Case 3 - Pathology

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SP web 52007
A 77 year female was noted to have a bladder lesion on the posterior wall.
Choose the correct diagnosis:
A.
B.
C.
D.
Signet ring cell carcinoma
Clear cell (mesonephric) adenocarcinoma
Nephrogenic adenoma
Metastatic thyroid carcinoma
Answer: C
Histological description:
There are two pieces of tissue removed. One piece consists of tubules lined by cuboidal
flattened epithelium with dense pink secretions resembling thyroid follicles. Many of the
follicles have associated intraluminal acute inflammation. The other piece of tissue
shows a mixture of small tubules and structures resembling signet ring cells containing
blue tinged mucinous secretions. Some of the small tubules and signet ring-like
structures have a hyaline rim of collagen surrounding them. Both pieces of tissue on the
surface are lined by flat cuboidal epithelium.
Discussion:
This is a classic case of nephrogenic adenoma. Nephrogenic adenoma may have multiple
histological patterns. Some of them, like the signet ring-like cell pattern, may be
confused with adenocarcinoma, yet other patterns will typically be present, providing a
clue to the correct diagnosis. In this case the thyroid-like tubules are particularly striking
and is a characteristic feature of nephrogenic adenoma not seen with any of its
mimickers. The signet-ring-like structures represent small tubules lined by flattened
epithelium which depending on the plane of section may show only one nucleus
resembling a signet ring cell carcinoma. Distinguishing it from signet ring cell carcinoma
requires finding of slightly larger similar tubules with more than one nucleus, the hyaline
rim of connective tissue surrounding some of these structures, and the other more
characteristic features of nephrogenic adenoma seen elsewhere in the lesion. Features
that should not be seen in nephrogenic adenoma include mitotic figures or necrosis.
While I have seen rare cases with very focal clear cells and small solid nest of cells these
are distinctly uncommon and more typically seen in malignant tumors resembling
nephrogenic adenoma such as clear cell (mesonephric) adenocarcinoma.
Case 2
A 71 year old male underwent a transurethral resection of the prostate for lower urinary
tract symptoms.
Choose the correct diagnosis:
A. Basal cell hyperplasia.
B. Basal cell carcinoma.
C. Adenocarcinoma of the prostate.
Answer A.
Histological description
This entire TURP consisting of 12 slides was entirely involved by the process illustrated.
There are numerous crowded medium sized glands some arranged in a lobular
configuration and others appearing more diffusely infiltrative. The glands show an inner
layer of cells with abundant lightly eosinophilic cytoplasm associated with benign
appearing nuclei. Many of the glands contain dense pink secretions. Exterior to the inner
secretory cell lining is a proliferation of cells with enlarged nuclei containing very
prominent nucleoli with scant cytoplasm. These cells range from one cell thick to several
cells in thickness. These nuclei are blue-gray in contrast to the more violet appearing
nuclei of the overlying secretory cells. Focally within this process there are occasional
cribriform glands with a similar inner lining of benign secretory cells and an exterior
proliferation of cells with enlarged nuclei containing prominent nucleoli.
Within the cribriform lumina there are basophilic secretions.
Discussion:
This pattern of basal cell hyperplasia is particularly difficult to distinguish from
adenocarcinoma of the prostate. The more easily recognizable form of basal cell
hyperplasia consists of tubules with a more prominent piling up of basal cell layer
including solid nests of basal cells, distinctive from adenocarcinoma of the prostate. In
contrast, this case shows only minimal piling up of the basal cell layer along with a
crowded glandular proliferation more closely mimicking prostate cancer. The key
distinguishing feature is the two distinct cell layers with both a basal layer and an
overlying secretory cell layer. Basal cells may show prominent nucleoli in both normal
basal cells as well as in basal cell hyperplasia, as seen in the current case. This case also
shows focal cribriform basal cell hyperplasia which could mimic one of the patterns of
basal cell carcinoma. However the presence of the overlying secretory cell layer both in
the cribriform glands as well as in the tubular glands is not a feature of basal cell
carcinoma. Furthermore, basal cell carcinoma tends to show a desmoplastic stromal
reaction which is lacking in the current case. Despite the extensive nature of this process,
this lesion is entirely benign and merely a mimicker of prostate cancer.
Case 3
An 81 year old female was noted to have a bladder lesion.
Choose the correct diagnosis:
A.
B.
C.
D.
Papillary urothelial hyperplasia.
Urothelial dysplasia with early papillary formation.
Urothelial papilloma.
Low grade papillary urothelial carcinoma.
Answer B.
Histological description
This lesion consists of urothelium which is normal in thickness thrown into papillary
folds. A few underlying nests are present representing their involvement of Von Brunn
nests or a tangential sectioning. Scattered nuclei are enlarged showing some variability
in size and shape. An accompanying ck20 stain showed full thickness positivity.
Discussion
This lesion has the overall growth pattern of papillary urothelial hyperplasia. The
distinction between papillary urothelial hyperplasia and a papillary neoplasm such as
papilloma or low grade papillary carcinoma is that in the latter there are well formed
distinct papillary fronds. In a papillary urothelial neoplasm the papillary formations are
complex with branching such that sectioning of the lesion results in the histological
appearance of fronds that appear to be dissociated from the underlying mucosa. In
contrast with papillary urothelial hyperplasia there are simple folds within the mucosa
such that sectioning does not give rise to a frond composed of a fibrovascular core
circumferentially surrounded by urothelium appearing to be “floating” separate from the
underlying mucosa. In a typical case of papillary urothelial hyperplasia there is a lack of
cytologic atypia. However in the current case there is pleomorphism warranting a
diagnosis of dysplasia yet not up to the level of carcinoma in-situ. The presence of full
thickness ck20 positivity supports the presence of dysplasia as opposed to reactive or
normal urothelium. Papillary urothelial hyperplasia in many cases represents a precursor
lesion to papillary urothelial neoplasms. The presence of dysplasia with early papillary
formation is even more worrisome for the heralding of subsequent papillary urothelial
neoplasms. If this is the first manifestation of urothelial disease in this patient, close
clinical follow up would be warranted.
Case 4
A 49 year old male was noted to a paratesticular mass. A frozen section was performed.
Choose the correct diagnosis
A. Adenomatoid tumor.
B. Metastatic adenocarcinoma.
C. Sertoli cell tumor.
D. Epithelioid hemangioendothelioma.
Answer A.
Histological description
Adjacent to the testis is a mass consisting of nests and cords of cells with abundant
eosinophilic cytoplasm. Many of the cells contain a clear cytoplasmic vacuole. The
nuclei are enlarged with prominent nucleoli. The background appears to be fibrotic.
Focally the lesion extends into the testis invading in between seminiferous tubules.
Elsewhere the lesion shows central infarction.
Discussion
One of the keys to recognizing this entity is its paratesticular as opposed to intratesticular
location. Relatively few entities involved the paratesticular region, with adenomatoid
tumor being one of the most common. Although these lesions may focally invade the
testis as seen in the current case, it is extremely rare for them to be totally intratesticular.
These lesions resemble epithelioid hemangioendothelioma in that they consist of cords or
nests of cells with vacuole formation. However no red blood cells are noted within the
vacuoles. An unusual but well recognized feature seen in the current case is the central
infarction. (Am J Surg Pathol 28; 77-83, 2004). Recognition of this lesion at the time of
frozen section may spare a patient orchiectomy as localized excision is adequate.
Diagnosis on permanent sections is more readily accomplished as one can perform
immunostains for calretnin demonstrating the lesion’s mesothelial origin. Although this
lesion is a mesothelioma, because adenomatoid tumor is a well described
clinicopathological entity and because the diagnosis of mesothelioma in this region has
the connotation of malignancy, these lesions are still noted as adenomatoid tumors rather
than mesotheliomas.
Case 5
A 20 year old male was noted to have a testicular mass and underwent orchiectomy.
Choose the correct diagnosis
A. Choriocarcinoma and teratoma.
B. Teratoma with prominent syncytiotrophoblastic giant cells.
C. Embryonal carcinoma.
Answer A.
Histological description
Some of the tumor is characterized by tubules lined by cuboidal epithelium as well as
epithelium with columnar cells showing subnuclear vacuoles. Elsewhere there are
areas of necrosis and hemorrhage surrounded by very pleomorphic cells. In areas a
dimorphic population may be recognized consisting of multinucleated cells with
abundant amphophilic cytoplasm and very pleomorphic nuclei adjacent to cells with
smaller yet still recognizably malignant nuclei with slightly grayer cytoplasm.
Discussion
This case is a nice example of choriocarcinoma in a malignant mixed germ cell
tumor. It is relatively rare to see choriocarcinoma as a component of a mixed germ
cell tumor. More frequently, one can see scattered syncytiotrophoblastic giant cells in
a setting of seminoma or less frequently embryonal carcinoma or teratoma. The
distinction between isolated syncytiotrophoblastic giant cells and choriocarcinoma is
the presence of cytotrophoblasts in choriocarcinoma. In cases with only isolated
syncytiotrophoblastic giant cells the giant cells tend to cluster around blood lakes and
dilated blood vessels further mimicking choriocarcinoma. However in
choriocarcinoma one tends to see not only tumor surrounding areas of hemorrhage
but areas of frank necrosis as well. Although pathologists tend to worry about
missing small foci of choriocarcinoma in a malignant mixed germ cell tumor, this is
not a critical issue in terms of treatment or prognosis. In a non seminomatous germ
cell tumor, the prognosis is based more on serum markers than on the histological
findings. This includes levels of alpha fetoprotein, HCG, and LDH. In addition
whether there are non-pulmonary visceral metastases is also of prognostic
significance. As it relates to trophoblastic cells, the presence of a HCG level less than
5000 IU/L is of good prognosis as compared to an intermediate prognosis with HCG
levels between 5000 and 50,000 and a poor prognosis with HCG levels greater than
50,000. Consequently, cases with scattered syncytiotrophoblastic giant cells or even
small foci of choriocarcinoma will typically have HCG levels of less than 5000 with a
good prognosis regardless whether there is choriocarcinoma present or absent. In
cases with a more significant choriocarcinoma component, there will be more
markedly elevated HCG levels in the serum with a correspondingly worse prognosis.
Case 6
A 55 year old male was noted to have a paratesticular lesion.
Choose the correct diagnosis
A.
B.
C.
D.
Leiyomyoma.
Adenomatoid tumor with smooth muscle hyperplasia.
Low grade leiyomyosarcoma.
High grade leiyomyosarcoma.
Answer C.
Histological description
The lesion consists of fasicles of spindle cells with abundant eosinophilic cytoplasm. The
nuclei are elongated and cigar shaped. Many of the nuclei appear relatively uniform
without significant pleomorphism. Other areas show more striking nuclear
pleomorphism. Mitotic figures are rare with no evidence of necrosis. The lesion is of
moderate cellularity.
Discussion
In an adult, the most common paratesticular soft tissue tumor is liposarcoma, typically
well differentiated. Paratesticular leiomyosarcomas are less frequently present.
Although adenomatoid tumors of the testis may show a very prominent smooth muscle
component one still will be able to identify the epithelial component of an adenomatoid
tumor which is lacking in the current case. Also the presence of atypia in the current case
rules out leiomyoma and smooth muscle hyperplasia with an adenomatoid tumor.
Although there is striking cytologic atypia, the overall cellularity is not high, mitotic
figures are not frequent, and the lesion lacks necrosis such that it would be best regarded
as low grade leiomyosarcoma. In a study from our institution, the key prognostic feature
is the grade of the tumor. All patients with low grade leiomyosarcomas were alive
without evidence of disease although a couple of patients experienced local recurrences.
In contrast all of the high grade leiomyosarcomas were dead of disease. Therapy
typically consists of radical orchiectomy. Immunohistochemically these lesions express
muscle markers as in other sites. The only pitfall that one must be aware of is as with
leiomyosarcomas elsewhere, some of these lesions may show focal expression for
cytokeratin.
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