Clinical Pathology of Urological Tumours - 1st Edition

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Contents

List of contributors vii Part 8 Clinical significance of treatment

Preface ix effects 117
Part 9 Prognosis of prostate cancer 121
Section 1 Renal tumors 1 Part 10 Inherited susceptibility, somatic gene
defects, and androgen receptors 131
Part 1 Epidemiology, etiology, and clinical Part 11 Rare forms of tumors 134
history 2 Part 12 Non-epithelial tumor-like conditions
Part 2 Pathology 3 and tumors of the prostate stroma 139
Part 3 Tumor genetics 19 Part 13 Miscellaneous, secondary, and
Part 4 Differential diagnosis and use of lymphoid tumors of the prostate 142
ancillary methods for diagnosis 23 Part 14 Appendices 143
Part 5 Principles of staging and grading 25
Part 6 Pediatric tumors 35 Section 5 Tumors of the seminal vesicles 157

Section 2 Adrenal glands 43 Section 6 Tumors of the testis and

paratesticular structures 161
Section 3 Pathology of tumors of the Introduction 162
urinary bladder 57 Part 1 Germ cell tumors 164
Section 4 Prostate cancer origins, diagnosis, Part 2 Intratubular germ cell neoplasia,
and prognosis in clinical practice 91 unclassified (IGCNU) 168
Part 3 Seminomas 170
Introduction 92 Part 4 Non seminomatous and mixed
Part 1 Proposed preneoplastic lesions and germ cell tumors 176
conditions 93 Part 5 Tumors of sex cord/gonadal stroma 189
Part 2 Atypical small acinar proliferation Part 6 Miscellaneous tumors of the testis 198
suspicious for but not diagnostic
of malignancy 97 Section 7 Squamous cell carcinoma
Part 3 Clinical features of prostate cancer 100 of the penis 215
Part 4 Methods of tissue diagnosis Section 8 Handling of surgical specimens 233
of prostate cancer 101
Part 5 Diagnostic criteria for prostate cancer 102 Section 9 Pathology of tumors of the renal
Part 6 Histologic classification of carcinoma pelvis and ureter, and the
of the prostate 106 urethra 235
Part 7 Current clinical practice of Gleason
grading of prostate cancer 111 Index 243
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Contributors

Matteo Brunelli MD Roberta Mazzucchelli MD PhD

Assistant Professor Institute of Pathological Anatomy and Histopathology
Department of Pathology Polytechnic University of the Marche Region
University of Verona Ancona
Italy Italy

Liang Cheng MD Gregor Mikuz MD FRCPath

Departments of Pathology and Laboratory Medicine Professor of Pathology
Indiana University School of Medicine Medical University Innsbruck
Indianapolis Innsbruck
USA Austria
Maurizio Colecchia MD Rodolfo Montironi MD FRCPath
Dipartimento di Patologia Institute of Pathological Anatomy and Histopathology
Instituto Nazionale per lo Studio e la Cura dei Tumori Polytechnic University of the Marche Region
Milano Ancona
Italy Italy
Antonio L Cubilla MD Maurizio Pea MD
Professor of Pathology Consultant Pathologist
Facultad de Ciencias Medicas Department of Pathology
University Nacional de Asunción University of Verona
Director Instituto de Patología e Investigacion Italy
Asunción
Paraguay Marina Scarpelli MD
Section of Pathological Anatomy and Histopathology
Vincenzo Ficarro MD Polytechnic University of the Marche Region
Associate Professor Ancona
Department of Urology Italy
University of Padua
Italy Regina Tardanico MD
Consultant Pathologist
Stefano Gobbo MD Department of Pathology
Fellow University of Brescia
Department of Pathology Italy
University of Verona
Italy Elsa F Velazquez MD
Assistant Professor of Pathology
Antonio Lopez-Beltran MD PhD Harvard Medical School
Department of Pathology Associate Pathologist
Reina Sofia University Hospital and Cordoba University Brigham & Women’s Hospital
Medical School Boston, MA
Cordoba USA
Spain
Alfredo Vidal-Jimenez
Guido Martignoni MD Unit of Anatomic Pathology
Associate Professor Cordoba University Medical School and
Department of Pathology Reina Sofia University Hospital
University of Verona Cordoba
Italy Spain
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Preface

Since 1890, when in Paris urology became a separate course of study overview of the morphology of the tumors of the genitourinary
from general surgery, this speciality has developed into a field of system. The international classifications, grading, and staging pro-
medicine in which science, technical developments, diagnostic pro- cedures which are included, as well as the rules for sampling and
cedures, and invasive as well as non-invasive therapeutic measures handling of the biopsy and surgical specimens, should permit a
have reached their highest levels. Urologic admissions and surgical better understanding of the morphologic assessment of the tumor
procedures are among the most frequently performed interventions diseases. The uses of modern morphologic techniques for differential
in current hospital care. In 1992, a century later, pathologists dealing diagnostic purposes are presented in order to show clinicians what
with urologic problems founded an international society of this sub- the current possibilities and limits of a pathologic diagnosis are.
specialization. Long before, however, outstanding pathologists on both A book written by many authors has both weaknesses and
sides of the Atlantic devoted their lives to the study of urologic disease, strengths. We take into account that the single chapters differ in
mainly tumors arising in the genitourinary system. Pathologists and style, which may disturb some readers. Yet we regard this also as a
urologists have learned in recent decades to discuss very open- strength because the very personal approach of the authors reflects
mindedly the common issues and have achieved in many institutions their longstanding diagnostic and scientific careers, which have
an exemplary degree of reciprocal understanding. The cooperation undergone much scrutiny and testing at international congresses
is not limited to daily diagnostics but rather, extends to common and classification committees, and in scientific papers and books.
scientific approaches and work. Moreover, tumors of the genitourinary system cannot be com-
The efforts of the uropathologists led to new generally accepted pared with those of other systems. Gastrointestinal tract tumors,
WHO classifications of urologic tumors, which are indispensable for for example, have a very similar morphology and prognostic
therapy planning and for the comparison of the results among assessment observes the same rules for all single segments. Prostate
different institutions. Many of the new morphologic tumor classifi- and testis tumors do not have anything in common except the
cations are already based on knowledge achieved through new gender of the patients. The bare history of the grading of bladder
methods, which allow the pathologists to analyze chromosomes and cancer, which has changed three times in the last 10 years, would
genes as well as their aberrations and mutations even in the ‘dead’ deserve its own chapter. Kidney tumors are the first example of a
cells of paraffin-embedded tissue. Alterations of the tumor cell classification based on the karyotype of the tumor. Tumors of the
genome are entering into daily pathologic routines and will in the adrenals are still a diagnostic problem because they are so rare. Last
near future permit a more individual therapeutic approach. Never- but not least, the penis carcinoma, which is practically unknown in
theless, at present surgery is still the first and most important proce- Europe and the US, requires an expert who confronts this problem
dure in the basic therapy of urologic tumors and biopsy the most daily.
important diagnostic approach (1 million prostate biopsies world- On behalf of all the authors, I venture to extend a debt of grati-
wide!). Even for chemotherapy treatment, morphology is used for tude to all those anonymous colleagues and friends who with their
the choice of drugs and for the assessment of their effectiveness. comments and questions have enlarged and enriched our experience.
This book is not intended as a ‘workbench’ book or an atlas for I also thank all our partners who over the last few months spent their
pathologists – there are numerous outstanding publications dealing evenings alone, even more frequently than usual.
with the pathologic diagnostic of single genitourinary organs. Its
objective is to give urologists and other interested clinicians an Gregor Mikuz
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Section 1
Renal tumors
Guido Martignoni, Regina Tardanico, Maurizio Pea, Matteo
Brunelli, Stefano Gobbo, and Vincenzo Ficarra

Part 1 Epidemiology, etiology, and clinical history

Part 2 Pathology
Part 3 Tumor genetics
Part 4 Differential diagnosis and use of ancillary methods for diagnosis
Part 5 Principles of staging and grading
Part 6 Pediatric tumors
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Part 1
Epidemiology, etiology, and clinical history

Renal cell carcinoma represents on average over 90% of all malig- roughly half of the cases are now detected because a renal mass
nancies of the kidney that occur in adults in both sexes. Renal cell is incidentally identified on ultrasound (Figure 1.1) or computed
cancer is the seventh leading malignant condition among men and tomography (CT) scan examination (Figure 1.2). It has been reported
the twelfth among women, accounting for 2.6% of all cancers. A that the percentage of incidental renal cancers increased from
1.6:1.0 male predominance exists and the peak incidence is in the 17% between 1976 and 1980, rising to 58% over recent years.5
sixth and seventh decades. About 2% of cases of renal cancer are Moreover, Patard et al proposed classifying patients with renal
associated with inherited syndromes. The American Cancer Society cancer according to the mode of presentation: S1, symptomatic;
estimated 38 890 (24 650 in males and 14 240 in females) new renal S2, patients with local symptoms; and S3, patients with systemic
cancers and 12 840 (8 130 males and 4 710 females) deaths in the symptoms.6 Elevation of the erythrocyte sedimentation rate occurs
United States during 2006.1 in approximately 50% of cases. Renal cell carcinoma may induce
Tobacco smoking is a major cause of kidney cancer and accounts paraneoplastic endocrine syndromes, including pseudohyper-
for at least 39% of all cases in males. Exposure to carcinogenic parathyroidism, erythrocytosis, hypertension, and gynecomastia.
arsenic compounds in industrial processes or through drinking Hypercalcemia without bone metastases occurs in approximately
water increases the risk of renal cancer by 30%. Several other envi- 10% of patients and in nearly 20% of patients with disseminated
ronmental chemicals have been addressed as possible carcinogens, carcinoma. In about 66% of patients, erythropoietin concentration
including asbestos, cadmium, some organic solvents, pesticides, and is elevated. Renal cell carcinoma also is known for presenting as
fungal toxins. Estrogens could be involved in the mechanism that metastatic carcinoma of an unknown primary, sometimes in
induces renal cell carcinoma in overweight and obese individuals.2 unusual sites. Radiologic criteria established by Bosniak assist the
The incidence of renal cell carcinoma in obese people is double that management of renal masses.7,8
of normal individuals and it is also significantly increased in people Ultrasonography is useful for detecting renal lesions and if it
with a history of blood hypertension. Other exposures that have is not diagnostic of a simple cyst, CT before and after intravenous
been addressed are a family history of kidney cancer, birth weight, contrast is required. Plain CT may confirm a benign diagnosis
low consumption of fruits and vegetables, and the use of antihyper- by identifying fat in angiomyolipoma. Lesions without enhance-
tensive drugs other than diuretics.3,4 ment require nothing further, but those with enhancement require
The classic symptomatic presentation includes the triad hema- follow-up at 6 months, 1 year, and then annually.9–16
turia, flank pain, and palpable abdominal mass. Other common pre-
senting features may be not specific, such as fatigue, weight loss, and
anemia. Currently only a few patients present in this manner and

Figure 1.1 Figure 1.2

Ultrasonography: small cortical renal nodule. CT scan after intravenous contrast showing a renal cortical mass.
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Part 2
Pathology

The neoplasms of the kidney are classified by using the World gene activity.20 Both benign and malignant neoplasms are listed as
Health Organization (WHO) 2004 system,17 which represents the well as a diagnostic category named ‘renal cell carcinoma, unclassi-
evolution of the 1997 Consensus Classifications of Heidelberg and fied’, to which can be assigned tumors which do not fit into any of
Rochester.18,19 The WHO 2004 system defines tumor subtypes with the established categories (Figure 1.3).
distinct histopathologic features, clinical behavior, and genetic alter- In the next paragraphs we will describe how to handle the speci-
ations. This classification is critical for clinical management of renal mens from patients with renal tumors, the macroscopic and histo-
tumors and emergence of molecular therapies directed at tumor logic features of the renal neoplasms, and the most important

Rhabdomyosarcoma
Renal cell neoplasms
Malignant fibrous histiocytoma
Clear cell renal cell carcinoma
Hemangiopericytoma
Multilocular clear cell renal cell carcinoma
Osteosarcoma
Papillary renal cell carcinoma
Angiomyolipoma
Chromophobe renal cell carcinoma
Epithelioid angiomyolipoma
Carcinoma of the collecting ducts of Bellini
Leiomyoma
Renal medullary carcinoma
Hemangioma
Xp11 translocation carcinomas
Lymphangioma
Carcinoma associated with neuroblastoma
Juxtaglomerular cell tumor
Mucinous tubular and spindle cell carcinoma
Renomedullary interstitial cell tumor
Renal cell carcinoma, unclassified
Schwannoma
Papillary adenoma
Solitary fibrous tumor
Oncocytoma

Mixed mesenchymal and epithelial neoplasms

Metanephric neoplasms
Metanephric adenoma Cystic nephroma

Metanephric adenofibroma Mixed epithelial and stromal tumor

Metanephric stromal tumor Synovial sarcoma

Neuroendocrine neoplasms
Nephroblastic neoplasms
Nephrogenic rests Carcinoid
Nephroblastoma Neuroendocrine carcinoma
Cystic partially differentiated nephroblastoma others

Hematopoietic and lymphoid neoplasms

Mesenchymal neoplasms
Lymphoma
Clear cell sarcoma
others
Rhabdoid tumor
Congenital mesoblastic nephroma
Ossifying renal tumor of infants Germ cell neoplasms
Leiomyosarcoma
Angiosarcoma
Metastatic neoplasms

Figure 1.3
The WHO classification of tumors of the kidney, 2004 (modified).
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4 Clinical Pathology of Urologic Tumors

tumor-like lesions occurring in the kidney or in the perinephric fat. from areas which are white and gray, and from the periphery to doc-
We divided the renal neoplasms into two groups named frequent ument the interface with the normal renal parenchyma. The renal
tumors and other tumors. In the last one both the rarest tumors of sinus is the fatty compartment located within the confines of the
the WHO 2004 classification and entities reported after the publica- kidney not delineated from the renal cortex by a fibrous capsule.
tion of this classification system have been included. Because it contains numerous veins and lymphatics, invasion into
this compartment may permit dissemination of a tumor otherwise
regarded as renal-limited; more sections including the interface
between the tumor and renal sinus have to be included. Again, addi-
tional sections should include the renal pelvis, renal artery and vein,
Gross and microscopic features ureter, lymph nodes, adrenal, and normal kidney (Figure 1.5).

Handling of renal tumor specimens

The correct handling of the renal tumorectomy (Figure 1.4) or par-
tial and radical nephrectomy by urologists and pathologists is essen- Frequent tumors
tial in order to retrieve all the information useful for diagnosis and
prognosis. The specimen should be brought immediately to the lab- Clear cell renal cell carcinoma
oratory, fresh and without any cut from the operating room, to
avoid any artifact which can cause inadequate sampling of the spec- Clear cell renal cell carcinoma comprises 70% of all renal cell neo-
imen, in particular regarding the evaluation of the surgical margins plasms and its male:female ratio is 2:1.
and the possible neoplastic infiltration of the perinephric fat. If for Grossly, it usually presents as a solitary, well-circumscribed
surgical reasons it is necessary to separate the perinephric adipose (Figure 1.6) or multinodular, yellowish mass with additional gray
tissue, it must be sent indicating the zone of tumoral contact. The and white foci; a pseudocapsule can sometimes be clearly evident
surgical margin in the nephron-sparing surgery specimens and the (Figure 1.7). The yellow part corresponds to well-differentiated
surface of the whole specimen, particularly the areas where the rad- tumor areas, whereas the latter ones are less well differentiated. They
icality is dubious, should be inked by the pathologist (Figure 1.4). are usually solid, but a few cases display a cystic growth pattern.
After inspection of the renal vein, the pathologist should dissect the White sclerotic septa (Figure 1.8), focal calcifications, necrosis, and
specimen obtained by a radical nephrectomy with a bivalving inci- irregular hemorrhage can be seen.21 Under the light microscope,
sion which should pass through the midline of the kidney in the clear cell renal cell carcinoma shows solid, alveolar, and acinar pat-
coronal plane, photograph the bivalved kidney, take fresh neoplastic terns, the most common. The alveolar and acinar structures can be
and normal tissues, and measure the diameter of the tumor. After- dilated and filled with red blood cells. Clear cell renal cell carcinoma
wards some pathologists remove the perirenal fat (Gerota’s fascia) contains a prominent, fine, delicate network of small thin-walled
with blunt dissection from the capsule and, if parts of the capsule are blood vessels (Figure 1.9). The clearing cytoplasm of the neoplastic
adherent to the tumor, dissect around them, leaving them in place cells is the result of an intensive accumulation of glycogen and lipids,
so that they can be taken for histologic examination. Others leave which are dissolved in routine histologic processing. Many tumors
the perirenal fat in place, directly make a series of parallel slabs in the contain neoplastic cells with eosinophilic cytoplasm due to increased
sagittal plane at 2–3 cm intervals, and place the entire specimen in a numbers of mitochondria; this is particularly common in high grade
container of buffered formalin for fixation overnight. The next step
is the gross description of the tumor, which must include side, size,
shape (ball-shaped, polygonal, uni- or multinodular, uni- or multi-
focal), border (sharpness of margins, pseudocapsule), color (yellow,
gray-white, brown, tan-brown, beige), structural features, signs of
regression (necrosis, hemorrhage, scars, pseudocysts), and exten-
sion (restricted to the kidney, infiltration of the perirenal adipose
tissue or the hilar region (renal sinus), macroscopic invasion of hilar
veins or pelvis, presence of lymph nodes and/or adrenal gland).
For histologic study the tissue samples have to be selected and
separately identified from each centimeter of the largest diameter of
the tumor, in particular from areas that differ in color, especially

Figure 1.5
Sampling of renal tumor specimens. 1: Tumor and adjacent
normal renal parenchyma; 2: tumor and adjacent renal sinus
(multiple sections); 3: tumor and adjacent perirenal fat; 4:
section per each particular area that differs in color (hemorrage,
necrosis or scar); 5: normal cortical and medullary renal
parenchyma; 6: section of the hilar region including ureter,
Figure 1.4 branches of small arteries, veins and adipose tissue of the sinus.
Renal tumorectomy: well-demarcated small brown nodule. This section was taken before bevalving the specimen.
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Renal tumors 5

Figure 1.8
Clear cell renal cell carcinoma: tumor with large sclerotic areas.

Figure 1.6
Clear cell renal cell carcinoma: a well-circumscibed, solitary,
and yellowish large tumor.

Figure 1.9
Clear cell renal cell carcinoma: a neoplasm with a solid-acinar
pattern with a prominent, fine, delicate network of small thin-
walled blood vessels.

Figure 1.7
Clear cell renal cell carcinoma: tumor with a thick Rarely, the clear cell renal cell carcinoma presents as a mass
pseudocapsule and a variegation of color from yellowish to thin entirely composed of cysts (Figure 1.10) lined for the most part by a
whitish areas and focal hemorrhage. single layer of clear epithelial cells and septa with no expansile solid
nodules but containing aggregates of epithelial cells with clear cyto-
plasm, so called multilocular cystic renal cell carcinoma. These
tumors are usually of low nuclear grade, confined to the kidney, and
tumors and in neoplastic cells adjacent to necrotic or hemorrhagic associated with an excellent prognosis. Approximately 40 cases have
areas. Sarcomatoid change occurs in 5% of clear cell renal cell carci- been described exclusively in adults, showing a predominance of
nomas and is associated with a poorer prognosis. Stage, nuclear males over females (3:1). Immunohistochemistry can be helpful in
grade, and necrosis are the most important prognostic features of confirming the epithelial nature of the cells within the septa and lin-
this tumor.17,21 ing the cysts.22,23
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6 Clinical Pathology of Urologic Tumors

Figure 1.11
Papillary renal cell adenoma: small cortical tubulo-papillary
neoplasm with a diameter less than or equal to 5 mm.

Figure 1.10
Multicystic clear cell renal cell carcinoma: mass entirely
composed of cysts.

Papillary renal cell neoplasms

Papillary renal cell neoplasms are grossly characterized by a spheri-
cal boundary and a beige to white color. Tumors with a diameter up
to 5 mm are considered adenomas (Figure 1.11). They are often
incidental findings and occur in up to 23% of autopsy patients. The Figure 1.12
larger tumors are viewed as carcinomas, comprise 15% of all of sur- Papillary renal cell carcinoma exhibiting a central hemorrhage.
gically removed renal cell neoplasms, and the male to female ratio is
2:1. They can exhibit central necrosis resulting from a poor vascular
supply and frequent hemorrhages (Figure 1.12). In some cases this
feature can be so extensive as to mimic a cyst both radiologically
and grossly. has been described for type 1 papillary renal cell carcinoma when
Microscopically, papillary renal cell neoplasms are characterized compared with type 2.27,28 A papillary renal cell carcinoma entirely
by papillary or tubulo-papillary architecture.24 The epithelial neo- composed of oncocytes has been described.29 This subset of papillary
plastic cells line a delicate fibrovascular core in which aggregates of tumors shows clinico-pathologic features different from type 1 and
foamy macrophages can be found. The core can be expanded by type 2 papillary renal cell carcinomas and has been proposed to be a
edema. In carcinomas cholesterol crystals, necrosis, and hemor- third group, being intermediate between type 1 and type 2.
rhage are frequently seen and hemosiderin granules may be present Sarcomatoid dedifferentiation is seen in approximately 5% of
in macrophages, stroma, and tumor cell cytoplasm. papillary renal cell carcinomas and has been associated with both
Two well-recognized morphologic types of papillary renal cell type 1 and type 2 tumors.30,31
carcinomas have been described. Type 1 tumors have papillae cov-
ered by small cells with scanty cytoplasm, arranged in a single layer
on the papillary basement membrane with low nuclear grade
(Figure 1.13); type 2 tumors are composed of cells with higher
Chromophobe renal cell carcinoma
nuclear grade, eosinophilic cytoplasm, and pseudostratified nuclei Chromophobe renal cell carcinoma accounts for 5% of all cases of
on papillary cores (Figure 1.14). Type 1 tumors are more frequently surgically removed renal epithelial tumors, without any difference
multifocal. Psammoma bodies are common.19,25,26 Longer survival between males and females.32
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Renal tumors 7

Figure 1.13
Papillary renal cell carcinoma: type 1 tumors have papillae
covered by small cells with scanty cytoplasm, arranged in a
single layer on the papillary basement membrane, and low
nuclear grade.
Figure 1.15
Chromophobe renal cell carcinoma: solid well-circumscribed
mass with a light brown color on the cut surface.

Figure 1.14
Papillary renal cell carcinoma: type 2 tumors are composed of
cells with higher nuclear grade, eosinophilic cytoplasm, and
pseudostratified nuclei on papillary cores. Figure 1.16
Chromophobe renal cell carcinoma: microscopically shows a
solid, ‘cobblestone’ growth pattern whereas the acinar
architecture surrounded by a rich vascular network as seen in
Grossly, it is a solid, well-circumscribed neoplasm with a light clear cell renal cell carcinoma is lacking. The cytoplasm of a
brown color on the cut surface (Figure 1.15). The morphologic fea- typical chromophobe is pale pink and flocculent and the
tures of chromophobe renal cell carcinoma include a solid, ‘cobble- peripheral portion of the cytoplasm shows a variable degree of
stone’ growth pattern, whereas the acinar architecture surrounded granularity and eosinophilia, resulting in an accentuation of the
by a rich vascular network as seen in clear cell renal cell carcinoma is cellular membrane. A perinuclear ‘halo’ may be observed.
lacking. A tubular architecture may be occasionally seen.33 Focal cal- Nuclei range from vesicular to wrinkled and can exhibit
cifications and broad fibrotic septa are frequently present. The cyto- pleomorphism. The neoplastic cells can display binucleation.
plasm of a typical chromophobe is pale pink and flocculent and
the peripheral portion of the cytoplasm shows a variable degree of
granularity and eosinophilia, resulting in an accentuation of the cel- figures can be found in a variable amount ranging from none to
lular membrane. A perinuclear ‘halo’ may be observed (Figure 1.16). twenty-five
50 high power fields.34–39
Nuclei range from vesicular to wrinkled and can exhibit marked At electron microscopy chromophobe renal cell carcinoma is
pleomorphism. The neoplastic cells can display binucleation. Mitotic typically characterized by a cytoplasm containing scant numbers
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8 Clinical Pathology of Urologic Tumors

Figure 1.17
Chromophobe renal cell carcinoma: eosinophilic variant
showing neoplastic cells with prevalent degree of granularity
and eosinophilia.

of mitochondria, which have tubulo-vesicular cristae, and by the

Figure 1.18
Collecting duct carcinoma (so-called Bellini duct carcinoma):
presence of innumerable 150–300 micron microvesicles scattered
large gray-whitish bulging tumor arising from the medulla.
between the mitochondria.33,40,41 These microvesicles are responsible
for the perinuclear halo and flocculent cytoplasm in the chromo-
phobic neoplastic cells and can be used as a diagnostic finding.41
In 1988, 10 cases of eosinophilic variant out of 32 chromophobe
renal cell carcinomas were identified.34,42 This morphologic variant
represents roughly 10% of this histotype (Figure 1.17). Chromo-
phobe renal cell carcinoma is a low-grade malignancy; however, sar-
comatoid transformation occurs in 8% of cases.
A diffuse cytoplasmic staining reaction with Hale’s iron colloid
stain has, for a long time, been considered a characteristic feature of
this special tumor type only,43 but it has recently been observed in
acquired cystic disease-associated renal cell carcinomas.44

Collecting duct carcinoma (so-called

Bellini duct carcinoma)
The group of tumors with collecting duct differentiation is undergo-
ing considerable change and redefinition. The recommendation is
to restrict the term ‘collecting duct carcinoma’ to the whitish and
firm tumors grossly located in the medulla or central parts of the Figure 1.19
kidney. They are usually large and infiltrative with extension into the Collecting duct carcinoma: microscopically, it shows highly
perinephric fat and invasion of the renal pelvis (Figure 1.18). Histo- irregular duct-like structures, nests, and cords of cells in an
logically, they are high-grade and highly aggressive carcinomas with abundant desmoplastic stroma.
papillary ductal architecture, stromal desmoplasia, and granulocytic
infiltration (Figure 1.19). Lymph node metastases are common.45
Some of them are associated with sickle cell trait and are grouped
separately under the term medullary carcinoma.46–48 The oncocytoma is a well-circumscribed large tumor with a stellate
central scar and is a uniform mahogany brown color (Figure 1.20).
Foci of hemorrhage can be observed, but necrosis is consistently
absent.
Oncocytoma Microscopically, oncocytoma displays a compact solid or nesting
Renal oncocytomas are benign neoplasms. They comprise 5% of arrangement of large cells in an edematous and hyalinized stroma.
adult renal epithelial tumors in surgical series and the male to female Neoplastic cells have abundant granular eosinophilic cytoplasm,49
ratio is 2:1. reflecting the presence of the numerous mitochondria visible on
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Renal tumors 9

Figure 1.22
Renal oncocytoma: a tubulo-cystic pattern of growth can be
observed in a few cases.

Figure 1.20
Renal oncocytoma: well-demarcated solid nodule with a tan Metanephric adenoma
color appearance and a stellate central scar. The family of metanephric neoplasms comprises a spectrum of lesions
that are derived from the metanephric blastema such as metanephric
adenoma, metanephric adenofibroma, and the metanephric stromal
tumor.
Metanephric adenoma is the most frequently occurring member
of this family. It is a benign tumor which occurs most commonly in
women during their fifth decade of life. Approximately 10% of
patients with this neoplasm present with polycythemia due to
increased erythropoietin production.
Grossly, this tumor presents as a single, solid, well-circumscribed
nodule with light brown to sandy cut surfaces of glassy quality
(Figure 1.23). The tumors are sharply demarcated from adjacent
parenchyma; hemorrhagic ones can be present. Necrosis and soften-
ing are not found, although cystic regression may occur in the center.
Histologically, metanephric adenoma consistently lacks a fibrous
pseudocapsule. It is composed of densely packed, small, neoplastic
cells with overlapping nuclei and invisible cell borders in solid-
appearing areas, turning to a polar orientation in areas of more dif-
ferentiated tubular, tubulo-papillary, or glomeruloid structures. The
nuclei are innocent looking and mitoses are uncommon (Figure 1.24).
It may contain psammoma bodies, especially in the peripheral scle-
rotic zones.55–57
Figure 1.21
Renal oncocytoma: this tumor displays a compact solid or
nesting arrangement of large cells with abundant granular
cytoplasm; the nuclei of neoplastic cells are regular and round, Angiomyolipoma
with a nucleolus often evident.
Angiomyolipoma is the most common mesenchymal neoplasm of
the kidney. It is classically composed of a variable mixture of
fat, spindle and epithelioid smooth muscle cells, and abnormal
ultrastructural analysis. The nuclei of renal oncocytoma cells are thick-walled blood vessels. The perivascular epithelioid cell is con-
regular and round, with a nucleolus often evident (Figure 1.21). sidered to be the cell of origin for this and other related tumors58
Rarely, occasional degenerative bizarre nuclei or scattered nests of (Figure 1.25). Angiomyolipoma has, for a long time, been considered
small cells, so called oncoblasts, can be found. A tubulo-cystic pat- to be a hamartoma rather than a true tumor, but its clonal nature
tern of growth can be prevalent in a few cases (Figure 1.22). The has been recently demonstrated. Angiomyolipoma can be sporadic
extension of oncocytoma cells into perirenal adipose tissue can or occurring in patients with tuberous sclerosis, an inherited syn-
occur in rare cases.50–52 drome. In patients with tuberous sclerosis, renal angiomyolipomas
The iron colloidal staining in renal oncocytoma is weak, distrib- are found in both sexes, in the third and fourth decades of life; they are
uted in focal areas, and in the form of fine, dust-like granules;43 some usually asymptomatic, bilateral, small, and multifocal (Figure 1.26).59
authors have reported an apical positivity with Hale’s colloidal iron Sporadic angiomyolipomas occur in older patients, in the fourth to
staining in a group of renal oncocytomas.53,54 sixth decades of life, with a female predominance; they are single,