On the Acceptance of "Fake" Histopathology: A Study on Frozen Sections Optimized with Deep Learning.

BACKGROUND: The fast acquisition process of frozen sections allows surgeons to wait for histological findings during the interventions to base intrasurgical decisions on the outcome of the histology. Compared with paraffin sections, however, the quality of frozen sections is often strongly reduced, leading to a lower diagnostic accuracy. Deep neural networks are capable of modifying specific characteristics of digital histological images. Particularly, generative adversarial networks proved to be effective tools to learn about translation between two modalities, based on two unconnected data sets only. The positive effects of such deep learning-based image optimization on computer-aided diagnosis have already been shown. However, since fully automated diagnosis is controversial, the application of enhanced images for visual clinical assessment is currently probably of even higher relevance. METHODS: Three different deep learning-based generative adversarial networks were investigated. The methods were used to translate frozen sections into virtual paraffin sections. Overall, 40 frozen sections were processed. For training, 40 further paraffin sections were available. We investigated how pathologists assess the quality of the different image translation approaches and whether experts are able to distinguish between virtual and real digital pathology. RESULTS: Pathologists' detection accuracy of virtual paraffin sections (from pairs consisting of a frozen and a paraffin section) was between 0.62 and 0.97. Overall, in 59% of images, the virtual section was assessed as more appropriate for a diagnosis. In 53% of images, the deep learning approach was preferred to conventional stain normalization (SN). CONCLUSION: Overall, expert assessment indicated slightly improved visual properties of converted images and a high similarity to real paraffin sections. The observed high variability showed clear differences in personal preferences.

Clinicopathological characteristics of thyroid cancer in the federal state of Salzburg.

OBJECTIVE: The aim of our investigation was to evaluate the clinicopathological characteristics and mutation patterns in newly diagnosed cases of thyroid cancer in the federal state of Salzburg, Austria, in the year 2013. METHODS: The medical records of all patients newly diagnosed with thyroid cancer in 2013 in the federal state of Salzburg were retrospectively reviewed. The clinicopathological characteristics and mutations of thyroid cancers were analyzed. RESULTS: 63 patients (mean age: 51.0 years, range: 21-81 years; female 75%, male 25%) were identified. 53 patients had papillary (12 follicular variant), 4 patients follicular (1 oxyphilic variant), 3 patients medullary, and 3 patients anaplastic thyroid cancer. T1 tumors were found in 34 patients (pT1a, 20 patients; pT1b, 14 patients), T2 tumors in 10 patients, T3 tumors in 16 patients, and T4 tumors in 3 patients. Lymph node involvement was seen in 15 patients and metastatic disease in 1 patient. Mutations of BRAF (B-type Raf kinase) were detected in 23 and mutation of NRAS (Neuroblastoma RAS Viral Oncogene Homolog) in 2 papillary thyroid cancers. No concomitant mutations of BRAF and NRAS were found. CONCLUSION: Females accounted for 75% of the patients with newly diagnosed thyroid cancer and the incidence peaked at a younger age than in males. Papillary thyroid cancer was the most frequent tumor type, accounting for 84% of the cases. A high frequency of T1 tumors and cancers with no lymph node involvement was found. Males had a higher proportion of large tumors and more aggressive forms of thyroid cancer than females. Mutations (mostly of BRAF) were found in 47% of the cases. Neither mutations of KRAS (Kirsten rat sarcoma viral oncogene homologue) nor concomitant mutations of BRAF and NRAS were found.

Gemcitabine with cyclosporine or with tacrolimus exerts a synergistic effect and induces tolerance in the rat.

BACKGROUND: This study investigated the effect of the antineoplastic agent gemcitabine (dFdC) in combination with cyclosporine (CsA) or with FK506 on acute heart allograft rejection in a rat model. METHODS: Transplantations were performed in the fully allogeneic Lewis-to-Brown Norway strain combination. dFdC, CsA, and FK506 single-drug therapy and combinations of dFdC with CsA and FK506 were administered at various dosages starting on day 1 to prevent and on day 4 to treat acute rejection until day 20. Animals who did not reject their graft were intraperitoneally injected with 108 splenic donor-type lymphocytes. In addition, Lewis and third-party skin grafts were transplanted to these animals. RESULTS: Mean graft survival times under CsA, FK506, and dFdC monotherapy were 18.3/63.7 days (1 mg/5 mg per kg), 41.7 days, and 24.7/38.7 days (100 microg/150 microg per kg), respectively. CsA and FK506 in combination with dFdC prolonged graft survival to more than 100 days (CsA) and more than 95.2 days (FK506). Graft survival after treatment of an ongoing rejection was 21.5/38.3 days for CsA (1 mg/5 mg per kg) and 17.7/59.2 days for dFdC (100 microg/150 microg per kg). The combination of CsA+dFdC prompted indefinite survival of five of six hearts. Lymphocyte inoculation did not induce graft rejection. Notably, none of the Lewis, but all third-party, skin grafts were rejected immediately. Histomorphologic analysis of grafted hearts, however, demonstrated typical features of chronic rejection. CONCLUSIONS: The combination of CsA and FK506 with low-dose dFdC exerts a synergistic effect in the prevention and treatment of acute allograft rejection in this model. Although chronic rejection could not be prevented, strain-specific tolerance was achieved. Therefore, combining standard immunosuppressants with dFdC is a novel, promising strategy for prevention and treatment of acute allograft rejection.

Primary gastric follicular lymphoma with parafollicular monocytoid B-cells and lymphoepithelial lesions, mimicking extranodal marginal zone lymphoma of MALT.

The incidence of B-cell non-Hodgkin lymphomas (B-NHL) at nodal and extranodal sites is fairly different. Follicular lymphomas (FL) occur predominantly at nodal sites and rarely in the gastrointestinal tract, while marginal zone lymphomas (MZL) of the mucosa-associated lymphatic tissue (MALT) type predominate in the digestive organs and especially in the stomach. We report a 72-year-old female patient admitted for gastroscopy because of epigastric pain. The antral biopsies showed dense lymphocytic infiltrates, partially forming follicles with widened marginal zones and monocytoid cells. Multiple lymphoepithelial lesions (LEL) were also observed. A MZL of the MALT type was suspected morphologically. Immunohistochemical analysis revealed the lymphatic infiltrates to be CD20, bcl-2, bcl-6 and CD10 positive, and negative for CD43, CD5 and cyclin D1. PCR-based analysis showed a JH/bcl-2 rearrangement, corresponding to the translocation t(14;18). An extranodal FL mimicking MZL was diagnosed. The present case is remarkable, as it demonstrates that the detection of LEL and monocytoid B-cells, although suggestive for MZL, is not entirely specific and can also be observed in FL. Pathologists should be aware of this diagnostic pitfall in classifying gastric B-NHL. In equivocal cases, a careful morphological examination, supported by specific immunohistochemical and molecular findings, should lead to the correct diagnosis.

Metallothionein expression in normal, hyperplastic, and neoplastic thyroid follicular and parafollicular C cells using monoclonal antimetallothionein antibody E9.

Metallothioneins (MTs) are a set of ubiquitous low molecular proteins with a high affinity for metal ions, such as zinc, copper, and cadmium. MT overexpression can be induced by these metal ions as well as by other endogenous and exogenous factors. In this study, normal, hyperplastic, and neoplastic thyroid tissues of both follicular and C-cell origin were immuno-histochemically investigated with a monoclonal antibody against I- and II-isoforms of MTs. MT immunoreactivity was demonstrated in the follicular epithelium of 19 normal thyroid glands and in all 32 cases of Graves' disease investigated; 26 of 30 follicular adenomas and 25 of 28 follicular carcinomas showed MT immunoreactivity, whereas only 7 of 20 papillary carcinomas were MT-positive (p < 0.0001 ). In 3 of the 7 positive samples, positivity was restricted to follicular areas of differentation. No MT could be immunolocalized in normal and hyperplastic C cells and medullary thyroid carcinomas (n = 20). In mixed medullary-follicular carcinomas (n = 4), MT staining patterns resembled those seen for thyroglobulin. In anaplastic carcinomas, MTs were mainly immunolocalized in nonspindle cell areas. MT expression in thyroid tumors may reflect the different biological behavior of follicular and papillary carcinomas. Antibodies to MTs may also serve as fairly specific immunohistochemical markers of follicular cell differentiation in thyroid neoplasia.