Pathology notes describing histological assessment of



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Table S3 Pathology notes describing histological assessment of Ciz1-/- mice from Supplemental Table 2.


Animal

Genotype

Organ

Pathology

1

-/-

Lungs

Prominent infiltrate of small to medium sized lymphocytes around bronchi, bronchioles and vessels, extending from the hilum to the periphery of the lung. The lung parenchyma, bronchi and vessels are normal and there is no dysplasia or malignancy of the respiratory epithelium.

Liver

The liver contains two large, nodular aggregates of small to medium sized lymphocytes adjacent to a large hepatic vein. Occasional, small parenchymal foci of lymphocytes and neutrophils are present. The background liver architecture, hepatocytes and bile ducts appear normal.

Spleen

The spleen shows expansion of the white pulp by small to medium sized lymphocytes.

Lymph nodes

Very large lymph nodes with effaced architecture and a nodular infiltrate of small to medium sized lymphocytes with extranodal extension.

Thymus

The thymus contains a nodular infiltrate of small to medium sized lymphocytes.

Reproductive tract

Normal uterus, ovary and oviduct.

Kidney

Aggregate of small to medium sized lymphocytes with scanty plasma cells in renal pelvis, focal lymphoid aggregates in parenchyma. Glomeruli, tubules, and vessels normal.

Pancreas

The pancreas contains a small lymphoid aggregate by a vessel and islet but is otherwise normal.

Salivary gland

Not identified

Bladder

Not identified

2

-/-

Lungs

The lungs contain a very prominent infiltrate of small to medium sized lymphocytes with larger blast-like cells in some areas. The infiltrate is present around bronchi, bronchioles and vessels, from hilum to lung periphery. Occasional granulomas are likely to be reactive. The lung parenchyma, bronchi and vessels are normal and there is no dysplasia or malignancy of the respiratory epithelium.

Liver

The liver contains numerous nodular infiltrates of small to medium sized lymphocytes with occasional larger blast-like cells. The infiltrates are mostly in periportal locations. There are also many foci of granulomatous inflammation at the periphery of the nodules and within the liver parenchyma which may be reactive. The background liver architecture, hepatocytes and bile ducts appear normal.

Spleen

The spleen shows expansion of the white pulp by small to medium sized lymphocytes.

Lymph nodes

One of the lymph nodes shows effaced architecture with an infiltrate of small to medium sized lymphocytes. Occasional larger lymphocytes. Two other nodes show a nodular infiltrate including small to medium sized lymphoid cells with larger blast-like cells. Occasional granulomas are present.

Thymus

Not included

Reproductive tract

Normal uterus

Kidney

Hilar and cortical aggregates of medium sized lymphocytes, most adjacent to vessels. Glomeruli, tubules, and vessels normal.

Pancreas

The pancreas contains a small lymphoid aggregate by a vessel but is otherwise normal.

Salivary gland

Not identified

Bladder

Not identified

3

-/-

Lungs

The lungs contain a moderate infiltrate of mostly small lymphocytes with occasional plasma cells around bronchi, bronchioles, vessels. The lung parenchyma, bronchi and vessels are normal and there is no dysplasia or malignancy of the respiratory epithelium.

Liver

The liver contains occasional focal aggregates of lymphocytes with pigmented macrophages and neutrophils in periportal, parenchymal and perivenular areas. Some of these foci are granulomatous. No large nodular infiltrates are present. A single tiny focus of extramedullary haematopoiesis is present. The background liver architecture, hepatocytes and bile ducts appear normal.

Spleen

The white pulp appears normal but the red pulp is expanded by extensive extramedullary haematopoiesis.

Lymph nodes

Normal

Thymus

Normal

Reproductive tract

Not identified

Kidney

The kidney contains a single tiny aggregate of lymphocytes and plasma cells by vessels. Glomeruli, tubules, and vessels normal.

Pancreas

The pancreas contains a periductal infiltrate of lymphocytes and plasma cells with a small focus of destruction of periductal acini, although the majority of the gland is normal.

Salivary gland

Normal parotid, submandibular and sublingual glands.

Bladder

The bladder contains a moderate number of mucosal and serosal aggregates of lymphocytes and plasma cells. The wall and epithelium are normal.

4

-/-

Lungs

The lungs contain an increased amount of lymphoid tissue around vessels and airways, consisting of small and medium sized lymphocytes with plasma cells. The lung parenchyma, bronchi and vessels are normal and there is no dysplasia or malignancy of the respiratory epithelium.

Liver

The liver contains large and sometimes conflent nodular infiltrates of small to medium sized, and occasionally large lymphoid cells with scanty plasma cells. Multiple small foci of neutrophils and eosinophils are present within the parenchyma. The background liver architecture, hepatocytes and bile ducts appear normal.

Spleen

The spleen contains a nodular infiltrate of small to medium sized lymphoid cells with some larger lymphoid cells.

Lymph nodes

An enlarged parotid lymph node shows effaced architecture and is infiltrated by small lymphoid cells.

Thymus

Normal

Reproductive tract

Normal uterus

Kidney

Normal

Pancreas

Normal

Salivary gland

Sublingual and parotid glands normal. Submandibular gland not present.

Bladder

There are 2 aggregates of lymphocytes and plasma cells in the mucosa. The wall and epithelium are normal.

5

-/-

Lungs

The lungs contain a slightly increased amount of lymphoid tissue around vessels and airways, consisting of small and medium sized lymphocytes with plasma cells. The lung parenchyma, bronchi and vessels are normal and there is no dysplasia or malignancy of the respiratory epithelium.

Liver

The liver contains a single nodular infiltrate of small lymphoid cells. Occasional small foci of inflammatory cells are present within the parenchyma. The background liver architecture, hepatocytes and bile ducts appear normal.

Spleen

Normal

Lymph nodes

Not identified

Thymus

Normal

Reproductive tract

Normal uterus. One ovary contains a multiloculated cyst lined by serous type epithelium.

Kidney

Normal renal parenchyma with dilated renal pelvis, possibly hydronephrosis.

Pancreas

Normal

Salivary gland

Normal submandibular gland. Sublingual and parotid not identified.

Bladder

There are 3 aggregates of lymphocytes and plasma cells in the mucosa. The wall and epithelium are normal.

8

-/-

Lungs

Prominent infiltrate of mostly small lymphocytes around vessels, less prominent around airways. In places medium sized and larger lymphoid cells, as seen in spleen, are also present. In some areas there are foamy macrophages in alveoli and an infiltrate of small to medium-sized lymphoid cells in the pleura. The bronchi and vessels are normal and there is no dysplasia or malignancy of the respiratory epithelium.

Liver

The liver contains small to large, nodular and confluent infiltrates of medium to large lymphoid cells in perivenular, periportal, and subcapsular areas with cells also filling sinusoids.

Spleen

The splenic architecture is effaced by an infiltrate of large lymphoid cells with frequent mitoses.

Lymph nodes

There are two or more lymph nodes with an infiltrate of mixed small to medium sized lymphoid cells. Two parotid nodes with a similar infiltrate also including plasma cells are present. There are several very large nodes containing an infiltrate of small to medium sized lymphoid cells with extranodal extension.

Thymus

Not identified

Reproductive tract

Not identified

Kidney

Normal glomeruli and tubules. There is a patchy interstitial infiltrate of medium to large lymphoid cells in the cortex and around vessels. The perinephric fat contains an infiltrate of small to medium sized lymphoid cells.

Pancreas

Normal

Salivary gland

There are occasional small lymphoid aggregates in the submandibular gland. Normal parotid and sublingual glands.

Bladder

Not identified



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