed.

Proteinuria in a patient using adalimumab for psoriasis

Dear Editor Adalimumab is a monoclonal antibody against tumor necrosis factor-α (TNF-α). It is currently Food and Drug Administration approved for the treatment of multiple conditions including psoriasis and psoriatic arthritis. We report the development of subnephrotic range proteinuria in an otherwise healthy 36-year-old man while taking adalimumab. A 36-year-old male patient with an 18-year history of psoriasis had been treated with different modalities including: topical corticosteroids, anthralin, acitretin, cyclosporine, psoralen plus ultraviolet A therapy and narrow-band ultraviolet B. He had not taken cyclosporine for 5 years. He had been treated with several biological agents including alefacept, etanercept and most recently with adalimumab, for the prior 18 months. He had had the greatest clinical response to adalimumab. Approximately 15 months after starting adalimumab he began to experience joint pain in his hands and fingers. His adalimumab dose was then increased to 40 mg weekly from 40 mg every other week. A routine screening urinalysis revealed greater than 300 mg of protein. The patient then underwent a 24-h urine collection which showed 1.34 g of protein, it also showed a creatinine clearance of 180 mL/min possibly due to urine over collection. His serum creatinine was 1.1, blood urea nitrogen was 12 and all other electrolytes were within normal limits. Cytoplasmic anti-neutrophil cytoplasmic antibody (cANCA), perinuclear ANCA, C3, C4 and antinuclear antibody levels were all normal. Serum protein electrophoresis showed no monoclonal gammopathy while urine protein electrophoresis showed strong albumin and transferrin bands. A kidney ultrasound was performed and was unremarkable. He had no other significant past medical history. The patient denied chronic use of non-steroidal anti-inflammatory drugs. He had no family history of renal disease. Based on the creatinine level of 1.1, lack of hematuria and sub-nephrotic range proteinuria the nephrologist did not recommend a renal biopsy. The patient was, however, started on an angiotensin-converting enzyme inhibitor regimen. The patient requested to continue using adalimumab with careful monitoring of his renal function. His proteinuria has been stable while continuing adalimumab. Recently, cases of nephrotic syndrome and glomerulonephritis have been reported in patients receiving TNF-α inhibitors for rheumatoid arthritis. A recent case report documented the development of an ANCA-positive vasculitis with glomerulonephritis in a patient taking adalimumab for rheumatoid arthritis. We are not aware of any previous reports of nephrotic syndrome or glomerulonephritis developing in patients taking adalimumab for psoriasis. It is possible that the development of proteinuria in this patient is not related to his use of adalimumab. A primary glomerulonephritis or amyloidosis is a diagnostic possibility that cannot be excluded without a renal biopsy. The mechanisms underlying the development of proteinuria and glomerulonephritis in patients receiving TNF-α inhibitors is at present not clear but the development of pathogenic autoantibodies has been implicated. We report the development of sub-nephrotic range proteinuria in a patient being treated with adalimumab for psoriasis. Case reports have demonstrated the development of glomerulonephritis in patients receiving anti-TNF-α antibodies for rheumatoid arthritis. It is important for dermatologists to be aware of this possible complication when treating psoriasis patients with anti TNF-α antibodies.