HY USMLE Q #1035 – Pathology

Mehlmanmedical

14 Aug 202404:13

Summary

TLDRThis educational video script discusses a pathology case of a 7-year-old boy with Burkitt lymphoma, characterized by a 'starry sky' appearance in histopathology due to tingible body macrophages engulfing apoptotic B cells. The script clarifies common misconceptions about the disease's presentation and emphasizes the importance of recognizing the 814 translocation associated with Burkitt lymphoma, contrasting it with other lymphomas and leukemias, such as follicular lymphoma and APL. It concludes with a call to action for viewers to support more content creation.

Takeaways

🔬 The pathology image described is indicative of Burkitt lymphoma, characterized by a 'starry sky' appearance due to the presence of basophilic background of B cells and pale, larger cells which are tingible body macrophages.
📚 Tingible body macrophages are known to engulf apoptotic B cells, which is an important histological feature to recognize in Burkitt lymphoma.
🧬 The t(8;14) translocation is associated with Burkitt lymphoma, involving the c-Myc gene, a transcription factor, and is a key genetic abnormality to know for exams.
❌ The script clarifies that t(14;18) translocation is incorrect for Burkitt lymphoma; instead, it is associated with follicular lymphoma and involves an anti-apoptotic molecule, BCL2.
📈 Follicular lymphoma often presents as a waxing and waning painless neck mass and is the most common indolent (slow-growing) non-Hodgkin lymphoma.
🧬 The t(15;17) translocation is associated with acute promyelocytic leukemia (APL), also known as AML type M3, and involves the PML-RARA gene fusion.
💊 All-trans retinoic acid is a treatment for APL, highlighting the importance of knowing therapeutic options for specific genetic abnormalities in leukemia.
🧬 The Philadelphia chromosome, or t(9;22) translocation, results in the BCR-ABL fusion protein and is associated with chronic myeloid leukemia (CML), a high-yield topic for medical exams.
📝 The script emphasizes the importance of understanding the genetic abnormalities and their clinical correlations for various types of lymphoma and leukemia, which are crucial for medical examinations.

Q & A

What is the most likely diagnosis for a 7-year-old boy with a one-month history of generalized Abdus, fatigue, and a 2 cm mass left of the umbilicus?
-The most likely diagnosis, based on the description and biopsy findings, is Burkitt lymphoma, which is characterized by a starry sky appearance with basophilic background of Burkitt B cells and tingible body macrophages.
What does the term 'starry sky' appearance refer to in the context of Burkitt lymphoma?
-The 'starry sky' appearance refers to the characteristic histological feature of Burkitt lymphoma where pale-staining macrophages are scattered among darker staining lymphoma cells, resembling stars in the sky.
What is the significance of tingible body macrophages in Burkitt lymphoma?
-Tingible body macrophages are significant because they indicate the presence of apoptosis within the tumor. These macrophages engulf and digest apoptotic Burkitt B cells, contributing to the 'starry sky' appearance.
What is the role of apoptosis in Burkitt lymphoma despite it being a hyper-proliferating cancer?
-Even though Burkitt lymphoma is a rapidly proliferating cancer, there is still cell turnover occurring, leading to apoptosis. This process is highlighted by the presence of tingible body macrophages that phagocytose apoptotic B cells.
What is the significance of the 814 translocation in Burkitt lymphoma?
-The 814 translocation is significant as it is almost always associated with Burkitt lymphoma and involves the c-Myc gene, a transcription factor that plays a role in the pathogenesis of the disease.
How does the presentation of Burkitt lymphoma differ from that of follicular lymphoma?
-Burkitt lymphoma often presents with abdominal masses, while follicular lymphoma typically presents as a waxing and waning painless neck mass over one to two years. Follicular lymphoma is also associated with a 14;18 translocation involving the BCL2 gene.
What is the treatment implication of the 15;17 translocation in acute promyelocytic leukemia (APL)?
-The 15;17 translocation in APL results in the fusion of the PML and RARA genes, leading to the production of a PML-RARA fusion protein. All-trans retinoic acid can be used as a treatment to differentiate the leukemic cells.
What is the Philadelphia chromosome associated with, and what is its clinical significance?
-The Philadelphia chromosome is associated with a 9;22 translocation, leading to the fusion of the BCR and ABL genes. This fusion protein, BCR-ABL, is a constitutively active tyrosine kinase, driving the pathogenesis of chronic myeloid leukemia (CML).
Why is it important to know the difference between the translocations associated with Burkitt lymphoma and follicular lymphoma?
-Knowing the difference between the translocations for Burkitt lymphoma (8;14) and follicular lymphoma (14;18) is important for accurate diagnosis and treatment planning, as they involve different genes and have distinct clinical presentations and outcomes.
What is the significance of the term 'indolent' when describing non-Hodgkin lymphomas?
-The term 'indolent' refers to a slow-growing, less aggressive form of non-Hodgkin lymphoma, such as follicular lymphoma. These types of lymphomas often have a more chronic course and may require different treatment approaches compared to more aggressive forms.

Outlines

00:00

🔬 Burkitt Lymphoma Pathology Discussion

The paragraph discusses a case of a 7-year-old boy with a one-month history of generalized Abdus, fatigue, and weight loss, leading to the discovery of a 2 cm mass in the abdomen. A biopsy of this mass reveals a 'Starry Sky' appearance, characteristic of Burkitt lymphoma. The discussion highlights the presence of basophilic (purple/blue) background of Burkitt lymphoma B cells and tingible body macrophages, which are known to engulf apoptotic B cells. The video script emphasizes the importance of recognizing the 814 translocation associated with Burkitt lymphoma and the c-Myc gene, which is a transcription factor. It contrasts Burkitt lymphoma with follicular lymphoma, which is associated with a 148;18 translocation and involves an anti-apoptotic molecule, BCL2. The script also touches upon other lymphomas and translocations, such as APL (acute promyelocytic leukemia) with a 1517 translocation and CML (chronic myeloid leukemia) with a 922 translocation involving the BCR-ABL fusion protein.

Mindmap

Keywords

💡Burkitt Lymphoma

Burkitt Lymphoma is a type of non-Hodgkin lymphoma, characterized by the rapid growth of abnormal B-cells. It is often associated with a translocation involving chromosomes 8 and 14, which leads to the overexpression of the c-MYC oncogene. In the script, Burkitt Lymphoma is described by its characteristic 'starry sky' appearance under the microscope, featuring basophilic (purple/blue) background of Burkitt cells and tingible body macrophages that engulf apoptotic Burkitt cells.

💡Tingible Body Macrophages

Tingible body macrophages are a distinctive feature of Burkitt Lymphoma, where they are seen engulfing apoptotic Burkitt cells, giving the 'starry sky' appearance. These macrophages are named 'tingible body' due to their role in clearing dead cells in the tumor microenvironment. The script highlights the importance of recognizing these cells in the diagnosis of Burkitt Lymphoma.

💡Apoptosis

Apoptosis is a process of programmed cell death that is a normal part of an organism's life cycle, removing harmful, unneeded, or otherwise damaged cells. In the context of Burkitt Lymphoma, despite the hyperproliferation of cancer cells, apoptosis still occurs, and tingible body macrophages are responsible for clearing these apoptotic cells. The script mentions apoptosis as a key feature observed in the biopsy of the mass.

💡Translocation

Translocation in the context of the script refers to a genetic abnormality where parts of chromosomes are broken off and reattached to other chromosomes. This can lead to the activation of oncogenes, such as the c-MYC gene in Burkitt Lymphoma, which is associated with the 8;14 translocation. The script explains that Burkitt Lymphoma is almost always associated with the 8;14 translocation involving the c-MYC gene.

💡Follicular Lymphoma

Follicular Lymphoma is another type of non-Hodgkin lymphoma, characterized by a waxing and waning painless neck mass that can persist for one to two years. It is associated with a 14;18 translocation and overexpression of the BCL2 gene, which is anti-apoptotic, leading to the accumulation of neoplastic cells. The script contrasts Burkitt Lymphoma with Follicular Lymphoma, highlighting the differences in presentation and genetic abnormalities.

💡BCL2

BCL2 is a gene that encodes an anti-apoptotic protein. Overexpression of BCL2, often due to the 14;18 translocation, is associated with Follicular Lymphoma. The script mentions BCL2 as an example of an anti-apoptotic molecule, which is significant in the pathogenesis of Follicular Lymphoma.

💡Hodgkin Lymphoma

Hodgkin Lymphoma is a separate category of lymphoma characterized by the presence of Reed-Sternberg cells. The script briefly mentions Hodgkin Lymphoma to contrast it with non-Hodgkin lymphomas like Burkitt and Follicular Lymphoma, emphasizing the differences in pathology and presentation.

💡Acute Promyelocytic Leukemia (APL)

APL, also known as AML type M3, is a subtype of acute myeloid leukemia characterized by the 15;17 translocation and the fusion of the PML and RARA genes. The script mentions APL as an example of a different type of cancer with a distinct genetic abnormality and treatment approach, highlighting the diversity within hematological malignancies.

💡Philadelphia Chromosome

The Philadelphia Chromosome is a genetic abnormality resulting from a translocation between chromosomes 9 and 22, leading to the fusion of the BCR and ABL genes. This fusion protein is an oncogenic tyrosine kinase, which is associated with Chronic Myeloid Leukemia (CML). The script uses the Philadelphia Chromosome as an example of a translocation that is not related to Burkitt Lymphoma but is significant in another type of leukemia.

💡Indolent Lymphoma

Indolent Lymphoma refers to a slow-growing, less aggressive form of non-Hodgkin lymphoma, such as Follicular Lymphoma. The term 'indolent' implies a 'lazy' or less active behavior of the cancer cells. The script uses this term to describe Follicular Lymphoma, contrasting it with the more aggressive Burkitt Lymphoma.

💡African Boy with Jaw Lesion

This phrase is used in the script to describe a common presentation of Burkitt Lymphoma, particularly in endemic areas where it is associated with Epstein-Barr virus infection. The jaw lesion is a typical site for Burkitt Lymphoma to manifest, although the script also notes that it can present as intraabdominal lymphoma.

Highlights

A seven-year-old boy presents with a one-month history of generalized Abdus, fatigue, and weight loss.

Vital signs are normal, and a palpable 2 cm mass is found on the left of the abdomen.

Biopsy of the mass reveals a starry sky appearance, characteristic of Burkitt lymphoma.

The presence of basophilic background with tingible body macrophages indicates Burkitt lymphoma.

Tingible body macrophages are known to phagocytose B cells undergoing apoptosis in Burkitt lymphoma.

Burkitt lymphoma is associated with an 814 translocation involving the c-Myc gene.

Follicular lymphoma is contrasted with Burkitt lymphoma, being associated with a 148;18 translocation and bcl2 gene.

Follicular lymphoma often presents as a waxing waning painless neck mass over one to two years.

Burkitt lymphoma can present with intraabdominal or jaw lesions, causing kyus accumulation.

Burkitt lymphoma is a high-grade, aggressive B-cell non-Hodgkin lymphoma.

Follicular lymphoma is the most common indolent (slow-growing) non-Hodgkin lymphoma.

Hodgkin lymphoma is characterized by the presence of Reed-Sternberg cells.

Acute promyelocytic leukemia (APL) is associated with a 15;17 translocation and the PML-RARA gene fusion.

APL can be treated with all-trans retinoic acid as well as standard AML therapy.

The Philadelphia chromosome, a 9;22 translocation, is associated with a BCR-ABL fusion protein in chronic myeloid leukemia (CML).

BCR-ABL is an oncogenic tyrosine kinase, a key factor in the development of CML.

Understanding the translocations and gene fusions is crucial for diagnosing and treating various types of lymphoma and leukemia.