Diagnostic concordance among pathologists interpreting breast core biopsies on secondary review over a 1-year period at an Australian tertiary hospital.

This study provides data on the diagnostic concordance between initial and review diagnoses of all breast core biopsy cases at a single tertiary hospital in Western Australia over a 1-year period. A retrospective review of all breast core biopsy cases between January 1 and December 31, 2016, was carried out at PathWest, Fiona Stanley Hospital in Perth, Western Australia. Each biopsy is reported by a single pathologist and then reviewed within 1 week by a panel of intradepartmental subspecialist breast pathologists, who either agree with the original diagnosis, have a minor discordant diagnosis, or a major discordant diagnosis. Records for 2036 core biopsies were available between January 1 and December 31, 2016. Of these, 56.0% (n = 1141) were classified as benign, 34.3% (n = 699) as malignant, 7.2% (n = 147) as indeterminate, 2.3% (n = 46) as nondiagnostic, and 0.1% (n = 3) as suspicious for malignancy. In 99.1% (n = 2018) of cases, there was agreement between initial and review diagnoses. In total, 0.9% (n = 18) were disagreements: 0.49% (n = 10) were major discordant disagreements and 0.39% (n = 8) were minor discordant disagreements. All cases of major discordant disagreements would have resulted in significant changes to clinical management. This study demonstrates that an Australian institution is providing a high-quality pathology service with a low error rate between initial and review diagnoses of breast core biopsies. It reinforces the importance of secondary review of biopsies in a timely fashion for detecting potentially serious misdiagnoses that could lead to inappropriate management.

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.

Syndemic synergy of HPV and other sexually transmitted pathogens in the development of high-grade anal squamous intraepithelial lesions.

BACKGROUND: Anal intraepithelial neoplasia is associated with high-risk human papillomavirus (hrHPV) as a precursor to anal cancer. However, factors other than hrHPV are likely to be involved and further study of cofactors is required because of the possibility of syndemic interactions. METHODS: Three hundred and fourteen patients underwent 457 operations. Histopathology and hrHPV testing using the Digene Hybrid Capture 2 (HC 2) method were performed. Demographic factors and sexually transmissible infections (STIs) were recorded. RESULTS: Results showed that hrHPV alone was associated with HSIL (OR = 4.65, p < 0.001). None of the other STIs were alone associated with HSIL but amplification of risk was found when hrHPV infection occurred with HIV (OR = 11.1); syphilis (OR = 5.58); HSV 2 (OR = 7.85); gonorrhoea (OR = 6.45) and some other infections. CONCLUSIONS: These results suggest that hrHPV is a sufficient cause of anal HSIL. Seropositivity for HIV, HSV 2, T. pallidum, HBV and HCV and a history of gonorrhoea or chlamydia exert a powerful amplifying factor increasing the risk of HSIL above the risk with hrHPV alone. Other co-factors which are associated with an increased risk of HSIL are increased age, male gender, MSM behaviour and self-reported history of more than 50 sexual partners. This pattern of disease in patients with warts is characteristic of a syndemic with potential serious increased risk of anal carcinoma.

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.

Peri-implant galactocele following vacuum-assisted core biopsy of the breast: a cautionary tale.

A lactating woman in her early 40s with a strong family history of breast cancer presented with a markedly swollen breast days after having a vacuum-assisted core biopsy performed to sample indeterminate microcalcifications in her left breast. Ultrasound showed a large peri-implant fluid collection which yielded milky fluid on aspiration consistent with galactocele formation. Histology of the core specimens revealed a fragment of fibrous capsule suggesting that the core biopsy had created a fistula between the breast tissue and the peri-implant space. Bromocriptine was given and the galactocele slowly resolved.

Multiple minute digitate hyperkeratosis: a proposed algorithm for the digitate keratoses.

BACKGROUND: Multiple minute digitate hyperkeratosis (MMDH) is a rare disorder of keratinization with many different names. OBJECTIVE: We present a case of MMDH and review the literature. We propose and discuss the classification the digitate keratoses, which include MMDH, lichen spinulosus, phrynoderma, spiny keratoderma, arsenical keratosis, multiple filiform verrucae, postirradiation digitate keratosis, trichodysplasia spinulosa, and hyperkeratotic spicules. We present a table of suggested and synonymous terms and propose a diagnostic algorithm for these digitate keratoses. METHODS: A literature search using PubMed and MEDLINE was performed. This included the search terms "MMDH," "familial disseminated filiform hyperkeratosis," "punctate porokeratotic keratoderma," "disseminated spiked keratosis," "minute aggregate keratosis," "digitate keratosis," "conical keratosis," "hyperkeratotic spicules," and "music box spine dermatosis." A case of MMDH in an 89-year-old woman is described. RESULTS: The digitate keratoses are presented alongside their synonymous terms and are divided into those that are generalized or localized using an algorithm. LIMITATIONS: Separate disease entities are likely to arise within the digitate keratoses with increased reporting of immunohistochemical keratin analysis and molecular genetic studies. CONCLUSION: We report a new case of MMDH and provide a clinical approach to diagnosis of the digitate keratoses.

Oncocytic adrenocortical neoplasms--a clinicopathologic study of 13 new cases emphasizing the importance of their recognition.

Oncocytic adrenocortical neoplasms (OANs) are a rare but important subtype of adrenal tumors with unique clinical and morphological features. We present 13 previously unpublished cases, of which 3 were classified as benign, 2 as having borderline malignant potential, and 8 as malignant according to the Lin-Weiss-Bisceglia criteria. Seven tumors (54%) showed evidence of endocrine activity. All were composed of more than 90% oncocytes confirmed immunohistochemically using the antimitochondrial antibody mES-13 and ultrastructurally in 4 cases. Small oncocytes were a frequent finding that challenges the conventional notion of oncocytes as necessarily having abundant cytoplasm. Most cases were immunoreactive for vimentin, synaptophysin, inhibin-α, melan A, and calretinin, the latter being a novel finding in this group of neoplasms. Cytokeratin positivity with AE1/AE3 and CAM5.2 was variable. The literature was comprehensively reviewed to identify all cases of OANs reported to date. Hormone production is not as uncommon as previously believed, occurring in 30%. The Lin-Weiss-Bisceglia criteria were retrospectively applied to all published cases with sufficient information and were shown to effectively separate tumors according to their future risk of recurrence and survival using Kaplan-Meier survival curves (log-rank test, P < .001 for both). The estimated overall median survival for malignant oncocytic neoplasms is 58 months (95% confidence interval = 27.5-88.5 months), providing the first preliminary evidence that the prognosis of malignant OANs is likely to be more favorable than conventional adrenocortical carcinomas, in which the reported median survival is between 14 and 32 months.

The clinical significance of cytokeratin-positive cells in lymph nodes at the time of mastectomy from patients with ductal carcinoma-in-situ.

BACKGROUND: We determined the presence or absence of and clinical significance of cytokeratin-positive cells in the lymph nodes of patients who had had mastectomies for ductal carcinoma-in-situ. METHODS: Two pathologists independently assessed the axillary lymph nodes found. All patients had either a core or open biopsy performed before the time of mastectomy. The lymph nodes were assessed with hematoxylin and eosin stain and immunohistochemistry for cytokeratin marker AE1/AE3. The slides were assessed for the presence or absence of epithelial cells. As a control, axillary lymph nodes found in prophylactic mastectomies were assessed. None of these had had a previous biopsy performed. RESULTS: Lymph nodes from all patients demonstrated no obvious epithelial cells on hematoxylin and eosin stain. Peripheral sinuses of lymph nodes from six patients (23%) who had mastectomies for ductal carcinoma-in-situ contained a few cytokeratin-positive cells on immunohistochemistry. The lymph nodes of the control group demonstrated no cytokeratin-positive cells. The mean follow-up of patients was 5 years, and all patients were alive without recurrence at the time of the study. CONCLUSIONS: Epithelial cells may be present in the lymph nodes draining a site of recent breast biopsy in the absence of invasive carcinoma, indicating that these are an artifact of recent surgery and not of micrometastatic disease.