Perineural differentiation in neurotized nevi.

BACKGROUND: Perineuriomatous melanocytic nevi are rare and this may indicate the similar embryological source of melanocytes and peripheral nerves in the neural crest. Neurotized melanocytic nevi may resemble nerve sheath tumors histologically, and show schwannian differentiation. However, literature on whether neurotized nevi differentiate into perineural cells is controversial. We examined our cases of neurotized nevi for evidence of perineural differentiation. MATERIALS AND METHODS: A total of 100 benign nevi with large neurotized component (microscopically involved a low power field 4.2 mm in diameter) were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for EMA, Claudin1, Glut1 and neurofilament were performed. RESULTS: Perineural differentiation was immunohistochemically detected in the neurotized component of the nevi in 61% of the cases with EMA and in all the cases with Glut1 and Claudin1. Axonal differentiation was not detected with neurofilament. The expression pattern, especially with Glut1, was usually in form of partial or complete staining surrounding the Meissner's corpuscle-like structure (MCLS). Also, a linear/curvilinear staining pattern was observed particularly with Claudin1. A diffuse staining pattern with EMA, Glut1 and Claudin1 was detected in a case with a microscopically distinct whorl structure, and in which spindle cells are separated from the superficial epithelioid melanocytes with an abrupt transition histologically. These findings of the case are compatible with previous reports of perineuromatous nevus. CONCLUSION: Perineural differentiation is not uncommon and immunohistochemically observed in all nevi with a relatively large component of neurotization. To prevent misdiagnosing desmoplastic melanoma and overtreating patients, it is crucial to be aware of perineuromatous nevi.

Dermatoscopic Characteristics, Lesional Capillaroscopic Features, and Histopathological Correlation of Small Plaque Parapsoriasis and Mycosis Fungoides.

INTRODUCTION: Dermatoscopy is a frequently used non-invasive diagnostic procedure. OBJECTIVES: Considering that mycosis fungoides (MF) mimics parapsoriasis clinically in early stages, we aim to determine the dermatoscopic criteria and the histopathological correlations in patients with MF and small plaque parapsoriasis (SPP). METHODS: This prospective study involved 28 patients with clinical and histopathological diagnoses of MF and 31 patients with SPP. Videodermoscopy and USB capillaroscope were used to evaluate the patients vessels at ×200 magnification. Vascularity was evaluated through microvascular density (MVD) scoring involving CD34 antibody staining. RESULTS: Fifty-nine patients were included in this study. The scores corresponding to the presence of short linear vessels, linear-curved vessels, branching linear vessels, and non- structured orange-colored areas were significantly higher in the MF patients than in the SPP patients (P < 0.05). The highest MVD (P = 0.01) scores were also higher in the MF patients than in the SPP patients. CONCLUSIONS: The SPP and early-stage MF patients differed in their MVD scores, and the findings correlated with the dermatoscopy and lesional capillaroscopy findings. Differentiating features between SPP and MF were thus identified.

68 Ga-FAPI-04 PET/CT in Selected Breast Cancer Patients With Low FDG Affinity : A Head-to-Head Comparative Study.

PURPOSE: In this prospective study, PET findings of 18 F-FDG PET/CT in breast cancer staging were compared with 68 Ga-FAP inhibitor (FAPI) 04 PET/CT findings in selected cases with relatively low 18 F-FDG uptake in the primary tumor or with suspected nodal or distant metastases. PATIENTS AND METHODS: Twenty-four women with a median age of 45 years (range, 36-67 years) who underwent initial staging 18 F-FDG PET/CT for breast cancer underwent 68 Ga-FAPI-04 PET/CT imaging within the same week. SUV max and quantities of primary tumors and locoregional and distant metastatic lesions were recorded from both images, and these data were compared statistically. RESULTS: The histological subtypes of primary tumors were 11 invasive lobular, 8 invasive ductal, and 5 mucinous subtypes. More intense 68 Ga-FAPI-04 uptake (mean, 17.1 ± 7.9; 7.4-38.5) was detected in all primary tumoral lesions compared with 18 F-FDG (mean, 6.3 ± 3.9; 1.5-20.5) ( P = <0.001, Z = 4.107). Additional lesions showing 68 Ga-FAPI-04 uptake in the breast were detected in 29.2% (n = 7) of patients. In 8.3% (n = 2) of the patients, the primary lesion showed only 68 Ga-FAPI-04 uptake. In 68 Ga-FAPI-04 PET/CT, 25% (n = 6) of the patients showed more lymph node involvement and more intense uptake in the ipsilateral axilla. In addition, infraclavicular (level 3) lymph nodes in 4 patients (16.7%), supraclavicular lymph nodes in 1 patient, and internal mammary lymph nodes in 1 patient were detected only on 68 Ga-FAPI-04 PET/CT. In a patient with lung and bone metastases, 68 Ga-FAPI-04 uptake was higher, and the lung nodule showed only 68 Ga-FAPI-04 uptake. CONCLUSIONS: In selected low-FDG-affinity breast cancer patients, 68 Ga-FAPI-04 PET/CT showed the primary tumor with higher sensitivity and higher SUV max values compared with 18 F-FDG PET/CT. In addition, it is believed that this method may contribute to the management of patients' treatment by increasing the nodal stage.

The roles of 68 Ga-PSMA PET/CT and 18 F-FDG PET/CT imaging in patients with triple-negative breast cancer and the association of tissue PSMA and claudin 1, 4, and 7 levels with PET findings.

AIM: Aim of study is to compare the results of Gallium-68-prostate-specific membrane antigen ( 68 Ga-PSMA) and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography(PET)/computed tomography (CT), to evaluate the correlation between PET findings and the level of PSMA, Claudin (Clau) 1, 4, and 7 receptors obtained by immunohistochemical (IHC) analysis, and to determine potential predictive and prognostic values in TNBC. METHODS: Forty-seven lesions of 42 subjects diagnosed TNBC both underwent PET/CT scan for preoperative staging/restaging were prospectively included study. PSMA, Clau 1, 4, and 7 expressions were IHC evaluated from the biopsy samples of the primary tumor (PT). Maximum standardized uptake value(SUV max) of the PT, lymph node, and distant organ metastases (DOMs) on 18 F-FDG and 68 Ga-PSMA PET/CT were compared with PSMA, Clau 1, 4, and 7 receptor expressions. RESULTS: IHC analyses on 29 BC lesions to demonstrate Clau expression showed 86% (25/29) Clau 1, 86% (25/29) Clau 4, 45% (13/29) Clau 7, and 48% (14/29) PSMA-positive. The mean DOM (SUVmax) was 15.5 ± 11.6 for 18 F-FDG and 6.0 ± 2.9 for 68 Ga-PSMA. Axial diameter of BC PT had a significant positive correlation with 18 F-FDG SUVmax, 68 Ga-PSMA SUVmax, and PSMA scores. BC lesions 68 Ga-PSMA SUVmax had a significant negative correlation with the Ki-67 index. Axial diameter of the primary tumor had significant negative correlation with Clau 7 scores ( r = -0.409, P = 0.034). Absence of Clau 1 expression found to significantly increase the rate of DOM (100% vs. 28%) ( P = 0.014). All patients with axillary lymph node (ALN) metastases ( n = 17, 100%) exhibited Clau 4 positivity ( P = 0.021). The presence of PSMA expression observed to significantly increase the rate of ALN metastases (64.7% vs. 25%) ( P = 0.035). CONCLUSION: Confirming PSMA expression with PET imaging would be significant as PSMA, a theranostic agent, may be a considerable potential agent for radionuclide treatment strategies, in addition to its additional diagnostic contribution to FDG, especially in patients with metastatic TNBC, which is an aggressive, heterogeneous disease.

Increased FDG Uptake in Skin Rashes Caused by EGFR Inhibitors.

ABSTRACT: Most patients treated with epidermal growth factor receptor inhibitors develop cutaneous advance effects. The extent and severity of treatment-related skin rashes are associated with good treatment response and prognosis. Herein, we presented increased uptake of the 18F-FDG in skin rashes after treatment with epidermal growth factor receptor inhibitors in 2 patients diagnosed with metastatic colorectal cancer.

Radiomics of locally advanced rectal cancer: machine learning-based prediction of response to neoadjuvant chemoradiotherapy using pre-treatment sagittal T2-weighted MRI.

PURPOSE: Variable response to neoadjuvant chemoradiotherapy (nCRT) is observed among individuals with locally advanced rectal cancer (LARC), having a significant impact on patient management. In this work, we aimed to investigate the potential value of machine learning (ML)-based magnetic resonance imaging (MRI) radiomics in predicting therapeutic response to nCRT in patients with LARC. MATERIALS AND METHODS: Seventy-six patients with LARC were included in this retrospective study. Radiomic features were extracted from pre-treatment sagittal T2-weighted MRI images, with 3D segmentation. Dimension reduction was performed with a reliability analysis, pair-wise correlation analysis, analysis of variance, recursive feature elimination, Kruskal-Wallis, and Relief methods. Models were created using four different algorithms. In addition to radiomic models, clinical only and different combined models were developed and compared. The reference standard was tumor regression grade (TRG) based on the Modified Ryan Scheme (TRG 0 vs TRG 1-3). Models were compared based on net reclassification index (NRI). Clinical utility was assessed with decision curve analysis (DCA). RESULTS: Number of features with excellent reliability is 106. The best result was achieved with radiomic only model using eight features. The area under the curve (AUC), accuracy, sensitivity, and specificity for validation were 0.753 (standard deviation [SD], 0.082), 81.1%, 83.8%, and 75.0%; for testing, 0.705 (SD, 0.145), 73.9%, 81.2%, and 57.1%, respectively. Based on the clinical only model as reference, NRI for radiomic only model was the best. DCA also showed better clinical utility for radiomic only model. CONCLUSIONS: ML-based T2-weighted MRI radiomics might have a potential in predicting response to nCRT in patients with LARC.

68Ga-DOTA-FAPI-04 PET/CT in Neuroendocrine Carcinoma of the Liver With Elevated AFP Level: Comparison With 18F-FDG PET/CT.

ABSTRACT: A 68-year-old woman with a mass lesion in right hepatic lobe had an elevated α-fetoprotein level (>54,000 ng/mL). The lesion showed higher 68Ga-DOTA-FAPI-04 uptake than 18F-FDG uptake in consecutive PET/CT images. The histopathological examination revealed neuroendocrine carcinoma with Ki-67 proliferation index of 80%.

Tissue eosinophil levels as a marker of disease severity in bullous pemphigoid.

BACKGROUND: Eosinophils play an important role in bullous pemphigoid (BP) pathogenesis. Although tissue infiltration with eosinophils has been known for a long time, there is a lack of knowledge about the relationship between tissue eosinophil levels and disease severity and clinical characteristics of the patients. METHODS: Fifty-nine patients diagnosed with BP between January 2008 and December 2018 were reviewed. Haematoxylin-Eosin (H&E)-stained preparations were re-evaluated in terms of tissue eosinophil levels. For disease severity, Bullous Pemphigoid Disease Area Index (BPDAI) was used. The relationship between tissue eosinophil levels and disease severity and clinical features were evaluated. RESULTS: Erosion/blister and urticaria/erythema BPDAI scores were higher in the group with high tissue eosinophil level than the group with low tissue eosinophil level. Tissue and peripheral blood eosinophil count were correlated with total urticaria/erythema BPDAI scores. There was no correlation between blood and tissue eosinophil count. The mortality rate was 64.7% vs 44.0% in the high vs low tissue eosinophil groups. Tissue eosinophil levels were high in patients with BP accompanying neurological disease. CONCLUSIONS: Tissue eosinophil count and peripheral blood eosinophil count were correlated with disease severity in BP. Tissue eosinophil levels were also high in patients with BP accompanying neurological disease.

68Ga PSMA Uptake at Roux-en-Y Eso-jejunostomy Junction Mimicking the Recurrence of Gastric Carcinoma in PET/CT.

A 67-year-old male patient had undergone total gastrectomy and Roux-en-Y eso-jejunostomy 3 years ago for the treatment of tubular adenocarcinoma located at the corpus of the stomach. The patient was diagnosed with Gleason score 8 (4+4) metastatic prostate cancer during the follow-up period and received hormone therapy. Owing to his elevated prostate-specific antigen levels (77 ng/mL), his clinician referred him gallium-68 (68Ga) prostate-specific membrane antigen 11 (PSMA) positron emission tomography/computed tomography (PET/CT) for restaging. PET/CT showed multiple 68Ga PSMA receptor-positive skeletal lesions and linear PSMA activity at the eso-jejunostomy junction. He was then referred to undergo 18fluorine-fluorodeoxyglucose (18F-FDG) PET/CT to screen for gastric carcinoma recurrence. PET/CT images demonstrated no 18F-FDG avid lesion. However, endoscopy and biopsy performed with samples from the eso-jejunostomy junction revealed superficial benign squamous epithelial fragments.

Palisaded Encapsulated (Solitary Circumscribed) Neuroma: A Review of 30 Cases.

Background. Solitary circumscribed neuroma (SCN), also known as palisaded encapsulated neuroma (PEN), is a benign neural tumor. It may be mistaken as either schwannoma or neurofibroma in pathology practice. In this study, we aimed to define clinicopathologic and immunohistochemical features and discuss its differential diagnosis. Materials and Methods. The histopathological features of 30 cases of SCN/PEN were reviewed. The presence of intralesional axons, Schwann, and perineural cell distributions were investigated by performing neuronal immunomarkers. Results. Twelve cases were females, and 18 cases were males. The mean age was 48 years. Lesions were mostly located on the face (27/30). Histologically, 18 had a lobular pattern, 9 were plexiform, 2 fungating, and 1 multilobular. Although the majority of cases were well circumscribed, capsular integrity was at least focally disrupted (73%). Verocay body was noted only in 6 cases (20%). One case showed excessive hyperkeratosis, forming a keratin horn. Adipocytic change was detected in another case. The lesions consisted of S100-positive Schwann cell proliferation and were partially surrounded by perineural cells highlighted by EMA or Claudin-1. The amount of intralesional axons revealed by neurofilament immunostaining was variable. Conclusion. SCN/PEN is a relatively common lesion, and usually seen as an asymptomatic papule on the face of elderly patients. A circumscribed lesion composed of bundles of bland-looking spindle cells thought to be of neural origin is seen in the dermis. Pathologists should be aware of the existence of plexiform and multilobular PEN/SCN variants, to avoid misdiagnosis of plexiform neurofibroma or schwannoma.

Evaluation of appendiceal mucinous neoplasms with a new classification system and literature review.

Appendiceal mucinous neoplasms constitute a diagnostic spectrum ranging from adenoma to mucinous adenocarcinoma. To date, many classification systems have been proposed to reflect the histomorphological diversity of neoplasms in this range and their clinical correspondence, and also to form a common terminology between the pathologist and clinicians. The aim of this review is to provide an updated perspective on the pathological features of appendiceal mucinous neoplasms. Using the 2016 Modified Delphi Consensus Protocol (Delphi) and the Eighth Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 19 cases presented from June 2011 to December 2016 were evaluated and diagnosed with appendiceal mucinous neoplasia. According to the Delphi, non-carcinoid epithelial tumours of the appendix were categorized in eight histomorphological architectural groups. These groups are adenoma, serrated polyp, low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm, mucinous adenocarcinoma, poorly-differentiated adenocarcinoma with signet-ring, signet-ring cell carcinoma and adenocarcinoma. The most common symptom was right lower quadrant pain. The median age of these cases was 60±15 years. There was a preponderance of females (F/M: 15/4). In our re-evaluation, six cases were diagnosed as serrated polyp. There were 11 cases in the LAMN group and two cases in the mucinous adenocarcinoma group. Using the Delphi and the AJCC manual, there were many changes in the classification, evaluation and treatment of appendiceal mucinous neoplasms. These classification systems have facilitated the compatibility and communication of clinicians and pathologists and have guided clinicians on treatment methods.