**Core Concept**
Cryptococcosis is a fungal infection caused by Cryptococcus neoformans, primarily affecting the lungs and central nervous system. The investigation of choice for diagnosing cryptococcosis involves identifying the fungal capsular polysaccharide, known as cryptococcal antigen (CrAg), in the patient's cerebrospinal fluid (CSF) or serum.

**Why the Correct Answer is Right**
The correct investigation of choice for cryptococcosis is the detection of cryptococcal antigen (CrAg) in the CSF or serum. This is done using latex agglutination or enzyme immunoassay (EIA) tests. These tests detect the presence of the capsular polysaccharide, which is a specific antigen produced by Cryptococcus neoformans. The detection of CrAg in the CSF is particularly useful for diagnosing cryptococcal meningitis, a common manifestation of cryptococcosis in immunocompromised individuals.

**Why Each Wrong Option is Incorrect**
**Option A:** Imaging studies such as CT or MRI scans may be used to support the diagnosis of cryptococcosis, but they are not the investigation of choice. They can help identify the location and extent of the infection but cannot confirm the diagnosis.
**Option B:** Blood cultures may be positive in cases of cryptococcosis, but they are not the most sensitive or specific method for diagnosing the infection. The detection of CrAg in the CSF or serum is more reliable.
**Option C:** Histopathological examination of tissue samples may be used to diagnose cryptococcosis, but it is an invasive procedure and not the preferred method for initial diagnosis.

**Clinical Pearl / High-Yield Fact**
Cryptococcal antigen (CrAg) testing is a crucial diagnostic tool for cryptococcosis, particularly in immunocompromised patients. A positive CrAg test in the CSF or serum can help guide treatment and improve outcomes.

**Correct Answer:** C.