SP Web 7\26\09
Case 1
A 55 year old man was noted to have a bladder mass and underwent a transurethral
resection.
Choose the correct diagnosis:
A.
Infiltrating high grade urothelial carcinoma with rhabdoid features
B.
Infiltrating high grade carcinoma with oncocytic features
C.
Paraganglioma
D.
Rhabdomyosarcoma
Answer: C
Histological description: Architecturally, the tumor consists of infiltrating irregular nests
associated with a fibroblastic reaction. The tumor cells have abundant amphophilic
cytoplasm which in some areas has a granular nature. The tumor shows moderate to
marked pleomorphism. However, much of the atypia appears degenerative in nature
lacking mitotic figures.
Differential diagnosis: The predominant differential diagnosis in this case is infiltrating
high grade urothelial carcinoma versus paraganglioma. In contrast to the usual
paraganglioma of the bladder or paraganglioma seen in other sites, this case is difficult in
that it lacks in many areas of the classic nesting (zellballen) appearance. A clue to the
correct diagnosis of paraganglioma is that the cells have abundant amphophilic granular
cytoplasm which would be distinctly unusual for urothelial carcinoma. Furthermore, the
nature of the atypia is typical for endocrine tumors consisting of nuclei with
hyperchromatic, smudgy chromatin lacking mitotic figures. Focally, one can appreciate a
nesting appearance separated by fine thin vessels although it is not prominent. It is
critical to make a distinction between paraganglioma of the bladder versus urothelial
carcinoma as the treatment could differ. With paraganglioma, the lesion lacks
multifocality in contrast to urothelial carcinoma such that the goal is just to remove the
tumor itself. If the tumor is located in the dome, one can get by with a partial cystectomy
as compared to a radical cystectomy for urothelial carcinoma. In many cases, the
diagnosis of paraganglioma is known by the clinicians preoperatively due to
manifestations of catecholamine secretions. Classically, many patients have
hypertension, micturition attacks consisting of palpitation and syncope upon urination.
However, a minority of cases may be clinically silent in terms of features relating to
catecholamine secretions, where the diagnosis rests on the histopathological
examination. Confirmation of the diagnosis of paraganglioma can be made with
immunoreactivity to neuroendocrine markers such as synaptophysin and chromogranin
with negative immunostaining to various keratins. Immunostaining for S100 variably
shows sustentacular cells surrounding tumor nests. One cannot predict the malignant
behavior of paragangliomas based on the morphology with approximately 10-15%
eventually demonstrating metastases.
Case 2
A 30 year old man was noted to have a testicular tumor and underwent orchiectomy.
Choose the correct diagnosis:
A.
Yolk sac tumor
B.
Teratoma
C.
Adenocarcinoma arising in a teratoma
D.
Metastatic adenocarcinoma with extensive vascular invasion
Answer: A
Histological description: The tumor consists of glandular structures situated within a
loose fibrous background. The glands are remarkable for areas where nuclei are lined
up midway in the cytoplasm with prominent sub and supranuclear clear vacuoles.
The nuclei are moderately atypical yet do not show marked pleomorphism.
Differential diagnosis: Although this lesion is composed of glands, it is not overtly
pleomorphic as one would expect with an adenocarcinoma arising in a teratoma or a
metastatic adenocarcinoma to the testis. The spaces surrounding many of the tumor
nests lack endothelial lining and appear to be retraction artifact. The major
differential diagnosis is between a malignant teratoma and glandular variant of yolk
sac tumor. Typically, glands of teratoma are surrounded by smooth muscle trying to
recapitulate normal structures such as respiratory mucosa or intestinal glands. In
contrast, glands of yolk sac tumor are present within fibrous tissue, lacking such an
investment by smooth muscle. The other typical feature seen in this case of glandular
variant of yolk sac tumor is the presence of prominent subnuclear vacuoles in some of
the glands reminiscent of day 16-17 secretory endometrium. Immunonistochemistry
was performed in this case demonstrating the glands were strongly positive for alphafeto-protein and negative for epithelial membrane antigen consistent with the
diagnosis of yolk sac tumor.
Case 3
A 66 year old man was noted to have elevated serum PSA levels and underwent a
prostate needle biopsy.
Choose the correct diagnosis:
A.
Adenocarcinoma of the prostate, Gleason score 3+3=6
B.
Adenocarcinoma of the prostate, Gleason score 3+4=7
C.
Basal cell hyperplasia
D.
Reactive benign prostate glands with acute inflammation
Answer: D
Histological description: Focally, within the biopsy there is an area of crowded
prostatic glands. At higher magnification, the glands have enlarged nuclei, some
with visible nucleoli. Most of the glands have a moderate amount of cytoplasm and
within many of the lumens is associated acute inflammation.
Differential diagnosis: The differential diagnosis in this case rests between small
focus of adenocarcinoma of the prostate versus reactive prostate glands associated
with inflammation. One must be extremely cautious in diagnosing limited
adenocarcinoma of the prostate even in the presence of a few neutrophils within
glandular lumina. Even with relatively trivial inflammation one can see prominent
cytologic atypia with reactive nuclei containing enlarged vesicular nuclei with
enlarged prominent nucleoli mimicking adenocarcinoma. In these cases, it is
imperative to perform stains for basal cells as was done in this case.
Immunohistochemistry demonstrates presence of both p63 and high molecular weight
cytokeratin in all of the crowded glands ruling out adenocarcinoma of the prostate.
Case 4
A 70 year old man was noted to have a 2 cm lesion in the kidney. A needle biopsy
was performed.
Choose the correct diagnosis:
A.
Metanephric adenoma
B.
Papillary adenoma
C.
Adult Wilms’ tumor
D.
Solid variant of papillary renal cell carcinoma
Answer: D
Histological description: An initial slide received in consultation on this case shows
fragments of a very basophilic neoplasm consisting of solid sheets of cells, tubules
and small papillae. The tumor had very scant cytoplasm with uniform benign
appearing nuclei. Focally, one of the fragments contained lighter eosinophilic
cytoplasm with more prominent papillary formation. Immunostains were performed
with CK7 showing diffuse strong positivity with negative stains for WT-1.
Differential diagnosis: The differential diagnosis in this case predominantly rests
between metanephric adenoma and solid variant of papillary renal cell carcinoma. In
this case, the distinction is critical as if the lesion was metanephric adenoma, a totally
benign lesion, the clinicians were planning on leaving the lesion untreated. However,
if the lesion was solid variant of papillary renal cell carcinoma, a partial nephrectomy
was going to be performed. Typically, the best distinction between metanephric
adenoma and solid variant of papillary renal cell carcinoma is the low power color.
Metanephric adenomas tend to have a very “blue” appearance due to scant cytoplasm
where solid variant of papillary renal cell carcinoma with their abundant cytoplasm
has a more eosinophilic appearance at low magnification. This case is particularly
difficult in that much of the tumor has a more basophilic, where the low and high
magnification appearance is highly suggestive of metanephric adenoma. However,
focal areas show more abundant cytoplasm which is more typical of solid variant of
papillary renal cell carcinoma. Hybrid lesions between metanephric adenoma and
solid variant of papillary renal cell carcinoma have not been described such that
immunohistochemistry was performed to help resolve this dilemma. Metanephric
adenomas are strongly positive for WT-1 and negative for CK7, whereas papillary
renal cell carcinomas have the opposite staining pattern. In this case the strong
staining for CK7, negative staining for WT-1, along with areas of the tumor showing
lighter cytoplasm and more prominent papillary formation is diagnostic of papillary
renal cell carcinoma. This case emphasizes that before diagnosing a lesion as
metanephric adenoma the entire lesion should be classic for that entity and if any
areas have somewhat more abundant cytoplasm immunohistochemistry should be
performed to verify the diagnosis.
Case 5
A 35 year old male was noted to have a bladder tumor. A transurethral resection was
performed.
Choose the correct diagnosis:
A.
Metastatic adenocarcinoma of the prostate
B.
Infiltrating mucinous adenocarcinoma of the bladder
C.
Metastatic adenocarcinoma from the rectum
D.
Cystitis glandularis, intestinal type
Answer: D
Histological description: The lesion consists of numerous glands lined by columnar
cells, many of which have the appearance of goblet cells. The nuclei are uniform,
basally situated and lack overt atypical features. Mitotic figures are difficult to find.
The stroma surrounding the glands is myxoid and mucinous. In areas, the urothelium
has been replaced by squamous metaplasia.
Differential diagnosis: The pattern seen in this case does not resemble any of the
morphology seen within adenocarcinoma of the prostate. One cannot distinguish
morphologically between infiltrating adenocarcinoma from the colon versus
adenocarcinoma of the bladder. Consequently, the differential diagnosis in this case
rests between infiltrating adenocarcinoma whether from bladder of colon versus florid
intestinal type cystitis glandularis. Infiltrating adenocarcinomas of the bladder are
entirely analogous with the full spectrum adenocarcinomas seen within the
gastrointestinal tract. This includes enteric, signet ring cell, and colloid patterns.
With rare exception, adenocarcinomas of the bladder have overt cytlogic atypia with
a desmoplastic stromal reaction where it is easy to identify the glands as malignant.
In contrast, glands within the current specimen are lined by cytologically bland
epithelium and it is only the pattern of crowded glands surrounded by mucin
extravasation that architecturally resembles carcinoma. However, cystitis glandularis
of the intestinal type may show mucinous extravasation and rarely even involves the
muscularis propria. Consequently, all of the findings in the current case are classic
for cystitis glandularis, intestinal type with no features worrisome for
adenocarcinoma. It is critical to recognize that cystitis glandularis, intestinal type
may on occasion make a mass lesion that clinically will be strongly suspicious for a
neoplasm. Despite the reservations raised by the urologists, it is critical to reassure
them that this lesion is benign. On rare occasions, one may see adenomatous foci
within cystitis glandularis, intestinal type and in those cases it is recommended that
complete but conservative excision be performed to rule out a very rare co-existing
infiltrating adenocarcinoma.
Case 6
A 75 year old man was noted to have a mass in the epididymis.
Choose the correct diagnosis:
A.
Papillary cystadenoma
B.
Metastatic renal cell carcinoma
C.
Adenocarcinoma of the epididymis
D.
Rete testis hyperplasia
Answer: A
Histological description: The tumor consists of lobules composed of papillary
structures lined by cells with abundant to clear cytoplasm. Nuclei appear uniform and
small without atypia or mitotic figures. In areas, the tumor is seen projecting within
small cystic structures.
Differential diagnosis: Approximately 50% of cases of papillary cystadenoma of the
epididymis are associated with von Hippel-Lindau disease. Especially in the setting
of von Hippel-Lindau disease, the differential diagnosis is between papillary
cystadenoma and metastatic renal cell carcinoma as patients with von Hippel-Lindau
disease are at increased risk of having renal cell carcinoma. Some cases of papillary
cystadenoma are composed of small solid nests of cells separated by a fine, thin
vasculature where they can closely resemble renal cell carcinoma. Other areas will
show a more papillary configuration with the same clear cytoplasm that is more
typical of papillary cystadenoma and would be unusual in clear cell renal cell
carcinoma. In the current, virtually the entire lesion is composed of papillary clear
cells which again would be distinctly unusual for renal cell carcinoma. The lack of
cytologic atypia, while it can be seen in metastatic renal cell carcinoma, would also
be unusual. Immunohistochemically, papillary cystadenoma of the epididymis tends
to be strongly positive for CK7, negative for RCC with most cases negative for
CD10. This staining profile contrasts with that seen in clear cell renal cell carcinoma
which is typically negative for CK7 and immunoreactive for RCC and CD10.
Caution must be emphasized when using immunohistochemistry for PAX-2 as it can
be seen both in papillary cystadenoma and clear cell renal cell carcinoma. A few
cases of primary adenocarcinoma of the epididymis have been reported and these
lesions are overtly malignant with greater cytologic atypia and an ifiltrative growth
pattern. Papillary cystadenomas of the epididymis are entirely benign, with any
morbidity or mortality relating to other manifestations of von Hippel-Landau disease,
if present.