Methods for estimating the size/extent of DCIS in specimen.


Why to measure size of DCIS in specimen:

• Higher rates of invasive cancer detected according to DCIS size. 
• Progression to invasive cancer occurred in 10% of DCIS patients with a  DCIS tumor size between 2.5 to 3.5 cms, 57% for tumor size 3.6 to 4.5 cms and 71% for tumors between 4.5 and 6 cms.
• Tumors over 2.5 cms have a higher risk of progressing to invasive cancers.

J Exp Clin Cancer Res. 2006 Jun;25(2):223-7.

There are multiple methods for estimating the extent of DCIS (see Figure):

• DCIS in 1 block: The area involved by DCIS can be measured from a single slide, if DCIS is present in only 1 block. If separate foci are present, the largest distance between foci should be reported. This method will underestimate the extent of DCIS when multiple blocks are involved and should not be used in such cases.

•  Serial sequential sampling: The entire specimen is blocked out in such a way that the location of each block can be determined. The extent of the DCIS can be calculated by using a diagram of the specimen, the thickness of the slices, and the location of the involved blocks.7-9 This method is recommended for all excisions likely to harbor DCIS or with previously diagnosed DCIS (eg, by diagnosis on a prior core needle biopsy).

•  Nonsequential sampling: The number of blocks involved by DCIS is correlated with the extent of DCIS up to 40 mm.8 Multiplying the number of blocks involved by DCIS by the approximate width of a tissue section gives an estimate of the extent. In 2 studies, multiplying by 3 mm underestimated the extent of DCIS, and multiplying by 5 mm may overestimate the extent.8,9 Therefore, multiplying by 4 mm is recommended unless there is additional information that a different number would yield a more accurate result. This method may underestimate extent if not all areas of DCIS are sampled. Therefore, it is recommended that all tissue likely to be involved by DCIS be sampled (eg, all grossly abnormal tissue and all tissue with radiologically suspicious calcifications). When feasible, the entire specimen should be examined microscopically.

• This method may result in a larger estimation of extent than the serial sequential sampling method when DCIS is present in a large volume of tissue in 3 dimensions rather than in a predominantly linear distribution. The best estimate for correlation with outcomes (eg, residual disease or recurrence) will require further studies.

• This method can be applied to any specimen and will give a better estimation of extent than measuring extent on a single slide when multiple blocks contain DCIS.

• • Margins: If DCIS involves or is close to 2 opposing margins, the distance between the margins can be used as the extent of the DCIS within the specimen.

• • Gross lesions: In some cases of high-grade DCIS, there may be a gross lesion that can be measured. Confirmation of the gross size must be confirmed by microscopic evaluation.

• The largest estimate obtained using any of these methods should be used to report the estimated size (extent) of the DCIS.

Pathology, classification, and grading of  neuroendocrine 

tumors arising in the digestive system

The terminology of gastroenteropancreatic (GEP) neuroendocrine neoplasms has evolved over the past two decades to reflect a separation into two major categories:

●Well-differentiated neuroendocrine tumors (NETs) show a solid, trabecular, gyriform, or glandular pattern, with fairly uniform nuclei, salt-and-pepper chromatin, and finely granular cytoplasm. These tumors were traditionally referred to as carcinoid and pancreatic neuroendocrine (islet cell) tumors. Although carcinoid tumors and pancreatic NETs may have similar characteristics on routine histologic evaluation, they have a different pathogenesis and biology.

●Poorly-differentiated neuroendocrine carcinomas, which are high-grade carcinomas that resemble small cell or large cell neuroendocrine carcinoma of the lung . Poorly differentiated neuroendocrine carcinomas are often associated with a rapid clinical course, while well-differentiated NETs generally have a much better prognosis, with an overall five-year survival of approximately 67 percent 

Histologic appearance of the spectrum of neuroendocrine tumors arising in the gastrointestinal tract

Well-differentiated NET shows an organoid pattern and difficult-to-find mitotic activity on H&E stain (panel A),

( Panel C) the proliferative rate (as measured by the Ki67 labeling index) is very low  (<1 percent="" span="">

poorly-differentiated neuroendocrine carcinoma shows frank features of carcinoma with numerous mitotic figures and tumor necrosis on H&E stain (panel B),the Ki67 labeling index is very high (80% in this case) (panel D).

Scientists Convert Human Skin Cells Directly Into Brain Cells

Using a finely tuned cocktail of small molecules, researchers from Washington University in St. Louishave successfully converted adult skin cells into the major type of brain cell affected in the fatal neurodegenerative disorder Huntington’s disease. For the first time, this was achieved without the need to go through a stem cell intermediate, avoiding the production of other types of cell. Importantly, when the researchers transplanted these cells into the brains of mice, they survived and showed similar properties to native cells. While it is still in the early days, these preliminary results could suggest that in the future, this technique may be developed further to help patients with Huntington’s. The work has been published in Neuron.

Huntington’s disease is an inherited brain disorder that causes the progressive degeneration of nerve cells, or neurons. This disease predominantly affects a type of cell called medium spiny neurons (MSNs), which are crucial for movement control. As they are gradually lost in the brain, the patient experiences involuntary muscle movements and cognitive decline. While there is currently no cure, a future possible treatment avenue could involve replacing the lost cells in the brain. But first, researchers need to work out a way to not only produce these cells, but also to ensure they are not rejected by the patient, which is what the Washington University scientists are working towards.

Previous work by this team found that it is possible to turn skin cells into different types of brain cell by exposing them to two small molecules of RNA, a similar molecule to DNA. These specific "microRNAs” unravel target stretches of DNA, or genes, which are responsible for the identity of the cell. In doing so, proteins called transcription factors can access the DNA sequences, which result in the expression of genes which govern the development of neurons. Armed with this knowledge, the researchers added to these cells the same transcription factors present in brain regions containing MSNs. This combination of ingredients was found to result in the direct conversion of skin cells into this specific type of neuron.

“We think that the microRNAs are really doing the heavy lifting,” co-first author Matheus Victor said in a news-release. “They are priming the skin cells to become neurons. The transcription factors we add then guide the skin cells to become a specific subtype, in this case medium spiny neurons. We think we could produce different types of neurons by switching out different transcription factors.”

When the researchers analyzed these reprogrammed cells, they were found to show similar gene expression profiles to human MSNs. Furthermore, after they were transplanted into the brains of mice, they survived for over 6 months, exhibited similar properties to the native MSNs and even connected to distant neuronal targets in the brain.

The researchers are now taking this work one step further by using the same technique on skin cells taken from Huntington’s patients. To investigate whether these cells can alleviate some of the symptoms associated with the disease in animals, the researchers plan to transplant these cells into mouse models of Huntington’s.

Read more at following link

http://www.iflscience.com/brain/scientists-convert-human-skin-cells-directly-brain-cells