INI-CET 2026 - Pathology Practice Questions

Q: On histopathological examination of the gastro-esophageal junction, the following image is observed. What is the probable diagnosis?

Barrett's esophagus. ***Barrett's esophagus*** - Characterized by the presence of **intestinal metaplasia** (columnar epithelium with **goblet cells**) replacing the normal stratified squamous epithelium of the distal esophagus. - Clinically, this is a distinct complication of chronic **gastroesophageal reflux disease (GERD)** and is a recognized precursor lesion for esophageal adenocarcinoma. *Low grade dysplasia* - Refers to a higher level of architectural and cytologic atypia than simple metaplasia but does not show the invasive features of carcinoma. - While Barrett's esophagus can progress to dysplasia, the defining histologic feature of Barrett's itself is the presence of **intestinal metaplasia**. *Squamous cell carcinoma* - Typically originates from the **stratified squamous epithelium** lining the mid-esophagus rather than the gastro-esophageal junction. - Histopathologically presents with **keratin pearls** and intercellular bridges, which are distinct from the glandular metaplasia seen in Barrett's. *Adenocarcinoma* - This malignancy arises directly from glandular tissue, often within a background of Barrett's esophagus. - Unlike Barrett's which is a metaplastic change, adenocarcinoma is defined by **invasive glandular structures** infiltrating into the submucosa or deeper layers.

Q: A pathologist receives a formalin-fixed paraffin-embedded (FFPE) tissue section. Which technique is most appropriate to identify and localize specific proteins within this section in situ?

Immunohistochemistry (IHC). ***Immunohistochemistry (IHC)*** - This technique utilizes **specific antibodies** to detect and visualize target proteins directly within tissue sections, maintaining the **tissue architecture**. - It is the gold standard for **in situ protein localization** in formalin-fixed paraffin-embedded (FFPE) tissue, allowing pathologists to correlate protein expression with specific histological features. *Fluorescence in situ hybridisation (FISH)* - This molecular technique is specifically designed to detect **DNA or RNA sequences** rather than proteins within a cell. - It relies on **fluorescent probes** that bind to specific chromosomal or genetic targets, not the localization of proteins. *Flow cytometry* - While it can analyze protein expression, this technique requires the tissue to be dissociated into a **single-cell suspension**. - Because it destroys the **tissue architecture** and spatial relationships between cells, it is not used to localize proteins within an intact tissue section. *Western blot* - This technique is used to measure the **size and quantity** of a specific protein within a sample. - It requires total protein extraction from the sample, which destroys the **morphology and spatial distribution** of proteins, making it unsuitable for in situ localization.

Q: A patient from North-East India presents with pulmonary cavitary lesions and hepatic nodules. Sputum AFB smear is negative. Biopsy shows caseating granulomas with Langhans-type giant cells and raised ESR. What is the most probable diagnosis?

Tuberculosis. ***Tuberculosis*** - Pulmonary **cavitary lesions** combined with **hepatic granulomas** in an endemic region like North-East India are highly characteristic of **disseminated tuberculosis**. - The biopsy finding of **caseating granulomas** with **Langhans-type giant cells** is the gold-standard histological hallmark of **Mycobacterium tuberculosis** infection. *Toxoplasmosis* - Typically presents as an opportunistic infection in **immunocompromised hosts** (e.g., HIV), manifesting as **ring-enhancing brain lesions** rather than pulmonary cavities. - Histologically shows **cysts** containing bradyzoites or free tachyzoites, not **caseating granulomas**. *Histoplasmosis* - Though it can mimic tuberculosis with pulmonary nodules and cavitary disease, it is classically associated with **yeast forms** within macrophages. - Biopsy would reveal **non-caseating** or poorly formed granulomas and classic **narrow-based budding yeasts**, which are distinct from the caseation seen here. *Sarcoidosis* - Classically presents with **bilateral hilar lymphadenopathy** and pulmonary infiltrates rather than destructive **cavitary lesions**. - Histology demonstrates **non-caseating granulomas** (naked granulomas), whereas the presence of **caseation** strongly points toward an infectious etiology like TB.

Q: An 8-year-old boy presents with freckling in the armpits, soft skin tumors over the back, and learning difficulties. His father has similar skin lesions. The images show findings under slit lamp. What is the most likely diagnosis?

Neurofibromatosis type 1 (NF1). ***Neurofibromatosis type 1 (NF1)*** - Characterized by diagnostic criteria including **axillary freckling (Crowe sign)** and multiple **neurofibromas**, which are soft, flesh-colored peripheral nerve sheath tumors. - The slit lamp examination in individuals with NF1 typically reveals **Lisch nodules** (iris hamartomas), which are pathognomonic for this condition. *Neurofibromatosis type 2 (NF2)* - Manifests primarily with **bilateral vestibular schwannomas**, leading to hearing loss and tinnitus, rather than the cutaneous features described. - It is less commonly associated with the specific combination of axillary freckling and neurofibromas seen in type 1. *Tuberous sclerosis complex* - Presents with **angiofibromas**, ash-leaf spots (hypopigmented macules), and **shagreen patches** instead of neurofibromas. - Commonly associated with neurological manifestations like **seizures** and intellectual disability rather than the classic NF1 signs. *Sturge-Weber syndrome* - Identified by a **port-wine stain (nevus flammeus)** in the distribution of the ophthalmic branch of the trigeminal nerve. - Associated with **leptomeningeal angiomas**, which often cause seizures and glaucoma, distinct from the neurocutaneous tumors of NF1.

Q: What is the primary molecular mechanism by which UV light induces carcinogenesis?

Thymine dimers. ***Thymine dimers*** - UV radiation, particularly **UVB**, causes structural damage to **DNA** by inducing the formation of **pyrimidine dimers** (specifically cyclobutane pyrimidine dimers involving thymine residues) between adjacent bases. - If these lesions are not effectively repaired by the **nucleotide excision repair (NER)** pathway, they lead to **mutations** (commonly C to T transitions) in critical genes like **TP53** during DNA replication, driving carcinogenesis. *Inhibition of TP53* - While UV damage often leads to mutations in the **TP53 gene**, this is a downstream consequence of DNA damage, not the primary molecular mechanism of UV-induced injury itself. - **TP53** is typically inactivated via **mutations** caused by failed repair of DNA photoproducts, rather than direct inhibition of the protein by UV light. *Activation of NF-kappa beta signaling pathway* - The **NF-kappaB pathway** is primarily involved in **inflammatory and immune responses** rather than being the direct mechanism of DNA damage-induced carcinogenesis. - While UV exposure does activate inflammatory pathways, this is a secondary response to tissue stress and not the foundational cause of **mutagenesis** and cancer initiation. *Upregulation of cyclin proteins* - Uncontrolled cell cycle progression due to **cyclin** dysregulation is a hallmark of cancer, but it is a result of accumulated **genetic mutations**. - This represents a cellular outcome of cancer development rather than the direct photochemical event initiated by UV radiation interacting with genomic DNA.

Q: On histopathological examination of liver from a chronic alcoholic, the following image is observed. Which special stain is the best choice to confirm the diagnosis?

Masson Trichrome. ***Masson Trichrome*** - This stain is the gold standard for visualizing **fibrosis** and connective tissue, which appear blue or green against a red background of hepatocytes. - In a patient with chronic alcoholism, it effectively highlights the **pericellular fibrosis** and **bridging fibrosis** characteristic of cirrhotic liver progression. *Gomori Methenamine Silver (GMS)* - Primarily utilized to identify **fungal organisms**, such as *Pneumocystis jirovecii* or *Candida* species. - It has no role in assessing hepatic fibrosis or the structural architecture of the liver in chronic alcohol abuse. *Periodic Acid Schiff (PAS)* - Frequently used to detect **glycogen** or **mucins** in tissues; it is particularly useful for identifying diastase-resistant globules in **Alpha-1 Antitrypsin Deficiency**. - While it can stain some basement membranes, it is not the standard choice for quantifying or visualizing fibrous septa in cirrhosis. *Gram stain* - Specifically designed to classify bacteria into **Gram-positive** and **Gram-negative** groups based on their cell wall composition. - It provides no utility in evaluating chronic liver parenchymal damage or the extent of fibrotic deposition in alcoholic liver disease.

Question 1

On histopathological examination of the gastro-esophageal junction, the following image is
observed. What is the probable diagnosis?

Accepted Answer

Barrett's esophagus

Answer

Low grade dysplasia

Answer

Squamous cell carcinoma

Answer

Adenocarcinoma

Question 2

A pathologist receives a formalin-fixed paraffin-embedded (FFPE) tissue section. Which
technique is most appropriate to identify and localize specific proteins within this section in situ?

Accepted Answer

Immunohistochemistry (IHC)

Answer

Flow cytometry

Answer

Western blot

Answer

Fluorescence in situ hybridisation (FISH)

Question 3

A patient from North-East India presents with pulmonary cavitary lesions and hepatic nodules.
Sputum AFB smear is negative. Biopsy shows caseating granulomas with Langhans-type giant
cells and raised ESR. What is the most probable diagnosis?

Accepted Answer

Tuberculosis

Answer

Toxoplasmosis

Answer

Histoplasmosis

Answer

Sarcoidosis

Question 4

An 8-year-old boy presents with freckling in the armpits, soft skin tumors over the back, and
learning difficulties. His father has similar skin lesions. The images show findings under slit lamp.
What is the most likely diagnosis?

Accepted Answer

Neurofibromatosis type 1 (NF1)

Answer

Neurofibromatosis type 2 (NF2)

Answer

Tuberous sclerosis complex

Answer

Sturge-Weber syndrome

Question 5

What is the primary molecular mechanism by which UV light induces carcinogenesis?

Accepted Answer

Thymine dimers

Answer

Inhibition of TP53

Answer

Activation of NF-kappa beta signaling pathway

Answer

Upregulation of cyclin proteins

Question 6

On histopathological examination of liver from a chronic alcoholic, the following image is
observed. Which special stain is the best choice to confirm the
diagnosis?

Accepted Answer

Masson Trichrome

Answer

Gomori Methenamine Silver (GMS)

Answer

Periodic Acid Schiff (PAS)

Answer

Gram stain

INI-CET 2026 — Pathology