Teaching and Classes, Surg Path Conferences, 2004, SP Web 4-12-04
Case 1 Eighteen year-old male with large renal mass.
Diagnosis:
A. Metastatic Pulmonary Carcinoma
B. Clear Cell Sarcoma of the Kidney
C. Papillary Renal Cell Carcinoma
D. Renal Medullary Carcinoma
Answer: D, Renal Medullary Carcinoma
Histologic Description:
This is a highly aggressive tumor associated with extensive necrosis. The tumor features high
grade nuclei which are generally vesicular with prominent nucleoli. In some areas there is a
suggestion of hyaline intracytoplasmic inclusions, yielding a “rhabdoid” cytology. The tumor
has a cribriform and gland-forming architecture, and is associated with a desmoplastic reaction.
Extravasated amongst the tumor cells are red blood cells which are focally sickled. The
diagnosis was confirmed by hemoglobin electrophoresis, which revealed that the patient had
sickle cell trait.
Differential Diagnoses:
Metastatic carcinoma would be extremely unlikely in a patient at this age, but would be more of
a concern in an adult patient. Clear cell sarcoma of the kidney is also an aggressive neoplasm,
but would lack the gland formation and prominent nucleoli of this tumor. Papillary renal cell
carcinoma has a solid glandular variant, but lacks the high-grade cytology and desmoplastic
stroma associated with the current lesion.
Renal medullary carcinoma is a highly lethal cancer that almost exclusively strikes children and
young adults with sickle cell trait hemoglobinopathy. Some consider it to be a variant of
collecting duct carcinoma. Microscopically, the lesion has an invasive border and its
architecture ranges from reticular or yolk sac-like to gland forming. The cells frequently have
rhabdoid-type cytology, which raises the differential diagnosis of rhabdoid tumor of the kidney;
the latter though is almost exclusively a tumor of infants. Unfortunately, renal medullary
carcinoma is a highly lethal tumor with mean survival measured in weeks.
Ref: Am J Surg Path 1995; 19:1-11
Case 2 53 year-old female with 5 cm gastric mass.
Diagnosis:
A. Glomus Tumor
B. Paraganglioma
C. Carcinoid Tumor
D. Epithelioid Gastrointestinal Stromal Tumor
A. Glomus Tumor
Histologic Description:
The tumor is composed of nodules of rounded cells with a hyalinized and fibrotic stroma. Cells
have uniform round nuclei and well developed cytoplasm. The tumor cells label for smooth
muscle actin, and label for type 4 collagen in a pericellular pattern. CD117 and desmin were
negative.
Differential Diagnosis:
Paraganglioma would have a more vascularized stroma, and the nuclei would show more
“endocrine” features in the form of finely dispersed, “salt and pepper” type chromatin. Gastric
carcinoid tumors often arise is association with either atrophic gastritis or Zollinger-Ellison
syndrome. Solitary gastric carcinoids can be large like the current lesion. However, they also
should have more neuroendocrine type chromatin, and more trabecular patterns of growth.
Epithelioid gastrointestinal stromal tumor is a serious concern in this case, particularly given that
it is potentially treatable with gleevec. However, gastrointestinal stromal tumor (GIST) as
defined by c-kit immunoreactivity, and the current lesion was nonreactive for c-kit (CD117).
The stomach is in fact the most common site for glomus tumor within the gastrointestinal tract.
Glomus tumors are typically immunoreactive for actin, calponin, caldesmon, but negative for
desmin and c-kit. The tumor has overall a favorable prognosis, even though it is deep and must
be regarded as having uncertain malignant potential at the time of diagnosis.
Ref: Am J Surg Path 2002;16:301-311.
Case 3 40 year-old female with a 2 cm breast mass
Diagnosis:
A. Metaplastic Carcinoma
B. Fibromatosis
C. Fasciitis
D. Hypertrophic Scar
Answer: B, Fibromatosis
Histologic Description:
The tumor is composed of spindle cells with somewhat wavy nuclei separated by
abundant collagen. Blood vessels stand out in relation to the tumor cells and often appear to be
separated from them by a clear space. The tumor was completely nonreactive for all cytokeratins
(including CAM 5.2, AE1/AE3 and 34βE12), and demonstrated nuclear labeling for β-catenin.
This supports the diagnosis of fibromatosis.
Differential Diagnoses:
Metaplastic carcinomas may have a fibromatosis-like pattern; therefore, exclusion of
metaplastic carcinoma by utilization of multiple cytokeratin cocktails for immunohistochemistry,
(particularly those with high molecular-weight cytokeratins) is crucial. Fasciitis is extremely
rare within the breast, but is characterized by a more myxoid stroma and a tissue-culture-like
appearance of the fibroblastic cells. A hypertrophic scar would not show the orderly pattern of
growth of the current lesion, as well as the large size. Like deep fibromatoses, mammary
fibromatoses demonstrate activation of the Wnt/β-catenin pathway, which correlates with their
association with Familial Adenomatous Polyposis.
Ref: Hum Pathol 2002;22:39-46
Case 4 82 year-old male with a liver nodule discovered upon laparoscopy for a pancreatic
adenocarcinoma.
Diagnosis:
A. von Meyenberg Complex
B. Bile Duct Adenoma
C. Metastatic Pancreatic Adenocarcinoma
D. Reactive Bile Duct Proliferation in response to obstruction
B. Bile Duct Adenoma
Histologic Description:
The lesion is composed of proliferated ductules in a somewhat fibrotic stroma. Centrally,
the ductules have an elongated architecture. While intracytoplasmic mucin is evident, and there
is mild atypia, mitoses are not seen .
Differential Diagnoses:
Von Meyenberg complexes usually have a staghorn appearance and contain intraluminal
bile. Metastatic carcinoma should show more advanced cytologic atypia, and mitotic activity,
both of which are absent from the current lesion. Reactive bile duct proliferations are typically
associated with an edematous stroma and bile plugs, neither of which was present in the current
specimen.
Case 5 77 year-old female with an upper outer quadrant breast mass, status post-TAH/BSO two
years ago.
Diagnosis:
A.
B.
C.
D.
Papillary Carcinoma of the Breast, noninvasive
Metastatic Ovarian Carcinoma
Infiltrating Ductal Carcinoma
Malignant Melanoma
Answer: B Metastatic Ovarian Carcinoma
Histologic Description:
The tumor is associated with the lymphoid stroma, and likely is present within an axillary
lymph node. The tumor has a papillary architecture, and high grade cytology. Review of the
patient’s prior ovarian tumor revealed similar cytology. By immunohistochemistry, the tumor
was strongly immunoreactive for WT-1 in a nuclear fashion, and labeled for CA-125. GCDFP
but did not show definitive labeling of the tumor.
Differential Diagnoses:
In situ papillary carcinoma would be associated with myoepithelial cells, which were not present
in the current lesion. Lymphoid stroma would be most unusual for this lesion. This tumor has a
circumscribed border, which would make infiltrating ductal carcinoma unlikely. The staining for
the markers WT-1 and CA-125 support ovarian origin over breast. Melanoma is suggested by
the prominent nucleoli, but is excluded by the immunohistochemical labeling pattern.
Ovarian carcinoma is one of the more common tumors that metastasizes to the breast, along with
melanoma, lung carcinoma, gastric carcinoma, and renal cell carcinoma. Features that favor a
metastasis over primary breast carcinoma includes an absence of in situ component, a lack of
sclerosis or elastosis, a pushing border, and multiple satellite foci or lymphatic emboli.
Case 6 50 year-old female with 5 cm liver mass.
Diagnosis:
A.
B.
C.
D.
Hepatocellular Carcinoma
Leiomyosarcoma
Focal Fatty Change
Angiomyolipoma.
Answer: D, angiomyolipoma
Histologic Description:
The tumor is composed of plump epithelioid and spindled cells which show moderate
pleomorphism. Abnormal blood vessels with irregularly thickened walls and foci of fat are
associated with the spindled cells. The tumor was immunoreactive for HMB-45 and Melan-A,
and negative for HEPAR-1, supporting the diagnosis.
Differential Diagnoses:
Epithelioid angiomyolipomas of the liver are a great mimic of hepatocellular carcinoma,
particularly when they have a trabecular pattern and show pleomorphism.
Immunohistochemistry usually resolves this problem. Leiomyosarcoma can be mimicked by
angiomyolipomas with prominent smooth muscle differentiation. The vacuolated nature of the
smooth muscle cells in angiomyolipoma and the distinctive immunostaining pattern (positivity
for both actin and melanocytic markers) are also helpful. Focal fat accumulation in hepatocytes
can be mimicked by angiomyolipoma showing epithelioid cells and fatty differentiation.
Attention to the large size of the lesion should prompt reconsideration of the diagnosis, and
confirmatory immunohistochemistry.