Lynch Syndrome and Multiple Primary Tumors Case Study

These flashcards cover key concepts and findings related to Lynch syndrome and the case of a patient with multiple primary tumors.

What is Lynch Syndrome?

An autosomal dominant disorder caused by germline mutations in DNA mismatch repair genes associated with an increased risk of several cancers.

What percentage of colorectal cancers is attributed to Lynch Syndrome?

Approximately 5-8% of all colorectal cancers.

What defines multiple primary tumors?

The simultaneous or metachronous occurrence of two or more primary tumors in one or more tissues and organs in the same individual.

What are the two classifications of multiple primary tumors based on timing?

Simultaneous multiple primary cancers (within 6 months) and metachronous multiple primary cancers (more than 6 months apart).

What is the first diagnosed tumor type in the featured patient's case?

Adenocarcinoma of the left colon.

What genetic mutation was confirmed in the patient through NGS testing?

A germline deletion in exon 12 of MSH2, indicating Lynch syndrome.

What was the eighth primary tumor diagnosed in the featured patient?

A malignant peripheral nerve sheath tumor.

What factor significantly contributes to the long-term survival of cancer patients?

Regular screenings and proactive healthcare management.

What unusual finding was noted in the patient's case related to Lynch syndrome?

The occurrence of a malignant peripheral nerve sheath tumor, which had not been previously reported in association with Lynch syndrome.

What is a common outcome for patients with MLH1 mutations in Lynch syndrome?

They have a high risk of developing various tumors.

What is the recommended frequency for colonoscopy surveillance in Lynch Syndrome patients?

Every 1-2 years, starting at age 20-25.

What are common methods for diagnosing prostate cancer?

Common methods for diagnosing prostate cancer include a digital rectal exam (DRE), prostate-specific antigen (PSA) blood test, ultrasound, and biopsy of prostate tissue.

What does a high PSA level indicate?

A high PSA level may indicate the presence of prostate cancer, but can also be caused by benign conditions such as prostatitis or benign prostatic hyperplasia (BPH).

What is the role of a biopsy in diagnosing prostate cancer?

A biopsy involves taking small samples of prostate tissue to be examined under a microscope for cancer cells, providing a definitive diagnosis.

What are the primary treatment options for localized prostate cancer?

Primary treatment options for localized prostate cancer include active surveillance, surgery (prostatectomy), and radiation therapy.

What is active surveillance in prostate cancer?

Active surveillance is a treatment approach where the patient's cancer is monitored regularly through PSA testing and other evaluations, delaying definitive treatment unless the cancer shows signs of progression.

What are the side effects of prostate cancer treatments?

Side effects of prostate cancer treatments can include urinary incontinence, erectile dysfunction, changes in libido, and fatigue, depending on the treatment method used.

What is hormone therapy in the context of prostate cancer treatment?

Hormone therapy for prostate cancer aims to lower testosterone levels or block its effects on cancer cells, as many prostate cancers rely on testosterone for growth

What is genetic testing, and how is it performed?

Genetic testing is a medical test that analyzes an individual's DNA to identify genetic variations or mutations. This typically involves collecting a blood or saliva sample and analyzing the genetic material using various techniques, including Next-Generation Sequencing (NGS), which allows for rapid sequencing of large amounts of DNA, or targeted gene panels focusing on specific genes related to hereditary conditions.

What can genetic testing results reveal about a person's health?

Genetic testing results can reveal the presence of genetic mutations that may increase an individual's risk for developing certain conditions, such as hereditary cancers or genetic disorders. For example, tests might identify mutations in genes like BRCA1 and BRCA2, indicating a higher predisposition to breast and ovarian cancer.

What is the role of Next-Generation Sequencing (NGS) in genetic testing?

Next-Generation Sequencing (NGS) is a high-throughput method that allows for the simultaneous sequencing of multiple genes or whole genomes. NGS can provide comprehensive genetic information efficiently, making it ideal for identifying mutations associated with various diseases, including multiple cancer types and genetic syndromes, enhancing precision medicine approaches.

What is the significance of immunohistochemistry (IHC) in genetic testing?

Immunohistochemistry (IHC) is a laboratory technique used to detect specific proteins in tissue samples using antibodies. In the context of cancer diagnosis and treatment, IHC can help identify biomarkers indicative of certain tumor types, guiding treatment decisions, such as determining eligibility for targeted therapies based on the presence of specific proteins.

what is a characteristic of LS?

microsatiellete instability

what is MSH2 gerlimine deletion

A germline deletion in exon 12 of MSH2 was detected, with a high tumor mutational burden

of 139.1 mutations/MB, confirming the diagnosis of Lynch syndrome.

what did is the outcome of genetic testing results

patient recieved pembrolizumah (PD inhibitor) cobined with anlotinib hydroclordie whihc normalized psa levels

what does sarcoma mean?

type of cancer that develops in the body's connective tissues, such as bone, muscle, fat, cartilage, and blood vessels

explain how to read a pedigree

A pedigree is a diagram that shows the occurrence and appearance of phenotypes of a particular gene or organism and their ancestors over generations. It is used to track genetic diseases and inheritance patterns across family members.

how to read:

• circles: Represent females.

  •Squares: Represent males.

  •Shaded Symbols: Indicate individuals affected by the trait being tracked.

  • Unshaded Symbols: Indicate individuals who do not have the trait.

  • Horizontal Line: Connects a male and female symbol, indicating a mating or marriage.

  • Vertical Line: Connects a parent to their offspring, showing a parent-child relationship.

  • Sibship line: A line connecting offspring of the same parents

  Roman Numerals: Represent generations (e.g., I, II, III).

  Arabic Numerals: Identify individuals within each generation (e.g., I-1, II-2).

why was the patient a rare case of LS?

due to the eight malignant peripheral nerve sheath tumors diagnosed in the patient, which is uncommon for those with Lynch Syndrome.

what contributed to the patients survival

annual screenings

define malignant periperal nerve sheath tumors

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that originate from the cells surrounding peripheral nerves. They are often associated with neurofibromatosis type 1 and can cause significant morbidity due to their invasive nature.

what did NGS sequecing reveal?

revealed 41 tumor specfic mutations such as NF1 and TP53 mutations , loss of CDKN2A expression and germilne deletion in exon 12 of MSH2 with high tumor mutational burden

what was MMR portein posititve and negative for in immunohistochemistry

MMR protein immunohistochemistry was positive for MLH1 and PMS2 but negative for MSH2 and MSH6, confirming LS-associated malignant peripheral nerve sheath tumor