A 34-year-old man with an unremarkable past medical history is evaluated for an enlarged lymph node in his anterior cervical chain that measures 4 cm in diameter. The patient first felt the lymph node several weeks ago and states that it has been steadily increasing in size. He is concerned about whether or not he "has cancer." The patient is referred to a specialist for surgical removal of the enlarged node. Biopsy reveals abnormal lymph node architecture and numerous lymphocytes. Which of the following, if present, would be most consistent with malignancy in this patient?

Question

A 34-year-old man with an unremarkable past medical history is evaluated for an enlarged lymph node in his anterior cervical chain that measures 4 cm in diameter.  The patient first felt the lymph node several weeks ago and states that it has been steadily increasing in size.  He is concerned about whether or not he "has cancer."  The patient is referred to a specialist for surgical removal of the enlarged node.  Biopsy reveals abnormal lymph node architecture and numerous lymphocytes.  Which of the following, if present, would be most consistent with malignancy in this patient?

Quizplus · Accepted Answer

Lymphadenopathy can represent inflammatory changes within the lymph node (reactive hyperplasia) or malignant transformation. Reactive hyperplasia is a broad term that encompasses all benign, reversible enlargement of the lymphoid tissue secondary to an antigenic stimulus. The nodal response to antigenic stimuli is highly variable and can be classified as follicular hyperplasia, sinus hyperplasia, or diffuse hyperplasia. Follicular hyperplasia occurs when the follicles increase in size and number, whereas sinus hyperplasia occurs when the sinuses enlarge and fill with histiocytes. Diffuse hyperplasia is observed when the nodal architecture is diffusely effaced by sheets of lymphocytes, immunoblasts, and macrophages. When malignant transformation occurs (as in lymphomas), the normal lymph node architecture is distorted or effaced by the proliferation of malignant lymphoid cells, often to a greater extent than that seen with reactive hyperplasia. Malignancy-associated effacement of nodal architecture may be follicular or diffuse. Reactive lymphoid hyperplasia is polyclonal in that it consists of a proliferation of many different cell types within the lymph node. For each type of lymphocyte responding to an antigenic stimulus, multiple genetically-distinct cells of that variety undergo limited monoclonal expansion, leading to an overall polyclonal response. Malignant transformation, in contrast, is monoclonal in that it results from the unchecked proliferation of a single genetically unique cell from only one cell line. Evaluation for monoclonality of the lymphocyte population is important when lymphoma is suspected. The clonality of a T-cell population is assessed by molecular methods, such as PCR, that examine the rearrangement of T-cell receptor (TCR) genes. If a single allele for the V region of the T-cell receptor predominates in a lymphocytic population, monoclonal proliferation is suspected. The same principle applies when assessing B-cell clonality. Monoclonal rearrangement of the genes for immunoglobulin variable regions is suggestive of a B-cell lymphoma. Of the choices given, monoclonal TCR gene rearrangement is most indicative of malignant processes, especially in the context of appropriate clinical features (i.e., weight loss, night sweats, fever, anorexia). (Choices A, B, & C) Pleomorphism, increased mitoses, and nuclear changes are all commonly seen in the lymphocytes of a reactive hyperplastic lymph node. These findings do not automatically classify the specimen as malignant. (Choice E) An admixture of several lymphoid cell types in a lymph node is suggestive of a benign process. A predominantly monomorphic cell population is indicative of malignancy and is characteristic of non-Hodgkin's lymphoma. Hodgkin's lymphoma does demonstrate an admixture of several lymphoid cell types within the lymph nodes; however, this finding does not distinguish Hodgkin's lymphoma from reactive hyperplasia. Additionally, genetic analysis of Reed-Sternberg cells most often reveals monoclonal characteristics. Educational objective: Benign lymph node enlargement in response to antigenic stimulation is associated with a polyclonal proliferation of lymphocytes. A monoclonal lymphocytic proliferation is strong evidence of malignancy. __________ References: Resolving T-cell receptor clonality in two and genotype in four multiplex polymerase chain reactions. (http://www.ncbi.nlm.nih.gov/pubmed/16266900) The polymerase chain reaction in the demonstration of monoclonality in T cell lymphomas. (http://www.ncbi.nlm.nih.gov/pubmed/8543629)

A 34-Year-Old Man with an Unremarkable Past Medical History Is