Benign Normal Tissue Mimicking Neoplastic Disorders: A Cytopathological Review

Knowledge of normal morphology is an essential prerequisite for interpreting pathological changes. We are very familiar with normal tissue histology, which is already taught in medical schools. In contrast, information on the normal appearance of tissue in cytological specimens, particularly fine-needle aspiration biopsy (FNAB), is not widely available. A lack of familiarity with normal cytology is an easily avoidable source of diagnostic errors or difficulties. This is especially true during rapid on-site evaluation (ROSE), where misinterpretation of normality can lead to the procedure being finished prematurely. In addition, there are tissues whose normal cytomorphology is rarely seen and with which pathologists and cytotechnicians are largely unfamiliar. In addition to its significant practical utility, normal cytomorphology constitutes an important independent field of knowledge within the realm of diagnostic cytopathology.

A review has been conducted of situations in which cytological normality can lead to diagnostic confusion. The review discusses the most well-known and frequent potential errors, such as those related to the bronchial, duodenal, and gastric mucosa (echoendoscopic FNAB), mesothelium, liver, pancreas, bone marrow, cerebellum, etc. In addition, we have emphasized the more complex cases, even if they are rare. Among these are the spleen, kidney, neural ganglia, seminal vesicle, testis, and pineal gland.

There are several reasons why understanding normal cytomorphology is becoming increasingly important. During the sampling of small tumors, the needle frequently penetrates the surrounding parenchyma, aspirating normal tissue cells. FNAB of deep and technically complex lesions increases the likelihood of contamination from surrounding tissues. In addition, the emergence of new approaches such as echoendoscopy involves examining tissues that were rarely seen before. If we add this to the speed required during ROSE, the need for an in-depth understanding of normal cytomorphology becomes obvious. Given the wide variety of tissues, a general analysis is not possible; it must be conducted on an individual basis. In any case, cytomorphology of normal tissues is typically striking and characteristic, which facilitates their recognition. This review aimed to assist by presenting common and uncommon normal morphology and key points for specific recognition.