Posted in Histopathology, Molecular pathology, WEEKLY QUIZZES

MOLECULAR PATHOLOGY QUIZ

MOLECULAR PATHOLOGY QUIZ.

USEFUL FOR

  1. NEET-SS/ DM- Oncopathology/ DM Histopathology
  2. Oncopathology Fellowships
  3. FRCPath- Histopathology and
  4. American Board of anatomic and clinical pathology
  5. Various other boards.

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Posted in Molecular pathology

Tumors characterized by loss of SMARCB1/INI1

SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) is a Protein Coding gene.

Tumors associated with SMARCB1 can be due to it’s complete loss, mosaic expression and reduced expression.

*TUMORS ASSOCIATED WITH COMPLETE LOSS OF SMARCB1

*TUMORS ASSOCIATED WITH MOSAIC EXPRESSION OF SMARCB1

*REDUCED EXPRESSION OF SMARCB1GROUP

Tumors characterized by SMARCB1/INI1 loss

TUMORS ASSOCIATED WITH COMPLETE LOSS OF SMARCB1

1. Atypical/Teratoid rhabdoid tumor: An atypical teratoid rhabdoid tumor (AT/RT) is a rare tumor usually diagnosed in childhood. Although usually a brain tumor, AT/RT can occur anywhere in the central nervous system (CNS), including the spinal cord. About 60% will be in the posterior cranial fossa (particularly the cerebellum). Almost all tumors show complete loss of SMARCB1/INI1.

2. Epithelioid sarcoma: Epithelioid sarcoma is a type of soft tissue sarcoma that typically appears in the extremities (especially in the arms and hands). It also can develop in the main part of the body. It can affect both children and adults, but is most common in young adulthood. Complete loss of SMARCB1/INI1 is found in 70-100% cases.

3. Renal medullary carcinoma: Renal medullary carcinoma, also known as RMC, is a rare cancer of the kidney that predominantly afflicts young people of African descent who carry the sickle cell trait, sickle cell disease, or other sickle hemoglobinopathies that can cause sickling of the red blood cells.

4. Extra skeletal myxoid chondrosarcoma: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue malignancy that is distinguished from other sarcomas by its unique histology and a characteristic chromosomal translocation, typically t(9;22)(q22;q12. 2), fusing EWSR1 to NR4A3. In extraskeletal myxoid chondrosarcomas without NR4A3 fusion, tumors may harbor loss of SMARCB1 (INI1) by loss of function mutation or gene deletion. Extraskeletal myxoid chondrosarcomas without EWSR1-NR4A3 fusion may exhibit rhabdoid morphology and high grade pathological features.

5. Malignant chordoma: Chordoma is a slow growing cancer of tissue found inside the spine. Chordoma can happen anywhere along the spine. It is most often found near the tailbone (called a sacral tumor) or where the spine meets the skull (called a clival tumor). Chordoma is also called notochordal sarcoma. Pediatric chordomas are commonly associated with SMARCB1/ INI1 loss.

6. Sinonasal basaloid carcinoma: Sinonasal basaloid carcinoma occurs in relatively younger patients but over a wide age range, and shows a variable but distinctive growth pattern associated with subtle rhabdoid cells and complete loss of nuclear SMARCB1/INI1. This pattern represents a distinctive variant of sinonasal basaloid carcinoma, described as “SMARCB1(INI1)-deficient basaloid carcinoma.”

Here is mnemonic for you

TUMORS ASSOCIATED WITH MOSAIC EXPRESSION OF SMARCB1

1. Schwannomatosis- SMARCB1 mutations are found in a significant proportion of schwannomatosis patients, and an even higher proportion of rhabdoid patients. Familial schwannomatosis, which is associated with SMARCB1/INI1 loss.

2. Gastrointestinal stromal tumor (GIST)- Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that can be located in any part of the digestive system. Their most common sites are the stomach and small intestine.

3. Ossifying fibromyxoid tumor- Ossifying fibromyxoid tumor (OFMT) is a distinctive mesenchymal neoplasm of uncertain differentiation, with cords, nests, clusters and sheets of uniform ovoid cells embedded in a variable myxoid, fibromyxoid or hyalinized stroma, often with an incomplete peripheral shell of bone

REDUCED EXPRESSION OF SMARCB1 GROUP

1. Synovial sarcoma– Synovial sarcoma is classified as a tumor of uncertain differentiation, and some synovial sarcomas have rhabdoid cells.

SOME TUMOR SYNDROMES ASSOCIATED WITH SMARCB1

  1. Rhabdoid Tumor predisposition syndrome and
  2. Coffin -sirs syndrome.

Watch a quick video summary here

Reference: Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Kenichi kohashi and Yoshinao oda.

Posted in Histopathology, Molecular pathology

Molecular pathology of ADIPOCYTIC TUMORS

Molecular pathology of ADIPOCYTIC TUMORS – based on WHO 2020 Soft tissue and bone tumors.

LIPOMAS

The pathogenesis of lipomas is related to reactivated expression of the HMGA2 protein, which plays a role in the development of the mesodermal lineage during embryogenesis

  1. ANGIOLIPOMA– The majority (80%) have been reported to have low-frequency PRKD2 mutations.
  2. CHONDROID LIPOMA– is characterized by a recurrent t(11;16) (q13;p13) chromosomal translocation.
  3. SPINDLE CELL/PLEOMORPHIC LIPOMA: is characterized 13q deletions /RB GENE.
  4. MYOLIPOMA: Cytogenetic alterations of the HMGA2 gene have been reported in a few cases

LIPOSARCOMA

  1. Atypical lipomatous tumour/well differentiated liposarcoma: characterized by supernumerary ring and giant marker chromosomes,containing amplified sequence of MDM2
  2. DEDIFFERENTIATED liposarcomaAmplified MDM2
  3. MYXOID LIPOSARCOMA– Translocations producing FUS-DDIT3 or rarely EWSR1-DDIT3 fusion transcripts are pathognomonic
  4. PLEOMORPHIC LIPOSARCOMA: Complex karyotypes. . The most frequent mutations involve TP53 and NF1.

OTHER ADIPOCYTIC TUMORS

  1. HIBERNOMA: Cytogenetically, almost all hibernomas have breakpoints in chromosome arm 11q, with a distinctive clustering to 11q13.
  2. LIPOBLASTOMA: The most common numerical change is one or more extra copies of chromosome 8, with or without concurrent rearrangement of 8q11-q13

VIEW THE SHORT VIDEO FOR A QUICK SUMMARY

Posted in Molecular pathology

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.

Click below for a quick summary

Posted in Female genital pathology, Histopathology, Molecular pathology

Molecular pathogenesis of ovarian epithelial tumors.

Molecular progression of serous ovarian tumor. Borderline low and high grade

1.Molecular progression of low grade ovarian serous tumors.
There is data to suggest progression from serous cystadenoma / cystadenofibroma with BRAF / KRAS mutations → SBT (serous borderline tumor) → LGSC (Low grade serous carcinoma) ; however, this is still controversial

2. Molecular progression of high grade serous ovarian tumors.

TP53 alterations in nearly all cases of high grade serous carcinoma

Germline, somatic or promoter hypermethylation (inactivation) of BRCA1 and BRCA2 in ~50% of cases