Index
It can be caused by infection or irritation if diagnosed on a Pap test. In utero, it is more likely to be precancerous.
Atypia (from the Greek, a + typos, without type, a condition of being irregular or non-standard) is a pathological term for a structural abnormality in a cell; it is used to describe atypical cells.
It may or may not be a precancerous indication associated with a subsequent malignancy, but the appropriate level of concern largely depends on its diagnosis context.
For example, differentiated and specialized cells, such as epithelia showing “cellular atypia,” are much less likely to become problematic [cancerous/malignant] than myeloid progenitor cells of the immune system.
The “reverse” in an already specialized and differentiated cell lineage is probably the most troublesome cellular atypia. This is due to the attribution of such atypia to progeny cells further down the line of that cell type.
In current practice, microscopic analysis of the hematoxylin and eosin-stained section is the backbone of diagnosing breast cancer and other cancers.
Traditionally, pathologists examine histological slides under a microscope and make diagnostic decisions. This practice produces subjective results.
The definition of ‘atypia’ has been a controversial issue in pathology, not restricted solely to the genitourinary subspecialty.
The lack of consensus on one of the most used terms in pathology can be attributed to various causes, such as the subjective nature of the histological evaluation, institutional bias, previous diagnosis, and the preference of the evaluating pathologist.
In addition, some pathologists have used the terms “atypia” and “dysplasia” interchangeably, introducing clinical management problems.
Efforts are currently underway to develop technology and systems that allow automated image analysis and machine learning techniques in classification cells showing atypia.
Dysplasia is related to a developmental abnormality and includes abnormalities on larger histopathologic scales.
Uses of the term
The term “atypical” was introduced by the founder of modern cyst diagnosis, Dr. George N. Papanicolaou, to convey a very low suspicion of (pre) malignancy.
Despite controversies over its ambiguous and imprecise definition and its uncertain optimal use, the term “atypia” has continued to be used in cytopathology. It has recently been increasingly used in standardized non-gynecologic cytopathology diagnostic reporting terminology.
Its increasing use suggests that “atypia” remains a proper category to fill the gap between what we can recognize as entirely usual (including reactive changes) and what we can realize as abnormal (premalignant or malignant).
However, this diagnosis should be used parsimoniously, as possible overuse of ‘atypia’ diagnoses can erode clinicians’ confidence in cytopathology, their misunderstanding of the cytopathology report, and increase uncertainty. Diagnosis by physicians with negative consequences on the satisfaction and well-being of patients and the costs of medical care.
A clinically significant standardized cytodiagnostic category of ‘atypia’ requires a narrow definition, quantitative criteria, agreed reference images, a clear clinical meaning (probability of underlying malignancy or premalignancy), and, ideally, well-defined management options.
Implementing a standardized diagnostic category of “atypia” requires ongoing education of cytology professionals and quality control efforts to monitor its use.
The interobserver variability and possible overuse of the ‘atypia’ diagnosis can be reduced by considering and addressing the main factors involved in its variable use, namely the quality of the sample and the definition of ‘atypia,’ the education/training of the patient. Cytologist/pathologist and ‘suprastatic’ factors related to the cytologist/pathologist.
The behavior of atypical cells
Typically, urothelial cells contain oval nuclei, finely stippled chromatin, and tiny or absent nucleoli, as well as extensive cytoplasm and distinct cell membranes.
Even within the spectrum of “normal” cells, urothelial cells are allowed to have certain variations in cell size and cytoplasm, particularly in the most superficial layer of the urothelium ( umbrella cell layer ), which is in constant contact with the contents of the urothelium—urinary space.
These umbrella cells tend to be larger than cells in the intermediate and basal layers, with occasional binucleation and abundant eosinophilic cytoplasm.
To further complicate matters for the pathologist, bladder distention can flatten the surface (or umbrella) cells to a point where the layer can be challenging to identify microscopically.
While atypia often refers specifically to cytological (cellular) abnormalities, architectural changes can also guide the pathologist to the appropriate diagnosis.
Differences between atypia and dysplasia
It is implied that atypia represents a benign process in many cases. At the same time, dysplasia describes a preneoplastic/neoplastic process, although variation in the definition of these categories at the microscopic level often leads to confusion.
From a histological perspective, “atypia” refers to the presence of one or more cellular or architectural features that deviate from that of an otherwise normal cell or group of cells.
Atypia in breast biopsy: what does it mean?
The breasts are made up of lobes, which produce milk, and ducts, which carry milk to the nipple. Two layers of cells line the lobes and ducts.
When the cells that line the lobes or ducts grow, the collection of cells is called hyperplasia. Habitual hyperplasia does not present any risk, but it can become problematic when cells grow irregularly.
This irregular pattern is known as atypia. Atypical cells are not cancerous, but they will increase the patient’s risk of developing cancer in his lifetime.
Atypical ductal hyperplasia affects the ducts of the breast tissue, and atypical lobular hyperplasia, also known as atypical lobular hyperplasia, affects the lobes of the breast tissue.
When the pathologist observes atypical ductal hyperplasia or atypical lobular hyperplasia on a core needle biopsy performed for an abnormal mammogram or ultrasound, an open surgical biopsy may be recommended.
This recommendation is that core needle biopsy specimens can potentially miss a breast cancer 10-20% of the time.
The atypia found in an open surgical biopsy does not require another operation. Still, it will help evaluate cancer and estimate a patient’s risk of developing breast cancer in the future.
Other forms of abnormal cells include intraepithelial neoplasia, also called intraepithelial neoplasia, and lobular carcinoma in situ, called lobular carcinoma.
Atypical ductal hyperplasia and atypical lobular hyperplasia will increase the risk of developing breast cancer four times, and intraepithelial neoplasia and lobular carcinoma in situ will lead to a 10-fold risk of developing breast cancer.
For those at high risk for breast cancer, additional enhanced breast MRI screening tests and medications such as tamoxifen, anastrozole (Arimidex), or Evista (raloxifene) may be considered reduce the risk of breast cancer.
By knowing the results of your pathology from your breast biopsies, you can understand your risk of developing breast cancer and participate in creating a follow-up plan that is best for you.
Reactive urothelial atypia
Reactive urothelial atypia remains one of the broadest categories used to describe abnormal-appearing urothelium, but it is generally considered a benign process at the time of diagnosis.
Reactive atypia is most often diagnosed in an acute and chronic inflammatory process that can arise in previous instrumentation, infection, previous treatment, and other clinical scenarios that incite inflammation.
The cytological and architectural abnormalities in these settings are generally mild and uniform.
Nuclear enlargement, the appearance of vesicular chromatin, and precise nucleoli are the most common features identified microscopically with reactive changes, often occurring in the presence of an inflammatory infiltrate within the urothelium.
A key distinction for reactive atypia is the uniformity of findings throughout the specimen. Pleomorphism (variation in nuclear size), hyperchromasia, and atomic crowding are characteristics that should raise concern for a probable neoplastic or preneoplastic process.
Atypia of unknown meaning
“Atypia of unknown significance” is a term introduced by the International Society for Urological Pathology consensus group in 1998 to classify histological findings that meet various criteria for both reactive changes and dysplasia.
Typically, this diagnosis is used in the setting of reactive nuclear and cytoplasmic changes with mild degrees of pleomorphism and hyperchromasia that are of concern for dysplasia.
Furthermore, this term has been used to describe histological findings in which the level of atypia is disproportionately higher than expected for the amount of inflammation. There is an ongoing debate about whether this term is even an appropriate diagnosis.
Classification of histologic findings as “atypia of unknown significance” ensures clinical follow-up, ideally in the setting of resolved inflammation.
