Merkel Cell Carcinosarcoma With a Bland Sarcomatous Component.

ABSTRACT: Merkel cell carcinoma with a sarcomatous component is very rare, with only 12 cases reported in the literature, often with overtly malignant myoid differentiation. We report a case of metastatic Merkel cell carcinosarcoma presenting in a lymph node 6 months after a diagnosis of cutaneous Merkel cell carcinoma with conventional histologic features. The metastatic lesion showed a unique biphasic appearance with admixed populations of neuroendocrine epithelial cells and fascicles of mitotically active spindle cells with mild cytological atypia. In addition to the immunomorphological features, a common molecular profile between the epithelial and mesenchymal components further supported the notion of carcinosarcoma in this case. To the best of our knowledge, a bland sarcomatous component has not been previously described in Merkel cell carcinosarcoma, which can be easily overlooked as a reactive stromal reaction microscopically.

Correlation of FISH and PRAME Immunohistochemistry in Ambiguous Superficial Cutaneous Melanocytic Proliferations.

ABSTRACT: Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated repressor of retinoic acid signaling which is expressed in melanoma and has emerged as a potential biomarker for malignant behavior in melanocytic neoplasms. Although ancillary molecular techniques such as fluorescence in situ hybridization (FISH) are established techniques in the diagnosis of problematic cutaneous melanocytic proliferations, they are expensive, time-consuming, and require appropriate infrastructure, which places them out of reach of some laboratories. The advent of readily available commercial antibodies to PRAME has the potential to provide a more accessible alternative. The aim of this study was to determine whether immunohistochemistry for PRAME could serve as a surrogate for FISH analysis in a subgroup of challenging superficial melanocytic proliferations. Cases which had previously been submitted for FISH analysis were stained for PRAME and interpreted by a panel of at least 3 dermatopathologists is a blinded fashion. Of a study set of 55 cases, 42 (76%) showed a pattern of PRAME immunostaining which was concordant with the cytogenetic interpretation, with an unweighted kappa of 0.42 (representing mild-to-moderate agreement). Thus, although there was a correlation between positive immunohistochemistry for PRAME and abnormal findings on FISH analysis, in our view, the concordance was not sufficient to enable PRAME immunohistochemistry to act as a surrogate for FISH testing. Our findings reiterate the principle that interpretation of problematic superficial melanocytic proliferations requires a synthesis of all the available data, including clinical scenario, morphological features, immunohistochemistry, and ancillary molecular investigations.

Histiocytoid Melanoma.

While most melanomas display well-characterised and readily recognised architectural and cytomorphological features, unusual variants can create diagnostic difficulties. Variants which mimic benign or reactive processes are particularly problematic. We report 5 cases of melanoma characterised by a subtle microscopic appearance reminiscent of a benign dermal histiocytic infiltrate, which we refer to as "histiocytoid melanoma." These lesions are characterised clinically by ill-defined areas of cutaneous pigmentation, which in several cases reached large proportions. Microscopically, there is a subtle interstitial pattern of infiltration by predominantly single cells with a histiocytoid morphology, often resembling melanophages. Immunohistochemical confirmation was typically required, with the cells showing positive labelling for Sox-10 as well as Melan-A. In several examples, the proliferation extended to clinically uninvolved surgical margins, necessitating multiple excisions, and many of our patients have experienced locoregional recurrence. However, none have developed distant metastases or died of melanoma. While uncommon, this subtle variant is important to recognise in order to ensure adequate histological clearance is obtained.

Two cases of adenosquamous carcinoma of the cervix with extensive in situ and invasive endometrial extension.

Adenosquamous carcinoma of the cervix is rare. It is defined as having both glandular and squamous cell differentiation, each component malignant and clearly seen on haematoxylin and eosin-stained slides alone. We report two cases of adenosquamous carcinoma of the uterine cervix, both of which showed in situ and invasive components and both of which showed cephalad extension to involve the endometrium with invasive squamous and adenocarcinomatous components. The mechanisms for cephalad endomyometrial extension is discussed, as are the potential implications for management and staging.

Large nested melanoma: a clinicopathological, morphometric and cytogenetic study of 12 cases.

A group of melanomas characterised by predominant growth as large nests within the epidermis has been described. These cases present a diagnostic challenge, as many traditional architectural criteria for the recognition of melanoma are absent. We report the clinical, histological, immunohistochemical, morphometric and cytogenetic features of a series of 12 cases of large nested melanoma. In this series, large nested melanoma accounted for 0.2% of cases of melanoma. The majority occurred on the trunk of middle aged patients with absent or minimal solar elastosis and 42% were associated with a component of benign intradermal melanocytic naevus, speaking to classification of these melanomas as falling within the spectrum of lesions developing in skin with low cumulative sun damage. In 67% of cases invasive melanoma was present. Criteria such as asymmetry, variation in nest size and intraepidermal nests with an underlying rim of junctional keratinocytes appear to be highly specific, and are strongly predictive of typical cytogenetic abnormalities of melanoma, which were identified in 92% of cases. Conversely, in addition to features which are definitionally absent or limited, features such as solar elastosis and cytological atypia do not appear to be particularly helpful in recognition of this variant.

Immunohistochemical staining for p16 is a useful adjunctive test in the diagnosis of Bowen's disease.

AIMS: The aim of this study was to document the pattern of immunohistochemical staining seen with p16 (INK4a) in actinic keratosis, Bowen's disease and seborrhoeic keratosis. METHODS: We gathered 20 examples each of actinic keratosis, Bowen's disease and seborrheic keratosis. The cases were stained for p16 using standard immunohistochemical techniques, and the staining patterns were categorised into one of five different patterns. RESULTS: All cases of Bowen's disease as defined in our practice showed strong positive staining in all abnormal cells, and 95% of these cases showed a distinctive pattern of sparing in a layer of palisaded basal cells. None of the actinic keratoses or seborrheic keratoses, as defined by our morphological criteria, showed this distinctive pattern. CONCLUSIONS: Bowen's disease, as we define the term, shows a distinctive, repeatable pattern of staining with p16, characterised by moderate to strong staining of all abnormal cells with sparing of a layer of basal cells. This pattern is not seen in actinic keratoses or in seborrheic keratoses. Thus immunohistochemistry for p16 is a useful adjunctive test in the differential diagnosis of these lesions.

Histopathological features associated with application of black salve to cutaneous lesions: a series of 16 cases and review of the literature.

AIMS: To document the histopathological features of self-treatment of cutaneous lesions with the escharotic agent black salve. METHODS: Retrospective review of cutaneous lesions treated with black salve retrieved from the files of four pathology practices in Western Australia and review of the published literature. RESULTS: 16 lesions from 11 patients who self administered black salve for the treatment of skin lesions were reviewed. Clinical diagnoses at the time of biopsy included scar, keloid scar, pseudomelanoma, basal cell carcinoma, squamous cell carcinoma and cutaneous necrosis. Histopathological features identified in our series included scarring, granulomatous inflammation, implanted foreign material, reactive stromal atypia and suppurative necrosis. Residual neoplasia was present in two of 16 cases, including a basal cell carcinoma and a melanocytic naevus. An additional 13 lesions in 10 patients were identified in the medical literature, including cases with poor cosmetic outcomes and cases of malignant tumours masked by uncontrolled escharotic treatment. CONCLUSIONS: Availability of black salve through easily accessible internet sites appears to be associated with persisting use of this agent for the self-management of cutaneous lesions. Awareness of the potential complications and range of histopathological features associated with self-administration of escharotic agents is of importance to dermatologists and histopathologists.

Interobserver variability in the diagnosis of circumscribed sebaceous neoplasms of the skin.

AIMS: Separation of sebaceous adenoma, sebaceoma and well differentiated sebaceous carcinoma is a clinically important distinction which relies on a number of subjective criteria. In routine practice we had noted significant interobserver variability in the classification of these lesions. This study sought to determine the degree of interobserver variability between general surgical pathologists and dermatopathologists in the diagnosis of well differentiated cutaneous sebaceous neoplasms. METHODS: We circulated 61 examples of well circumscribed cutaneous sebaceous neoplasms to nine pathologists, including dermatopathologists and general surgical pathologists who were asked to submit a diagnosis for each case. Fleiss' kappa statistic was used for assessment of interobserver agreement. RESULTS: We found that only seven cases (11%) had consensus agreement across all nine pathologists. Many cases had multiple diagnoses suggested, with three or more submitted diagnoses in 26 cases (43%), while 38 cases (62%) were diagnosed as sebaceous carcinoma by at least one pathologist. There was marked variability amongst the individual pathologists in the proportion of cases diagnosed as carcinoma, ranging from 5% to 57% of cases. Fleiss' kappa statistic for all pathologists across all diagnostic categories was 0.44, amounting to only fair to moderate agreement. CONCLUSIONS: These data indicate that there is substantial interobserver variability in the diagnosis of well circumscribed sebaceous neoplasms. This was seen in both the separation of benign and malignant lesions, as well as in the classification of the benign entities. This interobserver variability is likely to have significant clinical implications in terms of potential for over- or under-treatment, as well as in selection of cases for mismatch repair protein evaluation.

Axonal numbers in the greater auricular nerve: is there enough to go round?

HYPOTHESIS: Does the greater auricular nerve (GAN) have an appropriate number of myelinated axons for use as an interposition graft for the facial nerve? BACKGROUND: Previous studies have suggested that the GAN has a suitable cross-sectional and fascicular area for use as an interposition graft for the facial nerve. In this study, counts of myelinated axons in the GAN have been undertaken to assess, at a microscopic level, its suitability as such a graft. METHODS: Six GANs were examined, and the total myelinated axonal counts and axonal density per square millimeter of fascicular area were calculated. These counts were compared with previous studies on the facial nerve. RESULTS: Axonal density per square millimeter was comparable between greater auricular and facial nerves. However, there were significantly lower numbers of myelinated axons in the GAN compared with the published facial nerve data. CONCLUSION: The findings support the concept of "doubling over" the GAN to act as an appropriate interpositional facial nerve graft when there is a size mismatch between the two.