Noreen Walsh

The Diagnostic Accuracy of in vivo Confocal Scanning Laser Microscopy Compared to Dermoscopy of Benign and Malignant Melanocytic Lesions: A Prospective Study

Background: The diagnosis of melanoma at an early, curable stage is an important challenge for clinicians. Confocal scanning laser microscopy (CSLM) is a high-resolution, noninvasive technology that may facilitate improved diagnostic accuracy over clinical examination. The aim of this study was to evaluate the diagnostic accuracy of CSLM compared to dermoscopy in a prospective examination of benign and malignant melanocytic lesions. Methods: 125 patients with suspicious pigmented lesions were prospectively recruited to undergo a clinical, dermoscopic and CSLM examination. A diagnosis was made preoperatively with each technique, and the lesion was then excised and diagnosed using histopathology. Results: 125 patients with 125 lesions were studied comprising 88 melanocytic nevi and 37 melanomas. Dermoscopy had a sensitivity of 89.2%, a specificity of 84.1%, a positive predictive value of 70.2% and a negative predictive value of 94.9%. CSLM was found to have a sensitivity of 97.3%, a specificity of 83.0%, a positive predictive value of 70.6% and a negative predictive value of 98.6%. No melanomas were misidentified when both techniques were used together. Conclusions: CSLM had a relatively higher sensitivity than dermoscopy; however, the specificity was similar with CSLM and dermoscopy. These results suggest that dermoscopy and CSLM are complementary.

Cutaneous sarcoidosis and foreign bodies

A histopathological diagnosis of sarcoidosis is, by convention, one of exclusion and is reached only when other potential causes of granulomatous disease, such as foreign bodies, are eliminated. We report herein three cases of systemic sarcoidosis with cutaneous manifestations of the disease, in which polarizable foreign particles were associated with the granulomata in the skin. We submit (a) that a granulomatous foreign body reaction and sarcoidosis are not mutually exclusive, (b) that paniculate foreign matter may actually serve as a nidus for granuloma formation in sarcoidosis, and (c) that the occasional presence of extraneous material within the granulomata of sarcoidosis requires greater recognition by pathologists.

Partial regression of primary cutaneous melanoma: is there an association with sub-clinical sentinel lymph node metastasis?

Whether partial regression of a primary melanoma has an adverse impact on prognosis is controversial. As an indirect mechanism of addressing this question we drew a correlation between the histopathological characteristics of 107 cutaneous melanomas and the presence of sub-clinical metastasis in corresponding sentinel lymph nodes. Partial regression of the primary tumor, defined as focal replacement of the lesion by a scar, unrelated to a previous biopsy, was observed in 20 (19%) cases in the group as a whole. Excluding cases in which an accurate Breslow thickness of the primary melanoma could not be established and/or the presence of a capsular nevus was detected in the sentinel node, a total of 97 remained. Seventeen cases (Breslow thickness 0.63–9.7; mean 2.4 mm) showed partial regression and 80 (Breslow thickness 0.25–7.00; mean 1.8 mm) were devoid of regression. Of the 17 cases with regression 5 (29%) had nodal metastasis (by histopathology and/or molecular analysis) and of the 80 cases without regression 23 (29%) had nodal metastasis (by one or both evaluations). Our data reveals no association between partial regression of the primary melanoma and sentinel node involvement by the disease. The Breslow thickness proved to be the only significant independent variable related to nodal metastasis. Of interest, ulceration of the primary lesion was significantly associated with nodal disease on univariate, but not on multivariate, analysis. While acknowledging that the cohort size may lack the statistical power to demonstrate subtle associations, our data supports the known relevance of tumor thickness and ulceration to regional lymph node metastasis and thereby, to outcome of melanoma in its early stages, but fails to support a similar role for partial regression.

Nevus cells in lymph nodes: An association with congenital cutaneous nevi

It is known that collections of nevus cells can occur in the collagenous framework of lymph nodes excised for a variety of reasons. These can be difficult to distinguish from nodal deposits of metastatic cancer but attention to cytologic detail, the distribution of the cells, and their immunohistochemical profile usually lead to a satisfactory conclusion. From another perspective, the mechanism by which nevus cells are deposited in lymph nodes has been a source of interest and controversy. Theories in this regard include embolic transfer of cells from cutaneous nevi to corresponding regional nodes and an aberration in the embryologic migration of melanocytes in utero. There have been tentative indications in the literature of a potential link between the presence of nevus cells in lymph nodes and cutaneous nevi in corresponding catchment areas of skin. In the course of evaluating sentinel lymph nodes from patients with melanoma, we noted a significant association between the presence of nodal nevi and cutaneous nevi in corresponding regional zones of skin (Fischers exact test, p = 0.021). The link with cutaneous nevi of congenital type was even stronger (Fischers exact test, p = 0.008). This consolidates previous sporadic reports of such an association and through further scrutiny may help shed light on the mechanism by which nodal and congenital cutaneous nevi are linked.

The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites ☆ ☆☆

Most Merkel cell carcinomas display pure neuroendocrine differentiation (pure Merkel cell carcinoma), whereas a minority show combined neuroendocrine and nonneuroendocrine elements (combined Merkel cell carcinoma). Recent identification of Merkel cell polyomavirus DNA and Merkel cell polyomavirus large T antigen expression in a proportion of Merkel cell carcinomas has suggested viral-induced oncogenesis. To date, Merkel cell polyomavirus immunohistochemistry has shown an absence of viral large T antigen expression in combined Merkel cell carcinoma as well as select non-Merkel cell carcinoma cutaneous lesions and visceral neuroendocrine tumors. In our series, we aimed to further characterize the frequency and pattern of Merkel cell polyomavirus large T antigen expression by CM2B4 immunohistochemistry in primary and metastatic Merkel cell carcinoma (pure Merkel cell carcinoma and combined Merkel cell carcinoma) and various non-Merkel cell carcinoma lesions from patients with Merkel cell carcinoma, patients without Merkel cell carcinoma, and individuals with altered immune function. Merkel cell polyomavirus large T antigen was detected in 17 (63%) of 27 pure Merkel cell carcinomas and absent in all 15 (0%) combined Merkel cell carcinomas. Furthermore, complete concordance (100%) of Merkel cell polyomavirus large T antigen expression was observed in 10 cases of primary Merkel cell carcinoma and subsequent tumor metastases. We also evaluated 70 non-Merkel cell carcinoma lesions including 15 cases each of pulmonary and gastrointestinal neuroendocrine tumors. All 70 non-Merkel cell carcinoma lesions were negative for Merkel cell polyomavirus by CM2B4 immunohistochemistry, irrespective of any known Merkel cell carcinoma diagnosis and immune status. In summary, our identification of Merkel cell polyomavirus large T antigen expression in a subset of Merkel cell carcinoma and lack of findings in combined Merkel cell carcinomas and non-Merkel cell carcinoma lesions concur with earlier findings and implicate Merkel cell polyomavirus-independent pathogenesis in these cases. Overall, CM2B4 immunohistochemistry appears to be a specific method for Merkel cell polyomavirus detection and has the potential to play an important role in the diagnosis and classification of Merkel cell carcinoma in the future.

Histopathology in erythroderma: review of a series of cases by multiple observers

This study examines the utility of objective histopathological studies in the evaluation of adult patients with erythroderma. A series of 56 skin biopsies, from 40 erythrodermic patients, was reviewed sequentially by 4 Canadian dermatopathologists who were unaware of clinical details of the cases. The final diagnosis (gold standard), in each instance, had already been determined by others, based on clinicopathologic data and response to therapy. Direct comparison revealed that the mean accuracy of I he histopathological diagnoses was 53% (range: 48‐(i6%). a favorable result in view of the difficulty of the task at hand. Additional points of information which evolved from the study are as follows: (i) identification, by microscopy alone, of spongiolic dermatitis, cutaneous T‐cell lymphoma and psoriasis, as underlying causes of eryihroderma was more successful than that of drug eruptions and pilyriasis rulira pilaris; (ii) the1 epidermotropism which characterizes cutaneous T‐cell lymphoma may be mistaken for inflammatory interface changes seen in drug eruptions and vice versa, thus constituting a pitfall in diagnosis; (iii) finally, it appears dial submission of multiple simultaneous biopsies, rather than a single specimen, from patients with erythroderma would be likely to enhance the accuracy of histopathological diagnosis.

A new look at nevus-associated melanomas

The frequency with which malignant melanomas arise in association with preexisting melanocytic nevi has been studied extensively. We opted to evaluate new aspects of this association. In particular, we addressed the relative proportions of acquired versus congenital nevi involved and categorized the acquired nevi according to morphological type. Approximately 23% of the melanomas (29 of 124) in this group arose in association with preexisting nevi of which 55% (n = 16) were acquired and 28% (n = 8) were congenital (small). In 17% (n = 5) a distinction could not confidently be made. Of the acquired nevi, the vast majority were of Clarks type. It is clear that a relatively small proportion of melanomas as a whole are associated with preexisting nevi, and this number should be kept in perspective in devising strategies for early detection and prevention. The involvement of Clarks nevi in this regard is known, but to date the role of small congenital nevi has been underrecognized.

Data set for pathology reporting of cutaneous invasive melanoma: Recommendations from the international collaboration on cancer reporting (ICCR)

An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may facilitate the development of protocols for other tumor types. Widespread utilization of an internationally agreed upon, structured pathology data set for melanoma will lead not only to improved patient management but is a prerequisite for research and for international benchmarking in health care.

The specificity of histopathology in erythroderma

Conflicting views about the diagnostic value of skin biopsy in the investigation of erythrodermic patients are extant. The objective of the present study was to establish the frequency with which a correct diagnosis can be based on histopathological assessment alone. This was achieved by comparison of the “blinded” microscopic diagnosis with the final diagnosis (based on combined clinico‐pathologic parameters and response to therapy). In a retrospective review of 56 skin biopsies from 40 patients with erythroderma, we found a positive correlation between the pathological diagnosis and the final diagnosis in 66%; furthermore, when the microscopic characteristics observed in different diagnostic categories were assessed, these proved lo simulate those seen in conventional manifestations of the various underlying diseases but tended to be subtle in the setting of erythroderma. We conclude that, despite the homogeneity of the clinical expression of erythroderma, diagnostic histopathological features of the underlying disease are retained in the majority of cases.

Exclusive involvement of folliculosebaceous units by herpes : A reflection of early herpes zoster

The histopathological changes of herpes simplex, herpes zoster, and varicella are considered to be indistinguishable from one another. Evaluation of the clinical setting, with adjunctive studies if necessary, generally clarifies the specific diagnosis. Vesicular lesions in all three conditions can involve epidermal and adnexal epithelium with characteristic cytopathic features. We describe three patients with non-vesicular eruptions on the head and neck whose biopsies revealed exclusive folliculosebaceous involvement by herpes. All three patients developed typical herpes zoster within days of the biopsy. There is compelling scientific evidence in the literature indicating that, in herpes zoster, the virus is transported from dorsal root or trigeminal ganglia via myelinated nerves to the skin. These terminate at the isthmus of hair follicles and primary infection of follicular and sebaceous epithelium occurs. Spread of infection to the epidermis follows. In contrast, data pertaining to recurrent herpes simplex indicates that axonal transport of the virus from sensory ganglia to the skin is directed primarily to the epidermis, via terminal non-myelinated nerve twigs. The clinical evolution of our three cases and scientific data in the literature indicate that exclusive folliculosebaceous involvement by herpes, in the setting of a non-vesicular eruption, represents early herpes zoster.