AssessmentsLymphomas: Pathology review
USMLE® Step 1 style questions USMLE
A 46-year-old man comes to his physician for assessment of a pruritic rash for the past two months. The patient states he has tried calamine lotion and several emollients with minimal relief. He has not used any body washes or creams. The patient has a remote history of intravenous drug use but has not used in the past year. Vital signs are within normal limits. Examination reveals a scaly rash over the chest, back, and legs. A photograph of the rash is shown. A biopsy of one of these lesions exhibits clusters of abundant lymphocytic cells with cerebriform nuclei within the epidermis and dermis. Which of the following is the most likely diagnosis?
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Which of the following is the most likely diagnosis?
Content Reviewers:Yifan Xiao, MD
Contributors:Zachary Kevorkian, MSMI, Victoria Cumberbatch, Evan Debevec-McKenney, Jake Ryan, Maria Emfietzoglou, MD
At the family medicine center, there is a 25 year old male, named Hogan, who came in because of a painless non-erythematous mass on his neck. Next to Hogan, there is a 30 year old male immigrant from Africa, named Burak, who has noticed a painless mass on his jaw. He also complains of drenching night sweats, and unexplained weight loss over the last few months. Biopsy is ordered for both people. In Hogan’s there’s binucleated B cells surrounded by mainly lymphocytes. Burak’s biopsy showed numerous lymphocytes with some tingible-body macrophages. CBC is normal for both.
In contrast, non-Hodgkin lymphomas don’t have Reed-Sternberg cells can sometimes spread non-contiguously, and can involve extranodal sites like the skin, gastrointestinal tract, and brain. Non-Hodgkin’s lymphomas can occur in both children and adults. Finally, overall prognosis is better with Hodgkin lymphomas.
Let’s start by looking at Hodgkin lymphoma. This type of lymphoma typically arise from B-cells and spread in a contiguous manner, meaning it spreads to nearby lymph nodes, and rarely involve extranodal sites. It has a bimodal age distribution, affecting young adults in their 20s and adults older than 60 years of age. Histologically, it’s characterized by the presence of Reed-Sternberg cells and for your exams, remember that these are binucleated, neoplastic B cells that look kind of like owl eyes. The large mononuclear version of Reed-Sternberg cells are called Hodgkin cells. These abnormal, neoplastic cells are usually surrounded by non-neoplastic inflammatory cells, mostly T cells, and sometimes eosinophils. They can also activate fibroblasts, which secrete collagen.
Okay, now Hodgkin lymphoma includes two major subgroups, the first and more common is classical Hodgkin lymphoma, or cHL. In classical Hodgkin lymphoma, neoplastic cells don’t express CD45 or CD20, which are seen on normal B-cells, but they do express CD15 and CD30.
Classical Hodgkin lymphoma can be further divided into four histologic subtypes based on the type of inflammatory cells and whether fibrosis is present. Nodular sclerosis is the most common subtype and the neoplastic cells are surrounded by collagen that create nodules. Also, a unique Reed-Sternberg cell, called a lacunar cell can be seen. When the tissue is fixed in formalin, the cytoplasm shrinks and it makes the nucleus look like it’s sitting in the middle of a lake, or lacunae. Now, the second most common subtype is mixed cellularity Hodgkin lymphoma and the neoplasm is mixed with many different types of immune cells like eosinophils, neutrophils, lymphocytes, plasma cells, and histiocytes. The third subtype is lymphocyte-rich Hodgkin lymphoma, and it’s named for having mostly lymphocytes surround the Reed-Sternberg cells. It generally has the best prognosis of all of the classical Hodgkin lymphoma subtypes. The fourth type is lymphocyte-depleted Hodgkin lymphoma, and it’s the least common type. It’s named for the lack of normal lymphocytes and the abundance of Hodgkin and Reed-Sternberg cells. Mixed cellularity and lymphocyte-depleted Hodgkin lymphoma are seen more commonly in immunocompromised patients.
The other major subgroup of Hodgkin lymphoma is nodular lymphocyte predominant Hodgkin lymphoma. In contrast to classical Hodgkin lymphoma the abnormal B cells express CD20 and CD45 on their surface, but don’t have CD15 and CD30. They have a variant of Reed-Sternberg cells called lymphocyte predominant cells. The lymphocyte predominant cells have a lobulated nucleus that looks like popcorn, so they're called “popcorn cells.” It’s also called nodular because a large number of lymphocytes cluster around the popcorn cells, forming nodules.
Alright, now let’s switch gears and talk about non-Hodgkin lymphomas, which can be further subdivided in two main groups, B cell and T cell lymphomas. B cell lymphomas are more common and the neoplastic B cells usually express CD20 on their surface. And there are various types of non-Hodgkin B cell lymphomas and an important feature is how quickly each one grows. They can be indolent, aggressive, or highly aggressive.
Let’s start with B cell lymphomas, and the first one is follicular lymphoma, and it’s usually indolent. The main concept you’ll need to know for the exams is that follicular lymphoma can develop from a chromosomal translocation between chromosome 14 and chromosome 18. In the translocation, the two chromosomes swap large pieces of chromosome with each other. As a result, the BCL2 gene from chromosome 18 is placed on chromosome 14, and this causes an overexpression of bcl-2. Bcl-2 normally blocks cell death, or apoptosis, so overexpression of the bcl-2 gene prevents abnormal cell death. Okay, now, another high yield fact is that, under the microscope, follicular lymphoma is characterized by clusters of packed follicles composed primarily of centrocytes, which are small cleaved cells, and a few centroblasts which are large non-cleaved cells. A helpful clue is that this type of lymphoma often cause waxing and waning painless lymphadenopathy.
The second type of B cell lymphoma is diffuse large B cell lymphoma which shows aggressive growth. This is the most common type of non-Hodgkin B-cell lymphoma in adults and it’s linked with BCL-6 and BCL-2 mutations.
A third type of B cell lymphoma is Burkitt lymphoma, and it’s a highly aggressive lymphoma. Burkitt lymphoma can also result from a chromosomal translocation. In this case, the Myc gene is translocated from chromosome 8 where it ends up on chromosome 14 and again that upregulates its expression. The Myc gene stimulates cell growth and metabolism, so the translocation results in increased cell division. Now, high yield fact that is frequently tested is that Burkitt lymphoma is often associated with Epstein Barr virus, or EBV, infection. EBV infects lymphocytes and can incorporate its DNA into a host cell’s DNA, but exactly how that leads to lymphoma is still unclear. For the exams, you also have to remember that in Burkitt’s lymphoma there is extranodal involvement. In individuals from Africa, Burkitt lymphoma classically causes extranodal involvement of the jaw, while in individuals outside Africa, Burkitt lymphoma classically causes extranodal involvement of the abdomen, most often at the ileocecal junction..
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