Kelli A. Hutchens

Mobile teledermatopathology: using a tablet PC as a novel and cost-efficient method to remotely diagnose dermatopathology cases.

Abstract:Dermatopathology has relatively few studies regarding teledermatopathology and none have addressed the use of new technologies, such as the tablet PC. We hypothesized that the combination of our existing dynamic nonrobotic system with a tablet PC could provide a novel and cost-efficient method to remotely diagnose dermatopathology cases. 93 cases diagnosed by conventional light microscopy at least 5 months earlier by the participating dermatopathologist were retrieved by an electronic pathology database search. A high-resolution video camera (Nikon DS-L2, version 4.4) mounted on a microscope was used to transmit digital video of a slide to an Apple iPAD2 (Apple Inc, Cupertino, CA) at the pathologist’s remote location via live streaming at an interval time of 500 ms and a resolution of 1280/960 pixels. Concordance to the original diagnosis and the seconds elapsed to reaching the diagnosis were recorded. 24.7% (23/93) of cases were melanocytic, 70.9% (66/93) were nonmelanocytic, and 4.4% (4/93) were inflammatory. About 92.5% (86/93) of cases were diagnosed on immediate viewing (<5 seconds), with the average time to diagnosis at 40.2 seconds (range: 10–218 seconds). Of the cases diagnosed immediately, 98.8% (85/86) of the telediagnoses were concordant with the original. Telepathology performed via a tablet PC may serve as a reliable and rapid technique for the diagnosis of routine cases with some diagnostic caveats in mind. Our study established a novel and cost-efficient solution for those institutions that may not have the capital to purchase either a dynamic robotic system or a virtual slide system.

Comparison between Langerhans cell concentration in lichen planopilaris and traction alopecia with possible immunologic implications.

Lichen planopilaris and long-standing traction alopecia are both traditionally classified as scarring alopecias. The etiology of lichen planopilaris has not been fully elucidated, although an autoimmune mechanism is generally accepted with Langerhans cell involvement implicated in previous studies. The etiology of traction alopecia is generally considered to be the result of mechanical force with subsequent inflammation without an autoimmune component. Langerhans cells in pure traction alopecia have not been previously evaluated nor have Langerhans cell concentrations been compared among the scarring alopecias. We performed double immunostaining with CD1a and CD3 to assess the ratio of Langerhans cells to T lymphocytes in lichen planopilaris and traction alopecia. Sixteen biopsies were evaluated including 9 biopsies of lichen planopilaris and 7 biopsies of traction alopecia. The mean ratio of the concentration of Langerhans cells to T lymphocytes was 1.28 for the lichen planopilaris group and 0.59 for the traction alopecia group. There is a significantly higher ratio of Langerhans cells to T lymphocytes in lichen planopilaris compared with that seen in traction alopecia. This supports previous data recognizing an immune component in lichen planopilaris mediated by Langerhans cells while emphasizing that most traction alopecias are not primarily immune related. Thus, the traditional classification systems for alopecia may need review and revision, especially when looking at etiopathogenesis. However, rare cases of traction alopecia demonstrated ratios similar to those seen in lichen planopilaris. These cases may represent the recently described “traction alopecia” condition, cicatricial marginal alopecia or changes seen in long-standing lesions, emphasizing the need for inclusion of distribution and duration within the clinical information.

The microenvironment in primary cutaneous melanoma with associated spontaneous tumor regression: evaluation for T-regulatory cells and the presence of an immunosuppressive microenvironment.

Spontaneous tumor regression, regression in the absence of therapeutic intervention, can be identified histologically in over 25% of primary cutaneous melanomas at initial diagnosis. A unique subset of T lymphocytes found in areas of regression can be histologically distinguished from tumor-infiltrating T lymphocytes (TIL) found in areas of tumor progression. We call this unique subset of T lymphocytes regression-associated T lymphocytes (RATs). The aim of this study is to determine the phenotype of lymphocytes and the density of specific cell types linked to immunosuppression in areas of tumor progression compared with areas of tumor regression. These specific cell types include T-regulatory cells (Tregs) and S100A9+ cells. A total of 14 primary cutaneous melanomas with areas of progression and regression were used. Immunohistochemistry staining was used to identify CD4+ cells, CD8+ cells, Tregs, and S100A9+ cells. Two independent observers manually counted three high-powered ×40 fields. There was no predominance of CD4+ or CD8+ T lymphocytes in either RATs or TIL. We identified a lower density of Tregs in RATs compared with TIL when using the FOXP3+/CD4+ Treg marker (P=0.04) and a marginal difference when using our second, confirmatory Treg marker, FOXP3+/CD25+ (P=0.11). We observed a lower density of S100A9+ cells in RATs compared with TIL (P=0.002). There was an observable difference in the tumor microenvironments of RATs and TIL, with RATs having a significantly lower density of Tregs and S100A9+ cells. We deduce that the absence of immunosuppression in areas of regression allows for a more robust immune response and thus effective eradication of tumor cells.

Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell-cell adhesion.

Fyn, a member of the Src family kinases (SFK), is an oncogene in murine epidermis and is associated with cell–cell adhesion turnover and induction of cell migration. Additionally, Fyn upregulation has been reported in multiple tumor types, including cutaneous squamous cell carcinoma (cSCC). Introduction of active H‐Ras(G12V) into the HaCaT human keratinocyte cell line resulted in upregulation of Fyn mRNA (200‐fold) and protein, while expression of other SFKs remained unaltered. Transduction of active Ras or Fyn was sufficient to induce an epithelial‐to‐mesenchymal transition in HaCaT cells. Inhibition of Fyn activity, using siRNA or the clinical SFK inhibitor Dasatinib, increased cell–cell adhesion and rapidly (5–60 min) increased levels of cortical F‐actin. Fyn inhibition with siRNA or Dasatinib also induced F‐actin in MDA‐MB‐231 breast cancer cells, which have elevated Fyn. F‐actin co‐localized with adherens junction proteins, and Dasatinib‐induced cell–cell adhesion could be blocked by Cytochalasin D, indicating that F‐actin polymerization was a key initiator of cell–cell adhesion through the adherens junction. Conversely, inhibiting cell–cell adhesion with low Ca2+ media did not block Dasatinib‐induced F‐actin polymerization. Inhibition of the Rho effector kinase ROCK blocked Dasatinib‐induced F‐actin and cell–cell adhesion, implicating relief of Rho GTPase inhibition as a mechanism of Dasatinib‐induced cell–cell adhesion. Finally, topical Dasatinib treatment significantly reduced total tumor burden in the SKH1 mouse model of UV‐induced skin carcinogenesis. Together these results identify the promotion of actin‐based cell–cell adhesion as a newly described mechanism of action for Dasatinib and suggest that Fyn inhibition may be an effective therapeutic approach in treating cSCC.

Unusual clinical presentation of cutaneous angiosarcoma masquerading as eczema: a case report and review of the literature.

An unusual case of cutaneous angiosarcoma clinically mimicking eczema is described. A 98-year-old Caucasian male presented with a 6-month history of a flesh-colored, subcutaneous nodule on his left forehead with contralateral facial erythema and scaling that had been previously diagnosed as eczema. Despite treatments with topical steroids and moisturizers, the condition did not resolve. At our clinic, excisional biopsy of the forehead lesion and scouting biopsies from the contralateral cheek were performed which revealed cutaneous angiosarcoma. The described case illustrates that dermatitis-like features should be considered as a rare clinical manifestation of cutaneous angiosarcoma. It also demonstrates that these lesions may respond well to radiotherapy as a single modality.

Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC.

Blastomycosis and Pregnancy: An Unusual Postpartum Disease Course.

Blastomyces dermatitidis is responsible for systemic mycoses. It is predominantly caused by inhalation of spores and often manifests as pneumonia, which can potentially disseminate; however, direct cutaneous inoculation may also occur. Blastomycosis in the perigravid period is exceedingly rare. The partial immunosuppressive state induced by pregnancy can engender more severe infections and is associated with a risk of vertical transmission. Published cases describe postpartum symptomatic improvement accompanying immune reconstitution, even in the absence of treatment. We present a 31-year-old gravid female with multifocal cutaneous blastomycosis. After delivering a healthy full-term infant with no evidence of congenital infection, the patients cutaneous lesions continued to worsen. At 6 weeks postpartum she was treated with oral itraconazole and demonstrated clinical improvement after 5 months of therapy. This case highlights the importance of prompt disease recognition, understanding of risk factors and initiation of appropriate antifungal therapy of blastomycotic infection occurring in the unique setting of pregnancy.

Changing Dermatopathology Protocols for Processing Small Skin Biopsies: Decreases in Slide Quantity Does Not Affect Patient Care and Allows for Optimal Efficiency.

Abstract:In dermatopathology, no standard protocol exists for processing small biopsy specimens. In our original protocol, 2 routine initial slides per biopsy were prepared. For 1003 biopsies, we noted how often the second slide helped in diagnosis or eliminated the need for additional deeper sections. After obtaining these data, we switched to processing only 1 initial slide (new protocol) and again evaluated 1003 biopsies. During the original protocol, the second slide never helped to make a diagnosis that was not apparent on the first slide. When deeper sections were ordered (10.4% of cases), they helped in the diagnosis 34.6% of the time. In the new protocol, deeper sections were ordered in 15.9% of cases and helped in the diagnosis 32.7% of the time when ordered. Comparing rates of deeper sections ordered showed no significant difference for benign, inflammatory/reactive, and premalignant/malignant groups (P > 0.1). However, there was a significant increase in deeper sections ordered for melanocytic lesions from 16.9% to 32.3% (P < 0.05). Also, a significantly greater percentage of punch biopsies (31.5% and 42.0% in the respective protocols) required deeper sections than shave biopsies (7.4% and 12.6% in the respective protocols). Switching protocols, the estimated annual cost savings is

A Rare Collision in Dermatopathology: Basal Cell Carcinoma and Atypical Fibroxanthoma.

2890. The majority of cases at our institution are properly diagnosed using only 1 slide. From our study findings, we conclude that 1 slide preparation for small biopsies is the best practice for our institution and one that does not affect diagnostic accuracy, reduces costs, and helps in effective time management.

Eosinophilic cytoplasmic inclusion bodies in vesicular multinucleated melanocytes: a clue to the diagnosis of benign melanocytic lesions.

To the Editor: We present the second report of a rare collision tumor comprised of a basal cell carcinoma (BCC) and an atypical fibroxanthoma (AFX) in a 64-year-old white man, who presented for evaluation of a bleeding growth on his right temple. The lesion had been present for several years but was becoming larger and increasingly pruritic over the past 3 months. On physical examination, a 3.5-cm pink, pearly irregularly shaped plaque was noted over the right temple, with light brown crust along the edges. A hyperpigmented focus was noted at the inferior aspect of the plaque with overlying erosions (Fig. ​(Fig.11). FIGURE 1 A 3.5-cm pink, pearly irregularly shaped plaque was noted over the right temple, with light brown crust along the edges and a hyperpigmented focus at the inferior aspect. Histologic examination revealed a mass with 2 different histologic patterns (Fig. ​(Fig.2).2). One part of the tumor exhibited features consistent with a classic BCC, comprised of islands and nests of basaloid cells, originating from the basal layer of the epidermis and extending into the dermis, with peripheral palisading and focal epidermal-stromal clefting, surrounded by a mucinous stroma (Fig. ​(Fig.3).3). Adjacent to and intermixed with the first tumor was an infiltrating spindle cell proliferation in a haphazard arrangement that abutted the epidermis but did not appear to be connected to it (Figs. ​(Figs.4,4, ​,5).5). The cells demonstrated marked pleomorphism with hyperchromasia, abundant eosinophilic cytoplasm, and prominent nucleoli. The tumor cells contained both typical and atypical mitoses with an index of 1–4 mitoses per high-power field. Multiple giant cells, scattered acute and chronic inflammation, ectatic capillary vessels, and focal hemorrhage were present. Perineural infiltration, lymphovascular invasion, and necrosis were not identified in the planes of section examined. Both tumors were transected laterally and at the base. The classic BCC tumor cells were diffusely and strongly positive for Ber-EP4 (Fig. ​(Fig.6),6), whereas the spindle cells were diffusely and strongly immunoreactive for CD10 (Fig. ​(Fig.7).7). Based on the histologic and immunohistochemical findings, the case was diagnosed as a collision tumor comprised of AFX and BCC. Because of the fact that the tumor was broadly transected at the base, the more aggressive undifferentiated pleomorphic sarcoma (uPS) could not be excluded. FIGURE 2 A shave biopsy of skin consisting of 2 histologically distinct tumors. There is a cystic basaloid proliferation on the right and a spindle cell proliferation on the left. The area above the dashed line represents what would be viewed on a more superficial ... FIGURE 3 There is a basaloid proliferation of cells with nodular and cystic morphology, surrounded by a mucinous stroma (×10 objective). FIGURE 4 Adjacent to and abutting this component is a pleomorphic and mitotically active spindle cell proliferation (×10 objective). FIGURE 5 There is an infiltrating spindle cell proliferation in a haphazard arrangement that abuts but is not connected to the overlying epidermis. Marked pleomorphism and multiple atypical mitoses are present (×10 objective). FIGURE 6 Strong and diffuse Ber-EP4 positivity in the basaloid tumor component (×2 objective). FIGURE 7 Strong and diffuse CD10 positivity in the spindle cell tumor component (×2 objective). Because of the location of the lesion, morphology, and ill-defined margins, the decision was made to proceed with a Mohs excision. The residual BCC component of the tumor extended into the subcutis and was completely excised with no complications. There was no residual AFX component identified in the Mohs sections. Given the patients complicated dermatologic history, he will require at least annual follow-up. A collision tumor is defined as 2 or more histologically distinct neoplasms coexisting in the same anatomical location with clearly defined boundaries, and can pose clinical and histologic diagnostic challenges. This is especially true when they involve a combination of 2 malignant tumors, each with its own prognosis, treatment, and ability to metastasize, which cause additional risk to the patient if misdiagnosed. Although the exact etiology of collision tumors is unknown, most authors believe that these combinations occur serendipitously, either because of the high biopsy rate of the 2 tumors or the high incidence of both tumors in sun-exposed skin. However, others suggest that epithelial or stromal changes in 1 tumor can induce the formation of the other,1,2 or that both are derived from similar cell lineages.3 AFX is a rare component of collision tumors, with combinations including primarily malignant entities, such as Merkel cell carcinoma,4 squamous cell carcinoma in situ,5 and invasive melanoma.6,7 Although it is generally classified as a low-grade sarcoma, its clinical behavior remains controversial, with outcomes ranging from spontaneous regression8 to recurrence and distant metastatic disease,9,10 especially after incomplete excision.11 Because of the high rate of local recurrence and ability for metastatic disease, wide local excision with 1-cm margins or Mohs micrographic surgery are recommended.12,13 Many believe that AFX is a more superficial and less aggressive variant of uPS, for which treatment requires margins up to 4 cm in some reports.14 BCCs are common components of cutaneous collision tumors, with the most common combinations, in contrast to AFX, being with benign entities, such as melanocytic nevus, seborrheic keratosis, and neurofibroma.15 Because of the indolent course and extremely low incidence of metastases (0.0028%–0.55%)16 in BCC, they are often effectively managed by electrodessication and curettage or local excision with 4-mm margins. We present this case because the combination of BCC and AFX is a rare finding in collision tumors, with only 1 other case reported in the literature without discussion of possible therapeutic differences. Although the AFX component in our case represented a large portion of the biopsy, it is important that dermatopathologists be aware of this potential combination. If a more superficial shave biopsy had been performed on this patient (demonstrated by area above dashed line in Fig. ​Fig.2),2), it could have potentially lead to misdiagnosis of a focus of invasive BCC. The higher incidence of local recurrence and possibility of distant metastases for AFX requires a wider surgical margin and more attentive clinical follow-up. Additionally, a focus of AFX may represent the superficial portion of the more aggressive uPS, which would significantly alter the patients treatment and prognosis. We report this collision tumor as an interesting twist on a “routine” case of BCC.