Formulating a differential diagnosis begins after evaluation of the topography of the specimen and determination of the disease process. Recognizing an index feature, a morphological characteristic that helps define a disease process more specifically, can be extremely useful in establishing the correct diagnosis. For example, a tumor in the uveal tract composed of atypical cells containing cytoplasmic pigment is suggestive of uveal melanoma, whereas a small, round, blue cell tumor at the posterior pole of the eye of an infant or child is highly suggestive of retinoblastoma. The index feature should differentiate the specimen from others demonstrating the same general disease process. Returning to the example above, both uveal melanoma and retinoblastoma are malignant intraocular tumors, but the former is characterized by atypical pigmented cells while the latter is characterized by small blue cells. Although very basic index features can be recognized without great difficulty, recognition of other index features requires familiarity and experience. For example, the differential diagnosis for a melanocytic proliferation of the conjunctiva includes nevus, primary acquired melanosis, and melanoma. Narrowing the differential diagnosis in this case requires recognition of the key histologic features of each of these entities.
Table 1-2 Classification of Neoplasia
Figure 1-12 General classification and growth patterns of malignant tumors (A) with photomicrographs depicting adenoid cystic carcinoma of the lacrimal gland (B), rhabdomyosarcoma (C), and large B-cell lymphoma (D).
(Illustration by Christine Gralapp; parts B and D courtesy of Vivian Lee, MD; part C courtesy of Nasreen A. Syed, MD.)
If a key index feature is absent, forming a focused differential diagnosis based on the topography of the specimen and the disease process is necessary before a definitive or specific diagnosis can be established. Special stains or other ancillary pathology studies may provide information that focuses the differential. For instance, the differential diagnosis that can be constructed from the features of noncaseating granulomatous inflammation of the conjunctiva includes sarcoidosis, foreign body, and fungal and mycobacterial infections. Some of these entities can be excluded from the differential with the use of special stains for acid fast and fungal organisms.
Readers are encouraged to practice using the hierarchical framework presented in this chapter by reviewing each step in sequence when they examine histologic images and pathologic specimens. Chapters 5 through 15 of this book provide tissue-specific examples of the differential diagnoses for each of the major disease process categories. See Table 1-1 for the expanded organizational paradigm.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.