Jodi Speiser

Notch-1 and Notch-4 biomarker expression in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) demonstrates lack of expression of hormone receptors and human epidermal growth factor receptor. However, there is no targeted therapy for TNBC. The authors analyzed 29 TNBC cases for Notch-1 and Notch-4 biomarker expression and subcellular location, Ki67 proliferation rate, and relevant clinical/survival data. Results demonstrated an unfavorable Ki67 rate in 90% of cases, Notch-1 expression in tumor and endothelial cells in 100% of cases, and Notch-4 expression in tumor cells in 73% of cases and endothelial cells in 100% of cases. Additionally, subcellular localization of Notch-1 and Notch-4 was predominantly nuclear and cytoplasmic. In conclusion, (a) the majority of TNBCs are high-grade infiltrating ductal carcinomas with high Ki67 proliferation rate and (b) both Notch-1 and Notch-4 receptors are overexpressed in tumor and vascular endothelial cells with subcellular localization different from that of hormone-positive breast cancer. Targeting Notch signaling with gamma secretase inhibitors should to be explored to further improve the survival rate of TNBC patients.

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.

Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo

Abstract:  To study protection of melanocytes from stress‐induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4‐TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4‐TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV‐treated explant cultures, in skin of successfully PUVA‐treated patients and in melanocytes cultured from vitiligo non‐lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO‐1 but not HO‐2 overexpression offers protection from stress‐induced cell death in MTT assays. HO‐1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients.

Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo.

Abstract:  To study protection of melanocytes from stress‐induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4‐TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4‐TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV‐treated explant cultures, in skin of successfully PUVA‐treated patients and in melanocytes cultured from vitiligo non‐lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO‐1 but not HO‐2 overexpression offers protection from stress‐induced cell death in MTT assays. HO‐1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients.

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.

Pernio as the presenting sign of blast crisis in acute lymphoblastic leukemia

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.

Mucinous hidradenoma in a child—A case report and review of the literature

A previously healthy 5‐year‐old girl presented with acute onset of blue toes and red spots on the nose and fingers. The striking nature of these lesions, along with the finding of submandibular lymphadenopathy, prompted further evaluation. Laboratory findings were remarkable for anemia, high transaminase levels, and high blast count. Histopathologic findings were consistent with early pernio. Further examination revealed acute B‐cell lymphoblastic leukemia. Treatment of the leukemia led to resolution of the pernio.

Comparison of three embedding media for preparation of frozen sections for Mohs micrographic surgery

Hidradenomas are benign tumors of the sweat glands that are rarely reported in childhood. The presence of mucinous change in hidradenomas, which consists of variable numbers of mucin‐rich goblet cells, is occasionally observed in some adult clinical practices. However, it has not been previously reported in the pediatric population. Herein, we present a unique case of a mucinous hidradenoma presenting on the thigh of a 3‐year‐old boy. The clinical presentation and histological features of the case, along with a literature review of published case reports of pediatric hidradenomas are described. We present this case in order to highlight this variant of hidradenoma and to reinforce its inclusion in the differential diagnosis of neoplasms/conditions of childhood with mucinous differentiation.

Development of Asymmetric Facial Depigmentation in a Patient Treated with Dasatinib with New-Onset Hypovitaminosis D: Case Report and Review of the Literature

with a maximum diameter of 0.9 mm, is the smallest melanoma that has ever been reported, and it presented as a changing lesion on an adult with dermatoscopic subtle gray color, these features being sufficient according to the Chaos and Clues algorithm to warrant excisional biopsy. The melanoma presented here, being 0.9 mm in diameter, is the smallest reported at this time. Every melanoma has to start small, and a threshold of 6 mm will prevent diagnosis at the earliest stages. We believe that especially in high risk patients, even very small lesions which have dermatoscopic clues to melanoma should be excised and submitted for pathological assessment.