Morphometrically estimated variation in nuclear size - A useful tool in grading prostatic cancer

At present there are several grading systems for prostatic carcinoma. Most are difficult to reproduce. An objective method of grading seems to be necessary and could make comparisons between various groups of patients easier and grading more reliable. In the present study morphometrically estimated nuclear size and variation in nuclear size are matched with the survival rates of 207 patients who underwent total perineal prostatetomy for cancer. On the basis of morphometrically estimated variation in nuclear size the patients could be divided into two groups with significantly differing survival rates. In this way it was possible to split the group of patients with grade 2 carcinoma (Mostofi's grading system) into two groups of patients with significantly different survival rates. The survival rates in these two groups did not differ significantly from those in the patients with Grade 1 and Grade 3 tumors respectively. The results are discussed in the light of the recent literature on the subject. Morphometry seems to be a valuable tool in grading prostatic cancer

Higher Grading Generalisations of the Toda Systems

In the present paper we obtain some integrable generalisations of the Toda system generated by flat connection forms taking values in higher ${\bf Z}$--grading subspaces of a simple Lie algebra, and construct their general solutions. One may think of our systems as describing some new fields of the matter type coupled to the standard Toda systems. This is of special interest in nonabelian Toda theories where the latter involve black hole target space metrics. We also give a derivation of our conformal system on the base of the Hamiltonian reduction of the WZNW model; and discuss a relation between abelian and nonabelian systems generated by a gauge transformation that maps the first grading description to the second. The latter involves grades larger than one.Comment: 24 pages, latex, no figures; Expanded version accepted for publication in Nuclear Physics

Cutting out the middleman: measuring nuclear area in histopathology slides without segmentation

The size of nuclei in histological preparations from excised breast tumors is predictive of patient outcome (large nuclei indicate poor outcome). Pathologists take into account nuclear size when performing breast cancer grading. In addition, the mean nuclear area (MNA) has been shown to have independent prognostic value. The straightforward approach to measuring nuclear size is by performing nuclei segmentation. We hypothesize that given an image of a tumor region with known nuclei locations, the area of the individual nuclei and region statistics such as the MNA can be reliably computed directly from the image data by employing a machine learning model, without the intermediate step of nuclei segmentation. Towards this goal, we train a deep convolutional neural network model that is applied locally at each nucleus location, and can reliably measure the area of the individual nuclei and the MNA. Furthermore, we show how such an approach can be extended to perform combined nuclei detection and measurement, which is reminiscent of granulometry.Comment: Conditionally accepted for MICCAI 201

Grading systems for breast carcinoma: comparative study of cytohistological agreement

PURPOSE: to assess the concordance of cytological tumoral and nuclear grading systems on fine needle aspiration biopsies of breast carcinoma with histological specimens and compare them to identify the best results. METHODS: cytohistological agreement was evaluated in a retrospective study of 50 cases of fine needle aspiration biopsies of histologically confirmed invasive ductal carcinoma of the breast, with 5 grading systems being applied for comparative purposes.The classifications were divided according to criteria of tumoral grading (nuclear and architectural criteria - Mouriquand and Guilford systems) and nuclear criteria (Black modified by Fisher (BM), simplified Black system (SB) and Hunt system). The grading systems used for histological analysis were those of Scarff-Bloom-Richardson modified by Elston (SBR modified) for tumor evaluation and the BM systems for nuclear evaluation. RESULT: the cytological grading systems that showed best agreement were BM and SB based on nuclear criteria (anisonucleosis, size, mitosis, and chromatin). Among the cytological grading systems based on nuclear and architectural criteria (combined), Guilford's classification showed the best agreement, possibly due to the larger number of variables used, which permitted a smaller margin of error. CONCLUSION: the methods evaluated in the present study can be considered reasonable as cytological grading systems.OBJETIVOS: avaliar a concordância das classificações citológicas de graduação tumoral e nuclear nos esfregaços de punção aspirativa por agulha fina (PAAF) de carcinoma de mama com os métodos utilizados nos espécimes histológicos e compará-los para identificar aqueles que apresentam melhores resultados. MÉTODOS: a avaliação da concordância cito-histológica foi realizada em estudo retrospectivo de 50 casos de PAAF de carcinoma ductal invasivo de mama, confirmados histologicamente, aplicando-se de forma comparativa cinco sistemas de graduação. As classificações foram separadas segundo critérios de graduação tumoral (critérios nucleares e arquiteturais - sistemas de Mouriquand e de Guilford) e nuclear (sistemas de Black modificado por Fisher - BM, de Black simplificado - BS e de Hunt). As classificações utilizadas na histologia foram os sistemas de graduação de Scarff-Bloom-Richardson modificado por Elston (SBR modificado), para avaliação tumoral, e os de BM, para avaliação nuclear. RESULTADOS: os sistemas de graduação citológica que apresentaram maior concordância foram os sistemas de BM (K=0,358) e BS (K=0,302), baseados em critérios nucleares (anisonucleose, tamanho, mitose e cromatina). Dentre os sistemas de graduação citológica que apresentam critérios nucleares e arquiteturais, a classificação de Guilford demonstrou maior concordância (K=0,260), possivelmente pelo número maior de variáveis utilizadas, possibilitando menor margem de erro. CONCLUSÃO: no presente estudo, estes métodos mostraram-se regulares como sistemas de graduação citológica.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUNIFESP, EPM, Depto. de PatologiaSciEL

Prognostic significance of primary-tumor extension, stage and grade of nuclear differentiation in patients with renal cell carcinoma

Surgery remains the preferred therapy for renal cell carcinoma. The various adjunctive or complementary therapies currently yield disappointing results. Identifying reliable prognostic factors could help in selecting patients most likely to benefit from postoperative adjuvant therapies. We reviewed the surgical records of 78 patients who had undergone radical nephrectomy with lymphadenectomy for renal cell carcinoma, matched for type of operation and histology. According to staging (TNM), 5.1% of the patients were classified as stage I, 51.3% as stage II, 29.5% as stage III and 14.5% as stage IV. Of the 78 patients 40 were T2N0 and 21 T3aN0. Tumor grading showed that 39.7% of the patients had well-differentiated tumors(G1), 41.1% moderately-differentiated (G2), and 19.2% poorly-differentiated tumors (G3). Overall actuarial survival at 5 and 10 years was 100% for stage 1; 91.3% at 5 years and 83.1% at 10 years for stage II; 45.5% and 34.1% for stage III; and 29.1% and nil for stage IV (stage II vs stage III p = 0.0001). Patients with tumors confined to the kidney (pT2N0) had better 5- and 10-year survival rates than patients with tumors infiltrating the perirenal fat (pT3aN0) (p = 0.000006). Survival differed according to nuclear grading (G1 vs G3 ; p = 0.000005; G2 vs G3; p = 0.0009). In conclusion our review identified tumor stage, primary-tumor extension, and the grade of nuclear differentiation as reliable prognostic factors in patients with renal cell carcinomas

Tumor architecture exerts no bias on nuclear grading in breast cancer diagnosis

We recently reported that nuclear grading in prostate cancer is subject to a strong confirmation bias induced by the tumor architecture. We now wondered whether a similar bias governs nuclear grading in breast carcinoma. An unannounced test was performed at a pathology conference. Pathologists were asked to grade nuclei in a PowerPoint presentation. Circular high power fields of 27 invasive ductal carcinomas were shown, superimposed over low power background images of either tubule-rich or tubule-poor carcinomas. We found (a) that diagnostic reproducibility of nuclear grades was poor to moderate (weighed kappa values between 0.07 and 0.54, 27 cases, 44 graders), but (b) that nuclear grades were not affected by the tumor architecture. We speculate that the categorized grading in breast cancer, separating tubule formation, nuclear pleomorphism, and mitotic figure counts in a combined three tier score, prevents the bias that architecture exerts on nuclear grades in less well-controlled situation

Prognostic significance of DNA cytometry in cutaneous malignant lymphomas.

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML

Fine group gradings of the real forms of sl(4,\C), sp(4,\C), and o(4,\C)

We present an explicit description of the 'fine group gradings' (i.e. group gradings which cannot be further refined) of the real forms of the semisimple Lie algebras sl(4,\C), sp(4,\C), and o(4,\C). All together 12 real Lie algebras are considered, and the total of 44 of their fine group gradings are listed. The inclusions sl(4,\C)\supset sp(4,\C)\supset o(4,\C) are an important tool in our presentation. Systematic use is made of the faithful representations of the three Lie algebras by $4\times 4$ matrices.Comment: 19 page

The impact of histopathology and NAB2-STAT6 fusion subtype in classification and grading of meningeal solitary fibrous tumor/hemangiopericytoma.

Meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor with propensity for recurrence and metastasis. Although multiple classification schemes have been proposed, optimal risk stratification remains unclear, and the prognostic impact of fusion status is uncertain. We compared the 2016 WHO CNS tumor grading scheme (CNS-G), a three-tier system based on histopathologic phenotype and mitotic count, to the 2013 WHO soft-tissue counterpart (ST-G), a two-tier system based on mitotic count alone, in a cohort of 133 patients [59 female, 74 male; mean age 54 years (range 20-87)] with meningeal SFT/HPC. Tumors were pathologically confirmed through review of the first tumor resection (n = 97), local recurrence (n = 35), or distant metastasis (n = 1). A STAT6 immunostain showed nuclear expression in 132 cases. NAB2-STAT6 fusion was detected in 99 of 111 successfully tested tumors (89%) including the single STAT6 immunonegative tumor. Tumors were classified by CNS-G as grade 1 (n = 43), 2 (n = 41), or 3 (n = 49), and by ST-G as SFT (n = 84) or malignant SFT (n = 49). Necrosis was present in 16 cases (12%). On follow-up, 42 patients had at least one subsequent recurrence or metastasis (7 metastasis only, 33 recurrence only, 2 patients had both). Twenty-nine patients died. On univariate analysis, necrosis (p = 0.002), CNS-G (p = 0.01), and ST-G (p = 0.004) were associated with recurrence-free (RFS) but not overall survival (OS). NAB2-STAT6 fusion type was not significantly associated with RFS or OS, but was associated with phenotype. A modified ST-G incorporating necrosis showed higher correlation with RFS (p = 0.0006) and remained significant (p = 0.02) when considering only the primary tumors. From our data, mitotic rate and necrosis appear to stratify this family of tumors most accurately and could be incorporated in a future grading scheme