Kidney and Bladder Neoplasia Pathology Study Guide

Kidney and Bladder Neoplasia Pathology Video

Kidney and bladder neoplasia includes:

Angiomyolipoma
Renal cell carcinoma
Wilms tumor
Urothelial carcinoma
Squamous cell carcinoma of the bladder
Adenocarcinoma of the bladder

Angiomyolipoma

Angiomyolipoma is a disorder where benign kidney tumors develop.

Angiomyolipoma a tumor made up of blood vessels, smooth muscle, and adipose tissue.

Tuberous sclerosis is associated with angiomyolipoma.

Angiomyolipoma. Not altered. CC BY-SA 3.0
Angiomyolipoma. Seen as a hyperechoic mass in the upper pole of an adult kidney on renal ultrasonography. Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - Not altered. CC BY 4.0
Angiomyolipoma. Renal ultrasonography of a person with tuberous sclerosis and multiple angiomyolipomas in the kidney: Measurement of kidney length on the US image is illustrated by '+' and a dashed line. Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - Not altered. CC BY 4.0
Angiomyolipoma. Myoid cells with clear cytoplasm spinning off of large vessels in a background of mature fat, the classic microscopic features of angiomyolipoma Jerad M Gardner, MD. Not altered. CC BY-SA 3.0
Hematoxylin and eosin staining (×200) showed that the tumors were composed of mature adipose fat cells, bundles of smooth muscle, thick-walled blood vessels with peripherally compressed adrenal cortical tissue suggestive of angiomyolipoma of adrenal (A). Tumor cells exhibited diffuse immunoreactivity for human melanoma black-45 (B), Melan-A (C), and smooth muscle actin (D) confirmed the diagnosis of adrenal angiomyolipoma. High 18F-Fluorodeoxyglucose Uptake in Adrenal Angiomyolipoma: Case Report and Review of Literature: Li W, Pang H, Cao Y, Guan L, Chen J - Medicine (2015). Not altered. CC.

Renal Cell Carcinoma (RCC)

Renal cell carcinoma (RCC) is a malignant cancer cells are located in the lining of kidney tubules, which are incredibly tiny tubes. This condition is known as renal cell carcinoma.

Symptoms of renal cell carcinoma include:

Hematuria (most common)
Palpable mass
Flank pain
Fever
Weight loss
Paraneoplastic issues

Rarely, renal cell carcinoma may present with a left-sided varicocele.

The left spermatic vein cannot drain properly due to cancer in the left renal vein, which causes a varicocele.

Right-sided varicocele is not seen because the right spermatic vein empties straight into the inferior vena cava (IVC).

When examined under a microscope, the most common variant of renal cell carcinoma shows clear cytoplasm or a clear cell type.

Loss of the tumor suppressor gene VHL causes an increase in the growth-promoting hormone IGF-1 and the transcription factor HIF, which in turn causes an increase in the growth hormones VEGF and PDGF.

Renal cell carcinomas (RCCs) may be hereditary or sporadic.

Risk factors for sporadic renal cell carcinoma (RCC) includes:

Male
Age of 60 or older
Smoking

Hereditary renal cell carcinomas (RCCs) typically develop in younger adults and are bilateral.

The autosomal dominant illness known as von Hippel-Lindau disease increases the risk of renal cell carcinoma (RCC) and cerebellar hemangioblastoma by inactivating the VHL gene.

Renal Cell Carcinoma. Histopathologic types of kidney tumor, with relative incidences and prognoses, including renal cell carcinoma and its subtypes Mikael Häggström, M.D. Not altered. CC0
Renal Cell Carcinoma. Left renal tumor with inferior vena cava thrombus into the right atrium Medkatz - Not altered. CC BY-SA 4.0
Renal cell carcinoma. Ed Uthman, MD. Not altered. Public Domain
Renal Cell Carcinoma. Generally the cells have a clear cytoplasm, are surrounded by a distinct cell membrane and contain round and uniform nuclei. KGH Not altered. CC BY-SA 3.0
Renal Cell Carcinoma. Type 1 PRCC consist of papillae covered with a single or double layer of small cuboid cells with scanty cytoplasm and Type 2 PRCC consist of papillae covered by large eosinophilic cells arranged in an irregular or pseudostratified manner. Nephron. Not altered. CC BY-SA 3.0
Renal Cell Carcinoma. Ed Uthman, MD. Not altered. Public domain
Renal Cell Carcinoma. Micrograph showing a large artery with foreign material - result of an embolization procedure prior to a nephrectomy for renal cell carcinoma. The renal cell carcinoma is not shown on the image. Kidney - cortex: multiple glomeruli and tubules are seen. H&E stain. Low power. Nephron. Not altered. CC BY-SA 3.0
Kidney and Bladder Neoplasia Pathology. High magnification micrograph of a clear cell renal cell carcinoma. H&E stain. Features: Cells with clear cytoplasm, typically arranged in nests. Nuclear atypia is common. The case seen in the image has Fuhrman grade 2/4; the nuclear atypia is moderate and nucleoli could not be seen at 100 X. Related images High mag. (cropped) High mag. Intermed. mag. Nephron. Not altered. CC BY-SA 3.0
Chromophobe Renal Cell Carcinoma. Ed Uthman. Not altered. CC BY 2.0

Wilms Tumor

Wilms tumor is a malignant kidney tumor composed of primitive glomeruli, tubules, and stromal cells blastema which is an immature kidney mesenchyme.

The average age of a child who develops a Wilms tumor is 3-years-old.

Symptoms of Wilms tumor include:

Large mass
Unilateral flank mass
Hematuria
Hypertension brought on by renin secretion

Wilms tumor is associated with WT1 mutation, especially in syndromic cases.

WAGR syndrome is the disease called for its features, which include:

Wilms tumor
Aniridia
Genitourinary abnormalities
Intellectual impairment

Beckwith-Wiedemann syndrome is another disease associated with Wilms tumor, and includes:

Wilms tumor
Neonatal hypoglycemia
Muscular hemihypertrophy
Organomegaly

Wilms Tumor. Cut section showing two halves of a nephroblastoma specimen. Note the prominent septa subdividing the sectioned surface and the protrusion of tumor into the renal pelvis, resembling botryoid rhabdomyosarcoma. The Armed Forces Institute of Pathology. Not altered. Public Domain
Wilm’s Tumor (Nephroblastoma). Ed Uthman. Not altered. CC BY 2.0
Wilms Tumor. Low magnification micrograph showing the characteristic triphasic pattern consisting of tubules, solid sheets of small round cells, and stroma. H&E stain. Nephron - Not altered. CC BY-SA 3.0
Wilms Tumor. Histopathology of Wilms' tumor, showing its three elements: blastema, mesenchyme (stroma) and epithelium. H&E stain. Mikael Häggström, M.D. Not altered. CC0
WT-1 expression in melanoma and Spitz's nevi. Paraffin-embedded tissue sections from patients with melanocytic lesions were immunostained for WT-1 protein. Circles identify morphologically similar malignant and benign melanocytes with distinct WT-1 immunoreactivities. Note that all or nearly all the tumor cells of in situ and spreading melanomas (a-d) were strongly and uniformly positive for WT-1. Similar WT-1 immunostaining was also seen in all or nearly tumor cells in both the junctional and dermal components of Spitz's nevi (e-h). a, c, e, and g: 100X. b, d, f, and h: a higher magnification (300X) of a, c, e, and g, respectively. WT-1 expression in a spectrum of melanocytic lesions: Implication for differential diagnosis. Chung LS, Man YG, Lupton GP - Journal of Cancer (2010). Not Altered. CC.

Urothelial Carcinoma

Urothelial carcinoma is also known as transitional cell carcinoma.

The epithelial lining of the renal pelvis, ureter, bladder, or urethra is the source of this malignant tumor.

Urothelial carcinoma is the most typical type of bladder cancer.

Risk factors for urothelial carcinoma include:

Cigarette smoke (major risk factor)
Naphthylamine
Azo dyes
Cyclophosphamide
Phenacetin

The typical presentation of urothelial carcinoma is painless hematuria in an adult.

Urothelial carcinoma arises via two distinct pathways:

Flat
Papillary

Flat urothelial carcinoma is characterized by the invasion of a high-grade flat tumor and is associated with p53 early mutations.

Papillary urothelial carcinoma initially appears as a low-grade papillary tumor, advances to a high-grade papillary tumor, then invades, and is not linked to early p53 mutations.

A field defect is when a tumor recurs and is frequently multifocal in nature.

Urothelial Carcinoma. Bladder diverticula containing stones. Also note that the bladder wall is thickened due to possible transitional cell carcinoma. James Heilman, MD - Not altered. CC BY-SA 4.0
Papillary Urothelial Carcinoma. Bladder urothelial carcinoma pT1 Not altered. CC BY-SA 3.0
Small Cell Carcinoma of the Bladder. Pathology of small cell carcinoma of the bladder. A. Hematoxylin and eosin (H and E) staining of the biopsy specimen, low-power view: Urothelial mucosa unfiltered by poorly differentiated carcinomatous proliferation comprised sheets of monomorphic cells. B. Hematoxylin and eosin (H and E) staining of the biopsy specimen, high-power view (×20): Proliferation comprised small cells with hyperchromatic nuclei infiltrating the muscle. C. Hematoxylin and eosin (H and E) staining: High-power view (×40) of a transurethral resection of small cell carcinoma, showing typical scant cytoplasm, increased mitotic index, spindling, and prominent nuclear moulding. D. Immunostaining: NSE-antibody-positive bladder tumor cells. A rare bladder cancer--small cell carcinoma: review and update. Ismaili N - Orphanet journal of rare diseases (2011). Not altered. CC.
Urothelial Carcinoma. Histopathology of urothelial carcinoma of the urinary bladder, showing a nested pattern of invasion. Transurethral biopsy. Hematoxylin and eosin. No machine-readable author provided. KGH assumed (based on copyright claims). - Not altered. CC BY-SA 3.0
Urothelial Carcinoma. Papillary transitional cell carcinoma, low grade CoRus13 - Not altered. CC0
Urothelial Carcinoma. Histopathology of urothelial carcinoma of the urinary bladder. No machine-readable author provided. KGH assumed (based on copyright claims). -Not altered. CC BY-SA 3.0
Urothelial Carcinoma. Histopathology of urothelial carcinoma of the urinary bladder. No machine-readable author provided. KGH assumed (based on copyright claims). - Not altered. CC BY-SA 3.0
Urothelial Carcinoma. Micrograph of urothelial cell carcinoma of the prostatic urethra on a prostate biopsy. H&E stain. Normal prostatic glands (with two cell layers) are seen on the far right of the image. At the top and centre of the image are nests of urothelial cell carcinoma, characterized by prominent nucleoli and marked variation of nuclear size. Slightly left-of-centre, it is possible to discern two cell populations in a prostatic gland: non-malignant prostatic epithelium with small darker stained nuclei, and neoplastic urothelium, with larger nuclei. Nephron . Not altered. CC BY-SA 3.0
Histologic grading of urothelial tumors: (A) The 2004 WHO classification Papillary urothelial neoplasm of low malignant potential (PUNLMP); (B) the 1973 WHO classification grade 3 urothelial carcinoma. The 1973 WHO Classification is more suitable than the 2004 WHO Classification for predicting prognosis in non-muscle-invasive bladder cancer. Chen Z, Ding W, Xu K, Tan J, Sun C, Gou Y, Tong S, Xia G, Fang Z, Ding Q - PloS one (2012). Not altered. CC.
Histopathology of murine nitrosamine-induced bladder carcinoma mimics progression of human urothelial carcinoma in situ(a,b) Histopathological analysis (H&E staining) of early (a) and late (b) stages of BBN-induced bladder carcinogenesis (see also Supplementary Table 1). Lower panels show magnified views of the boxed regions in upper panels. Note the appearance, beginning at 3 months of BBN exposure, of histologic abnormalities, including nuclear atypia, crowding, and architectural disarray histologically identical to human carcinoma in situ (CIS), and leading to invasive carcinoma by six months of BBN exposure. L, bladder lumen. Scale bars, 50μm. Repeated experimental results are shown in Supplementary Table 1.Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma. Shin K, Lim A, Odegaard JI, Honeycutt JD, Kawano S, Hsieh MH, Beachy PA - Nature cell biology (2014). Not Altered. CC.
A: Histological examination showed high-grade urothelial carcinoma with squamous differentiation (HE ×400). B: Immunohistochemical stain showed the tumor cells were positive for G-CSF, stained brown (anti-G-CSF antibody staining ×400). Granulocyte-Colony Stimulating Factor Producing Infiltrating Urothelial Carcinoma of the Left Renal Pelvis: A Case Report: Urology Case Reports. Not altered. CC.
Urothelial Carcinomas. Representative photography of 5-MeC and DNMT1 immunohistochemistry. The 5-MeC photography in A–E; The DNMT1 photos in F–J. (A,F) High-grade urothelial carcinoma showing high levels of both 5-MeC and DNMT1; (B,G) Low-grade urothelial carcinoma showing high levels of both 5-MeC and DNMT1; (C,H) High-grade urothelial carcinoma with glandular differentiation, showing high 5-MeC but low DNMT1 levels. (D,I) High-grade urothelial carcinoma with squamous differentiation, showing low levels of both 5-MeC and DNMT1; (E,J) High-grade urothelial carcinoma showing low levels of both 5-MeC and DNMT1. Bar = 200 µm. Reduced 5-methylcytosine level as a potential progression predictor in patients with T1 or non-invasive urothelial carcinoma. Chung CJ, Chang CH, Chuu CP, Yang CR, Chang YH, Huang CP, Chen WC, Chung MC, Chang H - International journal of molecular sciences (2014). Not Altered. CC.
High Grade Papillary Urothelial Carcinoma. Lamina propria invasion in a high-grade papillary urothelial carcinoma: T1m/ROL1 substaging (T1 < 0.5 mm). Usefulness of pT1 substaging in papillary urothelial bladder carcinoma. Patriarca C, Hurle R, Moschini M, Freschi M, Colombo P, Colecchia M, Ferrari L, Guazzoni G, Conti A, Conti G, Lucianò R, Magnani T, Colombo R - Diagnostic pathology (2016). Not altered. CC.
High-Grade Papillary Urothelial Carcinoma. Multiple foci of lamina propria invasion in a high-grade papillary urothelial carcinoma: T1e/ROL2 substaging (multifocality of invasion cumulatively amounting to more than 1 mm, i.e. > 200x field). Usefulness of pT1 substaging in papillary urothelial bladder carcinoma. Patriarca C, Hurle R, Moschini M, Freschi M, Colombo P, Colecchia M, Ferrari L, Guazzoni G, Conti A, Conti G, Lucianò R, Magnani T, Colombo R - Diagnostic pathology (2016). Not altered. CC.

Squamous Cell Carcinoma of the Bladder

The second most prevalent type of bladder cancer is squamous cell carcinoma (SCC) of the bladder.

Squamous cell carcinoma (SCC) of the bladder is characterized by abnormal, accelerated squamous cell proliferation.

The normal bladder surface is not coated with squamous epithelium, hence this cancer develops against a backdrop of squamous metaplasia.

Symptoms of squamous cell carcinoma (SCC) of the bladder include:

Chronic cystitis in older women
Infection with Schistosoma haematobium in Egyptian males
Persistent nephrolithiasis

Squamous Cell Carcinoma of the Bladder. Main histopathology features of squamous-cell carcinoma Mikael Häggström. Not altered. CC0

Adenocarcinoma of the Bladder

Adenocarcinoma of the bladder is a type of bladder cancer due to malignant glandular cells.

Adenocarcinoma of the bladder may arise from:

Cystitis glandularis
Exstrophy

Cystitis glandularis is associated with a urachal remnant and causes adenocarcinoma of the bladder that develops near the dome of the bladder.

Exstrophy is a congenital failure to form the caudal portion of the anterior abdominal and bladder walls.

Adenocarcinoma of the Bladder. Transitional cell carcinoma of the bladder. The white in the bladder is contrast. James Heilman, MD. Not altered. CC BY-SA 4.0
Adenocarcinoma of the Bladder. Badder wall thickening due to cancer James Heilman, MD. Not altered. CC BY-SA 4.0
Adenocarcinoma of the Bladder. a: Primary bladder adenocarcinoma, enteric type. Moderately differentiated malignant glands are seen with dirty luminal necrosis. Elongated, enlarged and hyperchromatic nuclei with prominent stratification line the malignant glands. (Hematoxylin & eosin, x100). b: Primary bladder adenocarcinoma, mucinous type. Scattered small groups of tumor cells with intracytoplasmic mucin are seen in a background of abundant mucinous material (Hematoxylin & eosin, x200). c: Primary bladder adenocarcinoma, signet ring cell type: Tumor comprised of diffuse sheets of signet ring cells infiltrating the bladder wall (Hematoxylin & eosin, x200). d: Cystitis cystica involving the surface urothelium with underlying invasive primary bladder adenocarcinoma (Hematoxylin & eosin, x100). e: Extensive cystitis glandularis, intestinal type seen adjacent to a focus of invasive primary bladder adenocarcinoma (not seen in this image) (Hematoxylin & eosin, x40). f: Metastatic colorectal adenocarcinoma. Moderately differentiated, infiltrating malignant glands with morphological features similar to primary bladder adenocarcinoma see in a (Hematoxylin & eosin, x100). Primary bladder adenocarcinoma versus metastatic colorectal adenocarcinoma: a persisting diagnostic challenge. Roy S, Smith MA, Cieply KM, Acquafondata MB, Parwani AV - Diagnostic pathology (2012). Not altered. CC.