Clinical history: 43 y.o. white female patient with a 4 years history of infiltaring
poorly differented ductal carcinoma of the breast presenting with a pelvic mass.
The sections were taken from the pelvic tumor. An immunostain for GCDFP is
negative.
Choose a correct diagnosis:
a. Metastatic ductal carcinoma of the breast
b. High grade serous carcinoma
c. Granulosa cell tumor
d. Metastatic melanoma
Correct diagnosis: High grade serous carcinoma
Discussion:
The mass consists of sheets of poorly differentiated tumor cells with scattered
gland formation that is histologically different from the patient's ductal carcinoma
of the breast (see image). The tumor is diffusely and strongly positive for CK7,
ER, PAX-8 and WT-1, variably positive for PR and is negative for GCDFP, CK20,
CEA, MelanA, SMA, Desmin, CD34 and S100. This immunoprofile supports an
ovarian origin and is consistent with a high grade serous carcinoma.
The origin of metastatic poorly differentiated carcinomas of the breast and ovary
can be difficult to recognize. This is particularly true if the metastasis occurs in
an anatomic location where both tumors commonly metastasize. Rarely, ovarian
tumor s can metastasize to the breast or axillary lymph nodes where they may be
misdiagnosed as mammary carcinoma. Similarly, a subset of breast cancer
(typically lobular carcinoma) can involve the ovaries and thus present as pelvic
masses. Immunohistochemistry is helpful in most instances, since breast
cancers are PAX-8 and WT-1(with rare exceptions for WT-1) negative, whereas
ovarian serous carcinomas are positive. The opposite is true our most used
breast markers GCDFP and mammoglobin. While the majority of ovarian tumors
are negative for both markers, there are tumors that are positive for either or both
markers.
Clinical history: 66 y.o. white male patient with a 14.5 cm mediastinal mass
that was attached to the pulmonary ligament.
Choose a correct diagnosis:
a. Solitary fibrous tumor
b. Leiomyoma
c. Leiomysarcoma, low grade
d. Desmoplastic mesothelioma
Correct diagnosis: Leiomysarcoma, low grade
Discussion:
NOTE: The tumor infiltrates and distends the pleura and focally involves the
serosal surface, however, the attached portions of lung do not show invasion into
the lung parenchyma. The tumor is variably cellular ranging from highly cellular
areas with storiform pattern to hyalinized areas with low cellularity. Pleomorphic
tumor cells are present but no necrosis is noted and mitosis are not readily
identified. Immunostains demonstrate that the tumor cells are desmin, smooth
muscle actin and bcl-2 positive, and cytokeratin (AE1/AE3), S-100 and CD34
negative. This staining pattern supports the diagnosis of a smooth muscle
neoplasm. Focal dystrophic ossification is also seen. The tumor focally
infiltrates fibroadipose tissue consistent with parietal pleura where tumor is seen
abutting but not involving the inked surface of fibroadipose tissue. These areas
may represent the site of attachment to the parietal pleura observed during
surgery.
On H&E stain the tumor is a low grade spindle cell neoplasm with features of a
low grade smooth muscle cell tumor. The characteristic vessels of a solitary
fibrous tumor are not present. Immunohistochemically, the tumor cells express
muscle markers, and are negative for cytokeratin, CD34 and S-100 a pattern that
supports. Bcl-2 positivity is usually not seen in smooth muscle cell tumors and is
interpreted as aberrant expression. Since this a pleural/mediastinum based
smooth muscle neoplasm it should be graded as a deep seated smooth muscle
tumor. Because of the presence of pleomorphic tumor cells even in the absence
of necrosis and increased mitotic activity the tumor should be considered a low
grade leiomyosarcoma.
Clinical history: 67 y.o. white female patient with 14 cm left kidney mass.
Choose a correct diagnosis:
a. Mixed epithelial and stromal tumor of kidney
b. Cystic nephroma
c. Cystic renal cell carcinoma
d. Polycystic kidney disease
Correct diagnosis: Mixed epithelial and stromal tumor of kidney
Discussion:
The tumor exhibits morphologic features of both cystic nehproma and mixed
epithelial and stromal tumor (MEST) of the kidney. It contains a dominant (12.5
cm) cyst that has no lining and is filled with hemorrhagic acellular material. The
surrounding smaller cysts are lined by a single layer of flat epithelial or hobnail
cells. The intervening stroma is fibrotic with focal areas showing hypercellular,
ovarian-type stroma. Scattered aggregates of smaller tubular structures with
surrounding cellular stroma are also present. Areas with multiple, small to
medium sized cysts and scant fibrotic intervening stroma represent features
typically seen in cystic nephroma, whereas areas with more abundant stroma
with focal small tubular structures are more often seen in MEST. The
morphologic features of these two rare benign neoplasms show significant
overlap and thus in selected cases the distinction between these two entities
can be difficult.
Reference: Am J Surg Pathol, vol 31;No4:489-500; Apr. 2007.
Clinical history: 28 y.o. white male patient with 3.2 cm subcutaneous soft
tissue mass on the back
Choose a correct diagnosis:
a. High grade sarcoma consistent with malignant fibrous histiocytoma
b. Malignant melanoma
c. Malignant peripheral nerve sheath tumor
d. Pleomorphic rhabdomyosarcoma
Correct diagnosis: Pleomorphic rhabdomyosarcoma
Discussion: The tumor is composed of variably pleomoprpic spindle and
focally polygonal shaped cells with variable amount of dense eosinophilic
cytoplasm. The mitotic activity is high and no necrosis is noted in the single
section available for review. Immunostains demonstrate that the tumor cells are
positive for desmin and smooth muscle actin, focally positive for myogenin and
cytokeratin (AE1/AE3 and Cam5.2), and are negative for CK903, S-100 and
Melan-A. This staining pattern supports the diagnosis.
Pleomorphic rhabdomyosarcoma (PRMS) is a high grade sarcoma composed of
polygonal, round and spindle shaped cells with dense eosinophilic cytoplasm
marked pleomorphism that lack morphologic evidence of myogenic
differentiation. No embryonal or alveolar component should be noted. PRMS
occurs in adults (more commonly in males) and most are in deep soft tissues of
the extremities. Cross striations are extremely rare. Clinically, they are rapidly
growing painful lesions. Like other muscle tumors PRMS express common
muscle markers like desmin, skeletal muscle myosin, variably express smooth
muscle actin and myogenin and MyoD1. The MyoD1 and myogenin expression
is usually more limited than those seen other types of RMS. Epithelial markers
and S-100 are usually negative. The prognosis is poor.
Clinical history: 28 y.o. woman with an anal fistula
Choose a correct diagnosis:
a. Pilonidal sinus
b. Pulse granuloma
c. Granuloma annulare
d. Crohn’s disease
Correct diagnosis:
Pulse granuloma
Discussion: Sections show anal skin with dermal fibrosis, fistula tract and small
hyalinized fibrotic perivascular nodules with associated mild chronic inflammation
skin with fistula tract and associated (so called hyaline angiopathy or pulse
granuloma).
Hyaline angiopathy or pluse granuloma are hyalinized ring-like or nodular
structures that are seen in areas of chronic inflammation. In the oral cavity they
typically occur in areas of periostitis often with associates food particles. The
finding has no clinical significance and is thought to be secondary to a reaction to
seeds and other food vegetable matter. An alternative hypothesis is that they
represent old vasculitis.
Clinical history: 42 y.o. African American female patient with a right lower lobe
lung nodule.
Choose a correct diagnosis:
a. Organizing pneumocystis pneumonia
b. Organizing Cryptococcus pneumonia
c. Sarcoidosis
d. Histoplasmosis
Correct diagnosis:
Organizing Cryptococcus pneumonia
Discussion: Sections show a lung nodule with organizing frothy exudate with
associated chronic inflammation with small poorly formed granulomata and
scattered giant cells. The nodule is well demarcated but not encapsulated and
does not have a fibrous wall. No necrosis or hyalinization is present. On H&E
stains there are small refractive appearing round structures within the frothy
exudates and in the cytoplasm of some giant cells that are positive for variably
sized round to oval spore forms on a fungal (GMS) stain. No dot-like staining is
noted within the organisms. A mucin stain is negative, whereas a FontanaMasson stain shows strong staining in the wall of these microorganisms
consistent with capsule deficient cryptococci. Rarely, organizing, vaguely
granulomatous inflammation may be seen in association with both pneumocystis
and cryptococcus infections and thus can be difficult to diagnose. In the majority
of cases Cryptococcus can be diagnosed by performing a mucin stain which can
highlight the mucopolysaccharide capsule of the organisms. In a minority of
cases, like the current one, however, the capsule is lost and therefore a mucin
stain is negative. Based on the staining pattern on a fungal stain the
differentiation between Cryptococcus and other fungal organisms can be difficult.
A Fontana-Masson stain is very useful in this setting since it will only stain
capsule deficient cryptococci.