Hedgehog pathway mutations are involved in the pathogenesis of plaque-type "trichoblastoma": A report of two cases.

We present two cases of plaque-type trichoblastoma with atypical foci. A rare variant of trichoblastoma is the plaque variant, which is characterized by poor circumscription and locally infiltrative growth pattern. These lesions mostly require multiple stages of Mohs micrographic surgery. Debate still exists whether this variant should be considered as a benign entity or as "low-grade" malignant counterpart of trichoblastoma. In this report we describe two cases of plaque-type trichoblastoma with atypical foci, which harbored somatic mutations in the Hedgehog pathway, thus should be acknowledged as intermediate malignancies. In addition, extensive molecular workup of both the trichoblastic and atypical component in sequential lesions in the same patient was performed.

Histopathology of Red Tattoo Reactions.

BACKGROUND: Despite popularity of tattoos, complications may occur. In particular, red tattoo reactions due to allergic reactions are the most frequent chronic tattoo reactions. However, little is known about its histopathology and underlying pathomechanisms. OBJECTIVE: The aim of this article is to analyze the histopathology of red tattoo reactions for diagnostic purposes and to acquire more insight into pathogenesis. METHODS: A retrospective cross-sectional study was conducted by reviewing the histopathology of 74 skin biopsies of patients with allergic red tattoo reactions. Histopathological findings, such as inflammation patterns, inflammatory cells and pigment depth and color, were semi-quantified with an in-house validated scoring system by 2 independent senior investigators. RESULTS: Histiocytes and lymphocytes were both present in >93%. Histiocytes were the predominant inflammatory cells in 74.3%, but well-defined granulomas were mostly absent (78.0%). Eosinophils were uncommon (8.1%) The predominantly histiocytic reaction combined with interface dermatitis was the main inflammation pattern (37.9%). Most biopsies showed more than one reaction pattern. Interface involvement was observed in 64.8%, despite the intended depth of standard tattoo procedures, in which pigment is placed deeper, in the upper- and mid-dermis. Statistical analyses showed a significant association between inflammation severity and pigment depth (P = 0.024). In 6 cases (8.1%) pigments could not be retrieved histologically. CONCLUSIONS: In this cohort we demonstrated that cutaneous reactions to red tattoo ink are frequently characterized by the combination of dermal predominantly histiocytic infiltrates and epidermal interface dermatitis. Allergic reactions to red tattoo pigments probably represent a combination of a subtype IVa and IVc allergic reaction. Clinicians should be aware of the specific histopathology of these reactions and therefore the importance of taking a diagnostic skin biopsy.

The limited value of sentinel lymph node biopsy in lentigo maligna melanoma: A nomogram based on the results of 29 years of the nationwide dutch pathology registry (PALGA).

BACKGROUND: Lentigo maligna melanoma (LMM) predominantly presents in the head and neck of the elderly. The value of sentinel lymph node biopsy (SLNB) for LMM patients remains to be determined, as the reported average yield of positive lymph nodes is less than 10%. In this nationwide cohort study, we wanted to identify LMM patients with an increased risk of SLNB-positivity. METHODS: LMM with an SLNB indication according to the 8th AJCC melanoma guidelines were retrospectively identified from the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). A penalized (LASSO) logistic regression analysis was performed to determine the optimal combination of clinicopathological factors to predict a positive SLNB. RESULTS: Between 1991 and 2020, 1989 LMM patients met our inclusion criteria. SLNB was performed in 16.7% (n = 333) and was positive in 7.5% (25/333). The false-negative rate was 21.9%. Clinically detectable regional lymph node (LN) metastases were found in 1.3% (n = 25). Clinicopathological characteristics best predictive for SLNB-positivity (Odds ratio; 95% CI) were age (0.95; 0.91-0.99), ulceration 1.59 (0.44-4.83), T4-stage (1.81; 0.43-6.2), male sex (1.97; 0.79-5.27), (lymph)angioinvasion (5.07; 0.94-23.31), and microsatellites (7.23; 1.56-32.7) (C-statistic 0.75). During follow-up, regional LN recurrences were detected in 4.2% (83/1989) of patients, of which the majority (74/83) had no evidence of regional LN metastases at baseline. CONCLUSION: Our findings confirm the limited SLNB-positivity in LMM patients. Based on the identified high-risk clinicopathological features, a nomogram was developed to predict the risk of a positive SLNB.

A Low-Grade Trichoblastic Carcinoma Treated with Mohs Micrographic Surgery.

Trichoblastomas are rare dermal neoplasms usually found on the scalp and face. Histology shows a proliferation of small basaloid cells arranged in cords or fields surrounded by cellular stroma. Trichoblastomas are usually not aggressive, but trichoblastic carcinomas arising from preexisting trichoblastomas have been described and have been linked to basal cell carcinoma. We found a tumor with features of trichoblastoma with presence of Merkel cells, but with a deeply infiltrative growth pattern into the fat and muscle tissue, without significant architectural or cellular atypia. Tumors with similar growth patterns were previously described as deeply invasive trichoblastic neoplasms. It appears to be a new entity that has been described before but has not been fully characterized: low-grade trichoblastic carcinoma. This malignancy seems to show only locally aggressive growth. Radical excision was accomplished with Mohs micrographic surgery.

Quantitative molecular detection of minimal residual head and neck cancer in lymph node aspirates.

PURPOSE: Staging of the clinically N(0) neck in patients with head and neck squamous cell carcinoma (HNSCC) using ultrasound-guided, fine needle aspiration cytology (USgFNAC) has a false-negative rate of approximately 20% that might be caused by inaccurate cytology. Molecular analysis of aspirate residues might reduce the false-negative rate, and we therefore set up a quantitative reverse transcription-PCR (Q-RT-PCR) assay based on TaqMan technology using the squamous cell-specific antigen E48 (Ly-6D) as molecular marker. EXPERIMENTAL DESIGN: The detection limit of the assay was determined in reconstruction experiments. The sensitivity of the assay was tested on cytological tumor-positive aspirate residues and the specificity on lymph node aspirate residues of noncancer controls. Subsequently, 235 lymph node aspirate residues of 64 HNSCC patients staged with USgFNAC were examined for the presence of E48 mRNA. E48 Q-RT-PCR results of the aspirated lymph nodes were compared with cytology and clinical outcome. RESULTS: The detection limit of E48 Q-RT-PCR was a single tumor cell in a background of 10(6) peripheral blood mononuclear cells. From the 41 aspirates that were not evaluable at cytology, 24 (59%) could be diagnosed with E48 Q-RT-PCR. In the 191 aspirates that were tumor negative or not evaluable at cytology, 8 samples from 6 patients were E48 positive. These results were confirmed by histology or clinical outcome in 3 of 6 patients. E48 Q-RT-PCR showed an increase in sensitivity from 56 to 67% and an increase in frequency of reached diagnosis from 97 to 100% compared with cytology. The specificity decreased from 100 to 92%. CONCLUSIONS: Real-time E48 Q-RT-PCR is an accurate technique for squamous cell detection in lymph node aspirates of HNSCC patients. The assay shows an increase in sensitivity and frequency of reached diagnosis compared with cytology. The test could be implemented routinely in USgFNAC to diagnose cases for which cytological examination is not conclusive.