ONCOCYTOMA
METASTATIC RENAL CELL CARCINOMA
INVERTED UROTHELIAL PAPILLOMA
SCHWANNOMA
FOLLLICULAR VARIANT , PAPILLARY THYROID CARCINOMA
INTRAVASCULAR LYMPHOMA
Case #1: Oncocytoma
Clinical History: 53-year-old male with a left kidney mass.
Choose the correct diagnosis:
A.
B.
C.
Oncocytoma
Renal cell carcinoma with oncocytic features
Chromophobe renal cell carcinoma
Histology: The tumor consists of new eosinophilic cells with small round and regular
nuclei arranged in nests, cords and tubules. The background shows myxoid changes and
focal fibrous scar. On high magnification, the nuclei are all uniformly round and show
bland cytology without significant atypia. Small nucleoli may be seen in some of the
cells.
Discussion: Oncocytomas are benign renal neoplasms that are derived from intercalated
cells. Grossly, the tumor appears as a mahogany, brown mass with a central scar.
Histologically, the tumor is composed of eosinophilic cells with bland cytology, having
small, round, regular nuclei. The tumor cells are often arranged in nests, cords or tubules
in a myxoid background. Occasional degenerative atypia or pleomorphism may be seen,
however, oncocytomas will not show any areas of papillary formation, necrosis or clear
cells. Oncocytomas may occasionally infiltrate perirenal soft tissue, however, this does
not affect the prognosis. Electron microscopy will show that the cells are packed with
mitochondria, which accounts for their eosinophilic appearance.
Oncocytomas may resemble chromophobe renal cell carcinomas, in that they have
prominent eosinophilic cytoplasm, however, oncocytomas usually show densely
eosinophilic cytoplasm throughout the entire lesion and lack the pale appearance seen in
many of the cells in a chromophobe renal cell carcinoma. Chromophobe renal cell
carcinomas also show perinuclear halos, and nuclear irregularity and pleomorphism,
which would not be seen in oncocytomas. Chromophobe renal cell carcinomas also have
distinct cell borders, which often resemble plant cells, which is a feature not seen in
oncocytomas. A Hales colloidal iron stain, which stains for acidic mucin, can be helpful
in cases where it is difficult to tell the two lesions apart. Chromophobe renal cell
carcinomas would show intense and diffuse staining within the cytoplasm of the tumor
cells, while an oncocytoma is usually negative or only shows luminal staining within
some of the tubules, for Hales colloidal iron. Oncocytomas are differentiated from renal
cell carcinomas with oncocytic features by the lack of cytologic atypia. Also, in renal
cell carcinomas with oncocytic features, there are often areas of more conventional renal
cell carcinomas showing clear cells.
References:
Am J Surg Pathol 1997; 21:1-12.
Am J Surg Pathol 2000; 24:1247-56.
CASE 2: Renal cell carcinoma, metastatic to adrenal
Clinical History: 63-year-old female with adrenal mass
Choose the correct diagnosis:
A.
B.
C.
D.
E.
Adrenal cortical adenoma
Adrenal cortical carcinoma
Metastatic renal cell carcinoma
Pheochromocytoma
Metastatic adenocarcinoma
Histology: The lesion consists of a circumscribed area of clear cells growing in a nested
and tubular pattern. The nuclei show some variation in size and shape, some with
nucleoli. Compared to the adjacent normal adrenal tissue, the tumor cells are clear rather
than vacuolated and granular.
Discussion: The lesion in the adrenal raises a differential diagnosis of primary adrenal
neoplasm and metastatic lesions to the adrenal gland. The lack of necrosis, nuclear
anaplasia and vascular invasion, and the small size of the lesion make an adrenal cortical
carcinoma unlikely. The clear cells raise the possibility of a metastasis from the kidney,
which would be important to differentiate from an adrenal cortical adenoma. To
unequivocally establish the diagnosis, immunohistochemical stains need to be performed.
RCC, CD10, CAM 5.2, EMA are all expected to be positive in renal cell carcinoma and
negative in adrenal cortical lesions, while inhibin and Melan-A should be positive in
adrenal cortical lesions and negative in renal cell carcinoma. Pheochromocytomas arise
from the adrenal medulla and usually shows pleomorphic cells with basophilic
cytoplasm, unlike the clear cells seen in this case, neuroendocrine markers, such as
chromogranin would also be positive, in contrast to the other entities in the differential.
Case #3: Inverted urothelial papilloma
Clinical History: 64-year-old male with hematuria.
Choose the correct diagnosis:
1. Papillary urothelial neoplasm of low malignant potential with inverted growth
pattern
2. Low grade papillary urothelial carcinoma with inverted growth pattern
3. High grade papillary urothelial carcinoma with inverted growth pattern
4. Inverted urothelial papilloma
Histology: The tumor shows an inverted growth pattern, no papillary projections are
seen. The lesion has a smooth, well circumscribed base. The cells are bland, show no
mitosis and are arranged in inter-anastamosing cords.
Discussion: Inverted urothelial papilloma is a rare benign tumor of the urinary bladder.
Cystoscopically, it appears as solitary raised, pedunculated or, rarely, polypoid lesions
with a smooth surface. Tumor size varies from small (<3 cms) to large lesions measuring
up to 8 cms. Most lesions are solitary and present with hematuria.
Histologically, the classic lesion shows cords and trabeculae of cells arising from
a smooth surface and invaginating into the lamina propria. The periphery of the cords is
composed of darker cells that are often palisade, while the central portions show maturing
cells occasionally with superficial cells lining central lumenal spaces. The surrounding
stroma is fibrotic and non-reactive without inflammation. Cytologic atypia is minimal to
absent, although occasionally atypia of the degenerate type may be seen focally. Mitotic
figures are rare, and if present, only seen at the periphery of the trabeculae. The
trabeculae are orderly, of relatively uniform width, with considerable ramifications and
interanastomosis.
The lack of cytologic atypia, mitoses, architectural disorganization and and
exophytic component rules out a papillary urothelial carcinoma with inverted growth
pattern. While rare papillary urothelial neoplasms of low malignant potential may show
only an inverted growth pattern, there would be some cytologic atypia and would not
show the interanastamosing cords of cells with palisading nuclei seen in a benign
inverted papilloma.
Case #4 Schwannoma
Clinical History: 52-year-old male with an intracranial mass.
Choose the correct diagnosis:
1. Malignant peripheral nerve sheath tumor
2. Neurofibroma
3. Schwannoma
4. Meningioma
Histology: The tumor is an encapsulated lesion, which grows eccentrically along the
periphery of a nerve. The cellular tumor consists of spindle cells arranged in short
bundles or interlacing fascicles and foci of nuclear palisading and whirling of cells can be
seen. In some areas, the spindle cells form long sweeping fascicles. Mitotic figures are
not seen. The vessels within the tumor show perivascular hyalinization. Focal small
cystic areas are seen.
Discussion: Classic schwannomas show a mixture of Antoni A and B areas. Antoni A
areas are cellular areas composed of compact spindle cells arranged in short bundles or
interlacing fascicles. In these cellular areas, there may be nuclear palisading and whirling
of cells. Characteristic Verocay bodies may be seen. Antoni B areas are less orderly and
less cellular areas composed of loose matrix with foci of microcystic change and
inflammatory cells. This lesion lacks atypia and shows no mitoses, arguing against a
malignant diagnosis. Neurofibromas may show cellular areas that resemble Antoni A
areas of a schwannoma, however, unlike schwannomas, neurofibromas are not
encapsulated and small nerves can usually be demonstrated within the lesion.
Meningiomas can be confused with schwannomas, as cellular whirling areas can be seen
in both lesions. Immunohistochemical stains can be helpful to differentiated between the
two entities. Schwannomas are positive for S100 and negative for EMA, while
meningiomas show the opposite staining pattern.
CASE #5 FOLLICULAR VARIANT OF PAPILLARY THYROID CARCINOMA
Clinical History: 33 year old woman with goiter.
Choose the correct diagnosis:
1.
2.
3.
4.
Papillary thyroid carcinoma
Adenomatoid nodule
Follicular carcinoma
Follicular adenoma
Histology: The tumor a well circumscribed nodule that appears distinct from the
remainder of the thyroid. On low magnification, most of the tissue in the nodule appears
similar to the surrounding normal thyroid. Focally, within the nodule, paler more
crowded areas are seen. On higher magnification the nuclei in these crowded areas are
noted to be overlapping, large, and optically clear. Nuclear grooves are also occasionally
observed. Other areas with rudimentary papillary formations can be seen.
Discussion: A well-circumscribed nodule is seen which contains predominantly bland
follicles. Scattered throughout this nodule are areas with features including enlargement
of the nuclei, clearing of the chromatin, nuclear overlapping and nuclear grooves. These
features are diagnostic of papillary carcinoma and are helpful in distinguishing this
nodule from follicular adenoma and graves disease, which would have more benign
appearing nuclei. Since multiple areas with these classic features for papillary carcinoma
were seen scattered throughout the nodule, the diagnosis of follicular variant of papillary
thyroid carcinoma was made, rather than papillary microcarcinoma arising in an
adenomatoid nodule.
Papillary carcinoma of the thyroid is associated with the RET oncogene. The overall
prognosis for patients with papillary cancer is excellent. Extra-thyroid extension into soft
tissues of the neck is seen in approximately twenty five percent of patients. Involvement
of cervical lymph nodes is very common and does not adversely affect the prognosis.
Factors that are associated with a worse prognosis are age greater than forty years, extra
thyroid extension, large tumor size, multicentricity, distant metastasis, and presence of
anaplastic foci.
CASE #6 intravascular lymphoma
Clinical History: 66 year old man with unsteady gait
Choose the correct diagnosis:
1. Metastatic carcinoma
2. Intravascular lymphomatosis
3. Brain infarction
Histology: The brain parenchyma is unremarkable except for focal areas of necrosis.
Large atypical cells are seen within and confined to the blood vessels within the brain
parenchyma. CD 3 and CD 20 stains show that the large cells are B-cells.
Discussion: Intravascular lymphomatosis (IVL) is a rare angiotrophic large cell
lymphoma producing vascular occlusion of arterioles, capillaries, and venules. The
majority of cases reported in the literature are case reports and small series. IVL is
associated with an aggressive course with survival reported in months, and many patients
are diagnosed at the time of autopsy. Antigenic phenotyping shows that these
lymphomas are mostly of B cell type, and less commonly T cell or Ki-1 lymphomas. The
central nervous system and skin are the two most commonly affected organs; patients
usually present with progressive encephalopathy with mental status changes and focal
neurological deficits and skin petechia and discoloration. Fever of unknown origin is
another common presentation. Other organs can be involved, including adrenal glands,
lungs, heart, spleen, liver, pancreas, genital tract, and kidneys. Bone marrow, blood,
cerebrospinal fluid, and lymph nodes are typically spared. Neoplastic lymphoid cells
mainly lodged in the lumina of small vessels in many organs, but infarction is most
common in the CNS. Our patient presented with mental status changes, distal extremity
myopathy and an elevated sedimentation rate without mass lesion in the CNS and was
presumed to have a rheumatologic disorder, such as vasculitis.
The histologic features of the brain biopsy are not likely to be confused with other
entities. The confinement of the neoplastic cells within blood vessels, along with
immunohistochemical stains proving B-cell phenotype establishes the diagnosis. The
large atypical cells raise a possibility of metastatic carcinoma, however the discohesive
appearance and lack of involvment of the brain parenchyma make the diagnosis unlikely.
References:
Mod Pathol. 1988 Nov;1(6):444-52
J Clin Pathol. 2003 Jun;56(6):468-70.