INTERPRETATION OF TISSUE CHANGES

            The next step after describing gross anatomic changes is to try to interpret these changes. Many changes that pathologists see when evaluating gross anatomic changes are not important for the disease pathogenesis or diagnosis. The pathologist should be able to recognize not only lesions, but also changes referred to as non-lesions, lesions with little or no clinical and diagnostic significance, and postmortem artifacts. After any gross description and interpretation, you should ask yourself a few questions: Is the tissue change a lesion? If it is, what is its extension within the affected tissue? Is that lesion reversible? Is the affected tissue too vulnerable? Does it regenerate easily? Does it regenerate at all? Is there a “spare” organ to compensate the dysfunction of the affected one? Did the animal have any history of clinical signs related to the particular change? Those simple questions need to be addressed when you are working on the interpretation of your findings. It is important to describe the extension of the pathologic change, for instance “expanding 30-40% of the pulmonary parenchyma there are multifocal to coalescing areas…” You should know that a single granuloma measuring 3 mm in diameter in the caudal pulmonary lobe would likely cause no harm to the individual, but a disseminated metastatic carcinoma composed of hundreds of small nodules measuring 3 mm in diameter throughout the lungs will cause respiratory collapse and death. The capacity for reversibility of a pathologic change is determined by its nature (degeneration, infection, neoplasia, etc.). For instance, a focal area of bacterial dermatitis in a dog is probably harmless…treatment is relatively easy. Not good news for a patient with cutaneous lymphoma. The vulnerability of a particular tissue is associated with the redundancy of its anatomic units, its functional reserve, and its capacity of regeneration. The hepatic parenchyma is composed of hundreds of thousands of redundant anatomic units (lobules), making the loss of some of these lobules not important for the organism. On the other hand, there is no such luxury in the brain, where the impairment or loss of a tiny portion of the delicate parenchyma could lead to a permanent dysfunction or total loss of function of a wide range of vital elements. The functional reserve of an organ is related to the presence of inactive anatomic units that become available and functional after an insult. The power or capacity of regeneration diminishes the vulnerability of an organ. The liver can regenerate up to 70% of its parenchyma; on the other hand, there is not so much room for regeneration for lesions in the central nervous system.

            The interpretation of tissue changes is the diagnosis. A pathology diagnosis (or morphologic diagnosis) is achieved based on the assessment of gross anatomic changes and/or histology. One can easily formulate a morphologic diagnosis based on a gross change, which is typically referred to as preliminary diagnosis. A preliminary morphologic diagnosis is an interpretation and a brief summary of the gross findings observed during postmortem evaluation. It is usually defined when the pathologist is writing the gross report, and can be adapted, modified, or completely replaced after histologic evaluation of the case is completed. An adequate morphologic diagnosis should include a few essential pieces of information in one sentence: 1) location; 2) age of the lesion; 3) severity; 4) distribution; 4) type of process; and 5) special features. The age of a lesion can be subjective and its correct assessment depends on the clinical history, good gross observations, and professional experience. As we will see later, the age of a lesion is more useful for the diagnosis than for the description itself. Classical terms applied for this classification are acute, subacute, and chronic. Acute changes should be considered when they took a few minutes to a few hours or maybe a couple of days to develop. Thus, a few gross features that may indicate chronicity include cell and tissue proliferation with partial or diffuse increased volume of an organ and deposition of fibrous connective tissue (fibrosis), bone tissue (hyperostosis), or neoplastic cells.

            All of these words can be organized according to your preference, but keep them all in mind, so you will not forget to add each one to the morphologic diagnosis. The morphologic diagnosis in cases of neoplasia is the name of the neoplasm. Next to the morphologic diagnosis is the etiologic diagnosis, which should be restricted to a couple of words. It indicates the affected organ and information linking the tissue change to its cause. If a causal relationship can be established, then a cause should be also included with the preliminary or final diagnosis. It can be difficult to understand the making of a morphologic diagnosis, especially if you are trying it for the first time and are not used to the buzzwords that many pathologists use on a daily basis. It can be occasionally challenging to formulate a morphologic diagnosis even for experienced professionals. Pathology is all about repetition. Take a classic example of feline infectious peritonitis in a cat (Fig. 82).

Image Fig. 82. Fibrinous peritonitis due to feline infectious peritonitis virus infection in a cat. The abdomen is filled with fibrin and gelatinous contents (Image D.R. Rissi).

What would be a good way to describe that lesion and assign a morphologic and etiologic diagnosis to it? Start out with location: abdominal cavity or peritoneum. Tissue changes in this image consist of abdominal fluid and small white plaques on the liver and omentum, so it is better to address them separately. Here it is:

            Abdominal cavity: The abdominal cavity contains approximately 10 ml of dark yellow to brown, semi-translucent fluid admixed with fine, faintly yellow strands of fibrillar material that adhered to the intestinal serosa, omentum, and hepatic capsule. Diffusely covering the omentum and the hepatic capsule are multifocal to coalescing, pale white, roughly circular, slightly elevated, 1-3 mm in dimeter soft plaques.

            As you can see, not all the descriptor terms will apply to every single tissue change. In this case, shape and demarcation, size, and special features were not used when describing the abdominal fluid. What about an interpretation or morphologic diagnosis? The first thing is to choose a general pathologic process. You can use the chapters of a general pathology book as reference. This may be tricky because it will require some experience and knowledge of the clinical history. In this case we will go with inflammation. The fluid is serosanguineous (consistent with a modified transudate) and the faintly yellow strands of fibrillar material are typical of fibrin (exudate). Next is to choose the type of inflammation. In this case, fibrinous is the buzzword you will use. What about the age of the lesion? Is it acute, subacute, or chronic? The clinical evolution is helpful again, and you can use it when assessing this feature. If you have no access to a clinical history, keep in mind that fibrin is an acute inflammatory protein so this lesion is likely acute. Having that in mind, a good morphologic diagnosis would be:

            Morphologic diagnosis: Diffuse, acute, severe fibrinous peritonitis and hepatitis.

            As we discussed, this morphologic diagnosis is based on your gross anatomic description. It will be confirmed by histological examination or overturned by it (that is why it is preliminary). If you know feline medicine and the laws of nature, you know that cat + fibrin = feline infectious peritonitis (until proven otherwise, and that would be rare), so at this point you should feel pretty confident about your preliminary assessment of the case. Other cases will be different and you will have to modify or replace the preliminary diagnosis according to histology or other ancillary tests. Let us move on to the etiologic diagnosis and most likely cause.

            Etiologic diagnosis: Coronavirus peritonitis and hepatitis.
            Cause: Feline infectious peritonitis virus (mutated feline enteric coronavirus).

            Moving on to a different case (Fig. 83). This is a dog with multiple nodules throughout the liver.

Image Fig. 83. Hepatic cholangiocarcinoma in a dog. Multifocal to coalescing nodules with a central depression or umbilication due to necrosis efface the hepatic parenchyma (Image D.R. Rissi).

           
            Liver: The hepatic parenchyma is expanded and partially effaced by multifocal to coalescing, yellow, round to irregular, 2-50 mm in diameter, firm, slightly raised nodules that often have a central, red umbilication (depression). The remaining hepatic parenchyma is diffusely mottled yellow and red. 

            Morphologic diagnosis: Hepatic cholangiocarcinoma.

            How would you know this is a cholangiocarcinoma and not multiple granulomas? Because you know that a cholangiocarcinoma will look exactly like this virtually every single time you see one. Would anything else look like this? Sure, maybe it could be a metastatic carcinoma. In that case, replace your morphologic diagnosis accordingly and keep that in mind. Next time you see this lesion you should think of both and choose the most likely diagnosis, a hepatic cholangiocarcinoma. The etiologic diagnosis and the cause will be undetermined for most neoplasms. For others, such as cutaneous squamous cell carcinoma and bovine leukosis, chronic ultraviolet light exposure and retroviral infection can be listed as the most likely causes. Just like you follow a specific technique when performing a postmortem evaluation, you should also keep in mind all the main points you need to address to prepare a gross description. Conform to that system every time you do it and it will eventually become instinctive and flow naturally.

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