Amanda F. Marsch

Medicolegal Issues with Regard to Melanoma and Pigmented Lesions in Dermatopathology

Understanding malpractice risk and practicing risk management strategies results in better care and a less stressful environment of practice. Errors in diagnosis are most commonly related to melanoma and neoplasms of the skin. To offset the threat of malpractice litigation, malpractice data can be used to focus safety efforts on common diagnostic errors. Recognition of sources of error in the analysis of pigmented lesions by dermatopathologists, and the development of new immunohistochemical or genotypic techniques for the recognition and distinction of malignant disease from benign pigmented lesions, will also provide important improvements in care and diagnosis in the future.

The effectiveness of annotated (vs. non‐annotated) digital pathology slides as a teaching tool during dermatology and pathology residencies

With todays technology, paraffin‐embedded, hematoxylin & eosin‐stained pathology slides can be scanned to generate high quality virtual slides. Using proprietary software, digital images can also be annotated with arrows, circles and boxes to highlight certain diagnostic features. Previous studies assessing digital microscopy as a teaching tool did not involve the annotation of digital images. The objective of this study was to compare the effectiveness of annotated digital pathology slides versus non‐annotated digital pathology slides as a teaching tool during dermatology and pathology residencies.

Melanoma — Epidemiology, Genetics and Risk Factors

The U.S. National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Cancer Statistics Review estimates over 70,000 people will be diagnosed and 9,000 will die from melanoma in the United States in 2012. Though melanoma can affect persons of essen‐ tially any age, it is mainly a disease of adulthood, with median ages of diagnosis and death between 61 and 68 years, respectively (Weinstock, 2012). Nonetheless, melanoma incidence is increasing across age groups, over the past several decades in the United States (Fig. 1) (Ekwueme et al., 2011). In 1935, the average American individual had a 1 in 1,500 lifetime risk of developing melanoma. In 2002, the approximate risk of developing melanoma increased to 1 in 68 individuals (Rigel, 2002). Globally, Australia and New Zealand have the highest incidence rate of melanoma, an abundance of fair-skinned residents living in a UV-rich geography widely believed to be a major factor (Lens and Dawes, 2004). The current melanoma risk for Australian and New Zealander populations may be as high as 1 in 50 (Rigel, 2010). Considering melanoma is being diagnosed more often in young adults, could be prevented by UV-avoiding behaviors, and can be associated with extensive morbidity and mortality, it is truly an emerging public health concern. Part of the apparent increase in melanoma incidence may be due to better surveillance and earlier detection (Erdmann et al., 2012) however, even with heightened melanoma awareness and screening, there seems to have been a real increase in melanoma incidence over the past several decades.

Histopathologic Distinguishing Features Between Lupus and Lichenoid Keratosis on the Face.

Background:The occurrence of lichenoid keratosis (LK) on the face is not well characterized, and the histopathologic distinction between LK and lupus erythematosus (LE) occurring on the face is often indeterminate. The authors aimed to describe differences between LE and LK occurring on the face by hematoxylin and eosin alone. Methods:Cases of LK and LE were obtained using computer-driven queries. Clinical correlation was obtained for each lupus case. Other diagnoses were excluded for the LK cases. Hematoxylin and eosin–stained sections were reviewed. Results:Forty-five cases of LK and 30 cases of LE occurring on the face were identified. Shared features included follicular involvement, epidermal atrophy, pigment incontinence, paucity of eosinophils, and basket-weave orthokeratosis. Major differences between LK and LE, respectively, included perivascular inflammation (11%, 90%), high Civatte bodies (44%, 7%), solar elastosis (84%, 33%), a predominate pattern of cell-poor vacuolar interface dermatitis (7%, 73%), compact follicular plugging (11%, 50%), hemorrhage (22%, 70%), mucin (0%, 77%), hypergranulosis (44%, 17%), and edema (7%, 60%). A predominate pattern of band-like lichenoid interface was seen more commonly in LK as compared with LE (93% vs. 27%). Conclusions:The authors established the occurrence of LK on the face and identified features to help distinguish LK from LE. Follicular involvement, basket-weave orthokeratosis, pigment incontinence, paucity of eosinophils, and epidermal atrophy were not reliable distinguishing features. Perivascular inflammation, cell-poor vacuolar interface, compact follicular plugging, mucin, hemorrhage, and edema favored LE. High Civatte bodies, band-like lichenoid interface, and solar elastosis favored LK.

A Dermatopathologist's Guide to Troubleshooting Immunohistochemistry--Part 2: Troubleshooting Immunohistochemical Tests in the Laboratory.

Abstract:Unexpected staining patterns can arise from problems occurring in any of the steps required for IHC, some of which are discussed in part I of this CME series. Whether used to differentiate benign from malignant tumors, identify tumor subtypes, subtypes of hematopoietic malignancies, or identifying targets for therapy, the pathologist must be intimately familiar with the potential pitfalls that are inherent in the IHC methodology to troubleshoot problems in the laboratory, and more importantly, when interpreting immunohistochemical staining, to avoid pitfalls of false-positive or false-negative stains.

A Dermatopathologist's Guide to Troubleshooting Immunohistochemistry Part 1: Methods and Pitfalls.

Abstract:Immunohistochemistry (IHC) is a method by which specific target antigens can be detected in formalin-fixed paraffin-embedded tissue and involves the use of monoclonal or polyclonal antibodies; visualization of specific tissue antigens is achieved through an enzymatic reaction that transforms a colorless chromogen to a colored one. These enzymes may be attached to the antibody through a protein–ligand method (eg, biotin–avidin or biotin–streptavidin) or through a secondary antibody. Epitopes that are masked by protein linkage during formalin fixation are unmasked using a retrieval system that either uses heat (heat-induced epitope retrieval) or proteolytic enzymes (proteolytic-induced epitope retrieval). Part 1 of this review will focus and elaborate on the available methodologies for IHC testing, common problems inherent to each technique, and how they can be resolved. Part 2 will focus on common problems and artifacts encountered during IHC staining, likely causes, and methods for addressing each problem.

State restrictions on the interstate practice of dermatopathology are unconstitutional: the tissue is the issue

The regulation of the interstate practice of dermatopathology, teledermatopathology and teledermatology is the subject of discussion in many recent articles. Laws and regulations in many states complicate such interstate practice, requiring the dermatopathologist to be licensed in the state where the biopsy is taken if the dermatopathologist practices in and is licensed in a different state. To date, this discussion has been from the viewpoint of the dermatopathologist or dermatologist. But, when seen from the patients viewpoint, its apparent that most such state regulation may be void as an unconstitutional infringement of a patients fundamental right of unrestricted interstate travel under the Constitution of the United States of America.

Multiple scattered erythematous nodules and ulcerations: answer.

DISCUSSION Chronic lymphocytic leukemia (CLL) is the most common leukemia in the United States, accounting for approximately 30% of leukemias found in adults. Overall, the risk of secondary cancers in patients with CLL is more than double that of the general population, and secondary cutaneous malignancies are frequent complications in patients with CLL. In particular, the risk of skin cancer in these patients is 8-fold higher as compared with the healthy population. Moreover, a link between melanoma and CLL has recently been recognized, including an increased risk of death from melanoma in these patients. Melanoma patients have a 16-fold increased risk of developing a lymphoma; conversely, patients with CLL have up to a 7.5 increased incidence of developing malignant melanoma. The question one may ask is, which one usually comes first? In a recent study of 55 patients who were diagnosed with both melanoma and lymphoma, 47.3% of patients were concomitantly diagnosed with lymphoma on pathological assessment of lymph nodes for staging of their melanoma. However, 40% of patients developed lymphoma subsequent to the diagnosis of melanoma after a median time interval of 41 months. CLL was the most common subtype in these patients. Other similar studies confirm the trend that melanoma generally precedes the diagnosis of CLL instead of the reverse situation. Uniquely, in our patient, CLL and melanoma were diagnosed simultaneously from a cutaneous biopsy, which is the first reported case to date. The patient underwent lymph node dissection as part of the management for his melanoma. Several nodes were noted to have an atypical lymphocytic infiltrate, including one that also had nodal melanoma. A diagnosis of small cell lymphoma (SLL) was confirmed by flow cytometry on an axillary node, which was reported to have 93% of CD19 and CD20 positive B cells, with lambda clonality. CD5 and CD10 were negative in this B-cell population. No evidence of peripheral blood involvement was found. CLL and SLL are essentially the same disease; when the majority of the disease burden involves the blood and bone marrow, the term CLL is used, whereas SLL is reserved for those cases in which the disease burden is located mainly within the lymph nodes. The patient will be followed by oncology. The rising incidence of melanoma and CLL has been attributed to both the inherent immune dysfunction present in CLL and with UV exposure. It is well known that patients with CLL have an increased susceptibility to infections, increased incidence of autoimmune conditions, and increased susceptibility to other cancers, independent of receiving chemotherapy for treatment of their CLL. The immune dysfunction seen in CLL involves a variety of aberrations, including a decrease in peripheral blood CD4/CD8 T-cell ratio, abnormal T-cell cytokine secretion profiles, impaired antigenpresenting capabilities, and an increase in regulatory T cells associated with inhibition of antitumor immunity in solid cancers. Alterations of the p16 pathway, which inhibit the tumor suppressor gene CDNK4, are common in both lymphomas and melanoma. Additional findings common to both entities are mutations in the tumor suppressor gene p53 and Bcl-2. Interestingly, peritumoral infiltrates analyzed in nonHodgkin lymphoma patients with nonmelanoma skin cancers showed that approximately 75% of the time, the infiltrates were composed of B-cell leukemia cells. The dysfunctional B cells are unable to suppress tumor cell growth, and this has led some authors to believe that these patients have more aggressive tumors heralding a worse prognosis. Histopathologically, CLL typically expresses a B-cell phenotype and is CD5+; however, among B-cell CLL, up to 20% do not express CD5, as seen in this case. In a study comparing the clinical behavior of CD5+ and CD52 CLL, patients with CD52 CLL were found to have significantly less lymph node involvement, were more frequently stage A according to the Binet classification, and more commonly had isolated splenomegaly at diagnosis. Another study found that CD52 patients with CLL had an overall better prognosis compared with CD5+ patients with CLL, with a significantly longer overall median survival by almost 13 months. Cutaneous lesions occur in approximately 25% of patients with CLL, the most common presentation being leukemia cutis. At the time of diagnosis of CLL, the skin is the most commonly involved nonlymphoid organ. Leukemia From the *Department of Dermatology, University of Illinois at Chicago, Chicago, IL; and †Ackerman Academy, New York, NY. The authors declare no conflicts of interest. Reprints: Amanda F. Marsch, MD, University of Illinois at Chicago, 808 S. Wood St, Chicago, IL 60612 (e-mail: amandafmarsch@gmail.com).

Multiple scattered erythematous nodules and ulcerations: challenge.

CLINICAL PATHOLOGIC QUESTION An 83 year-old male with no relevant medical history presented with multiple scattered, asymptomatic erythematous nodules and ulcers to the back, flanks, chest, and extremities (Figs. 1–3). A punch biopsy was performed from a lesion on the back. MICROSCOPIC FINDINGS Histopathologic evaluation shows an ulcerated epidermis beneath, in which lies a dermal proliferation of spindle cells associated with a dense, atypical lymphocytic infiltrate (Fig. 4). The spindle cell population demonstrated conspicuous mitotic activity and infiltrated through the lymphoid infiltrate in a somewhat plexiform fashion (Figs. 5, 6). The lymphoid infiltrate was composed of mostly small lymphocytes, some of which seemed atypical (Fig. 6). There was an

Pathology of the Ear

The external ear is exposed to weathering and trauma; it also has sparse vascularity, making it prone to infection and disease. The external location of the cutaneous ear makes it easily visible for diagnosis and accessible for treatment. In this article, the authors focus on diseases of the ear that are most commonly encountered and may be subject to surgical and medical evaluation and/or treatment. Epidemiology, pathogenesis, clinical course, and treatment for each disease entity are discussed.