Conditions associated with DICER- 1 syndrome

DICER-1 SYNDROME IS A Rare Autosomal Dominant cancer syndrome Caused by inactivating germline mutations in genes encoding DICER-1. It is an RNase involved in the generation of mature miRNA.

CONDITIONS ASSOCIATED WITH DICER-1 SYNDROME.

1. PLEUROPULMONARY BLASTOMA:

  • Type I tumors are cyst -like tumors in the lung. They are most common in children aged 2 years and younger and have a good chance of recovery. …
  • Type II tumors are cyst-like with some solid parts. These tumors sometimes spread to the brain or other parts of the body.
  • Type III tumors are solid tumors

2. OVARIAN SERTOLI- LEYDIG CELL TUMOR:

Sertoli-Leydig cell tumor (SLCT) is a rare cancer of the ovaries. The cancer cells produce and release a male sex hormone called testosterone. The exact cause of this tumor is not known

3. CYSTIC NEPHROMA OF KIDNEY:

Cystic nephroma is a rare kidney neoplasm belonging to the entity of cystic tumours. It is a slow-growing tumour, which develops insidiously, sometimes reaching a considerable size. The diagnosis is more often accidental (except for mass syndrome in children). It is a benign tumour that may be treated by partial sparing nephrectomy

4.MULTINODULAR GOITRE:

Multinodular Goiter (MNG) is defined as the special condition of thyroid glands, where there are multiple lumps (nodules) formed.

5. PITUTARY TUMOR:

Pituitary tumors are abnormal growths that develop in your pituitary gland. Some pituitary tumors result in too much of the hormones that regulate important functions of your body. Some pituitary tumors can cause your pituitary gland to produce lower levels of hormones.

6. OCULAR MEDULLOBLASTOMA:

Medulloblastoma is the commonest childhood malignant central nervous system tumour. It occurs in the midline of the cerebellum

7. EMBRYONAL RHABDOMYOSARCMA:

Embryonal rhabdomyosarcoma (ERMS) ERMS usually affects children in their first 5 years of life, but it can occur at older ages as well. ERMS tends to occur in the head and neck area, bladder, vagina, or in or around the prostate and testicles.

8.PINEALOBLASTOMA:

Pineoblastoma is more aggressive than other types of pineal gland tumors. Its fast growth usually causes cerebrospinal fluid (CSF) to build up in the brain. This condition is called hydrocephalus. While pineoblastoma may spread through the CSF in 10% to 20% of cases, most of the time the tumors do not spread to other parts of the body.

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VITAL, SUPRAVITAL AND INTRAVITAL STAINING

Vital, supravital and intravital staining are three different types of staining techniques. However, vital and supravital terms are often used interchangeably.

Let’s look at some of the major differences in staining between the three and why these terms shouldn’t be used interchangeably.

1. VITAL STAINING

1.Contrary to the name, vital stains are taken up by dead cells and not by living  cells.


2. Demonstration of  nuclear staining using a vital stain signifies cells death, because living cells are impermeable to the stain.


3. Example: Tryptan blue and propiodine iodine

VITAL STAINS ATE TOO BULKY OR TOO CHARGED THEY CANNOT ENTER LIVE CELLS- Hence only stain dead cells.

Vital, supravital and intravital staining are three different types of staining techniques. However, vital and supravital terms are often used interchangeably.  Let’s look at some of the major differences in staining between the three and why these terms shouldn’t be used interchangeably.  1. VITAL STAINING  1.Contrary to the name, vital stains are taken up by dead cells and not by living  cells.   2. Demonstration of  nuclear staining using a vital stain signifies cells death, because living cells are impermeable to the stain.   3. Example: Tryptan blue and propiodine iodine  VITAL STAINS ATE TOO BULKY OR TOO CHARGED THEY CANNOT ENTER LIVE CELLS- Hence only stain dead cells.   VITAL STAINS 2. SUPRAVITAL STAINS  1. Supravital staining is a method of staining used in microscopy to examine living cells that have been removed from an organism.  2. Those that enter and stain living cells are called supravital stains     3. Examples New Methylene Blue and Brilliant Cresyl Blue for reticulocyte staining.   Reticulocyte stained SUPRAVITAL stain 3. INTRAVITAL STAIN  1. Intravital staining of living cells is done by injecting the dye into any part of the animal body (either intravenous, intraperitoneal or subcutaneous), producing specific coloration of certain cells, particularly those of the reticulo-endothelial system.  2. Common dyes used are lithium, carmine and India ink.
Vital stains

2. SUPRAVITAL STAINS

1. Supravital staining is a method of staining used in microscopy to examine living cells that have been removed from an organism.

2. Those that enter and stain living cells are called supravital stains

3. Examples New Methylene Blue and Brilliant Cresyl Blue for reticulocyte staining.

Reticulocyte stained SUPRAVITAL stain

3. INTRAVITAL STAIN

1. Intravital staining of living cells is done by injecting the dye into any part of the animal body (either intravenous, intraperitoneal or subcutaneous), producing specific coloration of certain cells, particularly those of the reticulo-endothelial system.

2. Common dyes used are lithium, carmine and India ink.

There you go!! Hope the confusion is cleared.

For multiple choice questions on staining

Check below for a quick summary.

Some gastrointestinal pathogens and their differentiating features.

Gastrointestinal pathogens are very common in routine practice. It takes experience and keen observation to differentiate gastrointestinal pathogens from one another. In case of confusion, go with your ‘GUT’ feeling.

Lets look at a few differentiating features of Giardia lamblia, Cryptosporidium parvum and Isospora belli.

  1. GIARDIA LAMBLIA:

Pear shaped trophozoites with 2 ovoid nuclei, present in the luminal surface. They are 10-15 microns in length and 5-9 microns in width.

GIARDIA IS SEEN IN THE LUMINAL SURFACE

CRYPTOSPORIDIUM IS SEEN ATTACHED TO ENTEROCYTES LIKE SMALL BEADS.

2. CRYPTOSOPORIDIUM PARVUM

In tissue biopsies, 2 – 5 μm basophilic round bodies are seen protruding from the apex of enterocytes (“blue beads”) within the cell membrane. Parasites bulge out of apex of epithelial cells

ISOSPORA IS LARGEST AMONG THE THREE. IN CONTRAST TO GIARDIA AND CRYPTOSPORIDIUM – ISOSPORA DOES NOT HAVE AN APICAL LOCATION, INSTEAD LOCATED IN THE TIP OF VILLI.

3. ISOSPORA BELLI

Oocysts are generally ovoid to ellipsoid in shape, range from 10-40µm in length by 10-30µm in width. Cysts are present in PARASITO-
PHOROUS VACUOLE. Does not have an apical location.

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Tumors showing TRK (tropomyosin receptor kinase) gene fusion

Recent molecular studies have revealed that,  several tumors harbor TRK fusion. However fusion frequencies vary. 

Several NTRK1/2/3 (neurotrophic tyrosine receptor kinase) fusions have been reported. It is important to identify them since they serve as potential targets for therapy

The NTRK1, 2, and 3 genes encode a family of tyrosine kinase receptors with an active role
in neural development.

They are encoded by three different NTRK genes:

1. NTRK1 located on chromosome 1q21-q22 – corresponding receptor TrkA binds to NGF (nerve growth factor)

2. NTRK2 on chromosome 9q22.1- corresponding receptor TrkB binds to BDNF (brain derived natriuretic factor)

3. NTRK3 on chromosome 15q25- corresponding receptor TrkC.

NTRK oncogenic fusions can be encountered in two main different scenarios:

  1. Consists of rare tumors in which NTRK fusions are found at very high frequencies, as dominant oncogenes.
  2. Comprises common tumors in which NTRK fusions are identified at low frequencies, including both solid and hematological malignancies.

Here are a few tumors with high frequency TRK gene fusion – [ETV6-NTRK3 fusion]  – t(12;15)

1.Mammary analogue secretory carcinoma (MASC)- >75%-  Some MASC harbour ETV6- RET fusion -t(10;12)- They have poor outcome since they are non-responsive to TRK fusion therapy.

2.Secretory carcinoma of breast- >75%

3. Cellular and mixed mesoblastic nephroma (>75%)

4. Infantile fibrosarcoma. >75%

5. Ossifying renal tumor of infancy

DIAGNOSIS :  As yet, there are no FDA-approved NTRK gene fusion tests.

IHC : Pan-Trk IHC has the power to become an incredibly rapid and efficient screening tool for NTRK rearrangements.

NGS : Molecular methods like NGS and reverse transcription polymerase chain reaction (RT-PCR) provide a more comprehensive look at the NTRK genes, these tests are expensive and slow, potentially delaying treatment.

TREATMENT: Entrectinib and Larotrectinib are TRK inhibitors

Other tumors with NTRK fusion  partners is shown below.

NTRK gene fusions in cancers.  Partners of NTRK1, NTRK2, and NTRK3 are stratified according to the cancer
type where they are most frequent. Reference: doi:10.3390/ijms21100000

Reference: Federica Zito Marino et.al. NTRK Fusions, from the Diagnostic Algorithm to Innovative Treatment in the Era of Precision Medicine. Int. J. Mol. Sci. 2020, 21, 0.

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