[The value of histology in the diagnosis of non-neoplastic skin diseases]. / Nutzen der Histologie bei der Diagnostik nicht-neoplastischer Hauterkrankungen.

The value of histology in the diagnosis of non-neoplastic skin diseases Abstract. The diagnosis of most non-neoplastic skin diseases is primarily based on patient history and clinical examination. However, histological evaluation of skin biopsies can be an invaluable tool in the diagnostic workup of clinically uncertain inflammatory skin conditions. For a correct interpretation of the histological findings, clinicopathological correlation as well as selection of an adequate biopsy technique and a suitable biopsy site are essential. In this article, general principles related to biopsies of inflammatory skin diseases are discussed and illustrated with examples from everyday practice.

Androgen receptor status is highly conserved during tumor progression of breast cancer.

BACKGROUND: With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. METHODS: AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. RESULTS: AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). CONCLUSIONS: Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

High tumor budding stratifies breast cancer with metastatic properties.

Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass. In colon cancer high tumor budding is associated with positive lymph nodes and worse prognosis. Therefore, we investigated the value of tumor budding as a predictive feature of lymph node status in breast cancer (BC). Whole tissue sections from 148 surgical resection specimens (SRS) and 99 matched preoperative core biopsies (CB) with invasive BC of no special type were analyzed on one slide stained with pan-cytokeratin. In SRS, the total number of intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF) were counted. A bud was defined as a single tumor cell or a cluster of up to five tumor cells. High tumor budding equated to scores averaging >4 tumor buds across 10HPFs. In CB high tumor budding was defined as ≥10 buds/HPF. The results were correlated with pathological parameters. In SRS high PTB stratified BC with lymph node metastases (p ≤ 0.03) and lymphatic invasion (p ≤ 0.015). In CB high tumor budding was significantly (p = 0.0063) associated with venous invasion. Pathologists are able, based on morphology, to categorize BC into a high and low risk groups based in part on lymph node status. This risk assessment can be easily performed during routine diagnostics and it is time and cost effective. These results suggest that high PTB is associated with loco-regional metastasis, highlighting the possibility that this tumor feature may help in therapeutic decision-making.

Perineural Invasion in the Absence of Malignancy: Report of Two Cases and Review of the Literature.

Perineural invasion is usually associated with invasion of the perineural space by malignant tumors. In this report, we describe 2 cases of perineural infiltration by benign-appearing epithelial cells in the skin. One case concerns a tumor-free reexcision specimen of a basal cell carcinoma and the other one an ulceration at the outer ear, consistent with acanthoma fissuratum, without a history of a previous excision. This finding was interpreted as a reactive process with dislocation of epithelium from the overlying epidermis into the perineural space.

Clonality in sarcoidosis, granuloma annulare, and granulomatous mycosis fungoides.

The histological discrimination of granulomatous cutaneous T-cell lymphomas (CTCLs) from reactive granulomatous disorders such as sarcoidosis and granuloma annulare (GA) may be difficult due to overlapping histological features. We analyzed the T-cell receptor gene rearrangement in sarcoidosis and GA to investigate the value of the detection of clonal T cells as an adjunctive diagnostic marker in the differentiation between sarcoidosis and GA versus granulomatous CTCLs. Rearrangement of T-cell receptor γ genes was examined by the use of automated high-resolution polymerase chain reaction fragment analysis in 35 cases of sarcoidosis and 15 cases of GA and compared with a series of 19 cases of granulomatous CTCLs. A monoclonal T-cell population was found in none of the cases of sarcoidosis and in 2 of 15 cases of GA (13%). In granulomatous CTCLs, a neoplastic T-cell clone was detected in 94%. Presence of clonal T cells argues in favour of a granulomatous CTCL, while a polyclonal T-cell population makes the presence of a sarcoidosis or a GA more likely. The analysis of T-cell clonality is a useful diagnostic adjunct in the differentiation between sarcoidosis and GA from granulomatous CTCLs.

EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.

Primary cutaneous CD30(+) lymphoproliferative disorders (CD30(+) LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30(+) LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30(+) LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30(+) LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30(+) LPDs.

Merkel cell polyomavirus is present in common warts and carcinoma in situ of the skin.

Polyomaviruses have been linked to diseases of immunosuppressed patients. We sought to determine the prevalence of Merkel cell polyomavirus in benign epithelial skin neoplasms and nonmelanoma skin cancer of immunosuppressed renal transplant recipients and long-term dialysis patients. Merkel cell polyomavirus DNA was detected by polymerase chain reaction (PCR) in 2 (10%) of 20 patients, in carcinomas in situ (Bowen's disease). In one of our patients with Merkel cell polyomavirus-positive carcinoma in situ, 9 (39.1%) of 23 skin lesions at various anatomical locations tested positive for Merkel cell polyomavirus sequences by PCR, including all of his common warts (4/4), half of his carcinoma in situ lesions (3/6), and 2 of his 3 seborrheic keratoses. In a second cohort of immunosuppressed renal transplant recipients, Merkel cell polyomavirus DNA was found in 1 (6.3%) of 16 common warts and in 2 (9.5%) of 21 carcinomas in situ. In immunocompetent individuals, Merkel cell polyomavirus DNA was found in 2 (6.7%) of 30 common warts and in 2 (8.3%) of 24 carcinomas in situ. DNA of other human polyomaviruses was not detected in any of the investigated skin neoplasms. We conclude that common warts and carcinomas in situ can be positive for Merkel cell polyomavirus in immunosuppressed as well as immunocompetent individuals. Remarkably, some of the Merkel cell polyomavirus-positive common warts did not contain human papillomavirus. Furthermore, Merkel cell polyomavirus can be found in various skin neoplasms of the same individual.