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See how Isabel performs on these diagnostically challenging cases. The analysis of Isabel's performance includes : Does Isabel suggest the final diagnosis of the case? How many of the MGH differential diagnoses does Isabel suggest?

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A Woman in Her 90s with Unilateral Ptosis. A Year-Old Man with Hypophosphatemia.


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Approach to diagnosis and pathological examination in bronchial Dieulafoy disease: a case series

The center then appears to consist of shrunken lymphocytes, some of which have acentric nuclei and look like plasma cells. This occurs when the technician dries the slide with a hairdryer without putting it into xylene to make the slide clear. The nuclei of the lymphocytes shrink to darkly stained dots that lack any detail, again making an accurate diagnosis difficult Figure 2.

We encountered this problem for several years until Liu et al. Since surgical pathology is part of clinical medicine, one cannot make an accurate lymphoma diagnosis without adequate clinical information. The World Health Organization WHO emphasizes that diagnosis of such pathologies should integrate clinical, morphological, immunophenotypical, and molecular genetic data.

Therefore, regular multidisciplinary discussion plays an important role in the diagnosis of many diseases, especially challenging cases such as lymphomas.

Although current diagnoses are based on combining results from ancillary techniques, the final diagnosis is still the subjective conclusion of a pathologist. Due to variations in training background and practical experience, pathologists sometimes draw different conclusions from the same objective specimen. These discrepancies can delay the proper treatment for patients, and in extreme circumstances can cause legal problems.

As summarized by Bridget S. Wilkins 3 , immunohistochemistry-related errors are shown in Table 1. In our experience, the most common error is insufficient range of antibody tests. With an insufficient range of tests, there may be inadequate diagnostic precision. For example, a splenic mantle cell lymphoma was categorized as marginal zone lymphoma and later diagnosed as DLBCL when the patient developed cervical lymph node enlargement. This misdiagnosis likely occurred because CD5 and Cyclin D1 expression were not initially examined Figure 3. The use of an insufficient panel of immunostains can also cause the misdiagnosis of an ALK positive lymphoma as Hodgkin lymphoma or reactive lymphoid proliferation.

Several outside medical centers were consulted for their opinion on a case and did not include ALK in their initial panel of antibodies Figure 4.


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  • Importance of pathologic examination?

Familiarity with the immunohistochemical staining pattern of the normal lymph node and the variation observed in lymphoma is critical to the accurate diagnosis of lymphoma. Recognizing the different distribution pattern of CD20 and CD3 positive lymphocytes between normal and lymphoma conditions is essential for the correct diagnosis. In addition, B cell lymphoma-2 Bcl-2 positivity in the follicular center must be evaluated by the number and distribution pattern of germinal center T cells.

Pitfalls in the pathological diagnosis of lymphoma

This is critical in differentiating follicular lymphoma from reactive proliferation. Furthermore, Bcl-2 positivity cannot be used to distinguish between follicular lymphoma and other small B cell lymphomas, because all of these conditions may express Bcl It is beneficial for pathologists to understand the specificity of antibodies. For example, it is important to know that a monoclonal antibody has specificity for one epitope on one antigen and not for the entire cell expressing that antigen.

Cross-lineage expression of antigens can occasionally occur, such as aberrant expression of CD20 in T and NK cell lymphomas or CD3 expression in non-T cell lymphomas. Most monoclonal antibodies that are commonly used have been developed with high sensitivity for use with formalin fixed, paraffin-embedded tissues. However, some antibodies stain with less sensitivity than would be expected, and can vary with fixation, so that true positive cells may be missed.

Non-hematolymphoid tumors may express some CD markers, such as CD45, however, this is rarely expressed in carcinomas and sarcomas 4 , 5. Malignant melanoma can be CD56 and CD positive and have an atypical plasmacytoid morphology, which can lead to the misdiagnosis of plasmacytoma.

Moreover, immunohistochemistry is oftentimes laboratory specific, which can explain the variation in immunohistochemical staining between different groups. Therefore, it is essential that a pathologist be familiar with the staining results of a particular laboratory. In addition to immunohistochemistry, flow cytometry is another important tool in diagnostic hematopathology. Flow cytometric immunophenotyping offers the sensitive detection of antigens when antibodies may not be available for formalin fixed paraffin-embedded immunohistochemical immunophenotyping.

However, formalin fixed, paraffin-embedded immunohistochemical immunophenotyping is advantageous because it preserves the architecture of the tissue. Additionally, some antibodies are available for immunohistochemistry and not flow cytometry, allowing for the immunohistochemical evaluation of the expression of the proteins in which these antibodies target. Taken together, these techniques should be used as complimentary tools in diagnostic hematopathology.