Subependymoma
Nephrogenic adenoma
Renal cell carcinoma, Chromophobe type
Leiomyoma, kidney
Myofiboblastoma, breast
Angiomyolipoma
CASE 1: Case #1: Subependymoma
Clinical History: 48-year-old man with a brain mass.
Choose the correct diagnosis:
A.
B.
C.
D.
Ependymoma
Pylocytic astrocytoma
Subependymoma
Subependymal giant cell astrocytoma
Histology: The tumor is highly fibrillary, with areas of clustering of the nuclei. The
nuclei show uniform, delicate chromatin and a lack of perinuclear cytoplasm.
Calcifications and microcyst formation can be seen.
Discussion: Subependymomas show characteristic clustering of nuclei and highly
fibrillated cell processes, along with microcysts, which readily distinguish it from other
gliomas. The subependymal giant cell astrocytoma of tubular sclerosis is a cellular
spindle and epithelioid lesion with cells showing eosinophilic cytoplasm and vesicular
nuclei with prominent nucleoli. All of these features are not seen in subependymomas.
Ependymomas may show overlap in architecture with subependymomas. Unlike the
ependymoma, subependymoma is less cellular and usually seen in adults.
Subependymomas are slow growing lesions that arise in the wall of the ventricles in the
brain, or rarely, in the spinal cord. Usually these lesions are found incidentally, however,
they become symptomatic when they occur in the posterior fossa where they can
compress brain stem or cranial nerves. The tumor is composed of ependymal and
astrocyte-like cells. Subependymomas that occur in the lateral ventricles tend to show
prominent micro-cystic changes. Nuclear pleomorphism and occasion mitoses can be
seen in these tumors. Larger lesions will often show hemosiderin deposits.
Subependymomas of the fourth ventricle usually show less microcystic change, are more
fibrillar, and the cells often appear more uniform than those occurring in the lateral
ventricles. Subependymomas are immunoreactive for S100 and GFAP. These tumors
are one of the few gliomas considered biologically benign.
CASE 2: Nephrogenic adenoma
Clinical History: 64 year old male with hematuria
Choose the correct diagnosis:
1. Adenocarcinoma of the prostate
2. High grade papillary urothelial carcinoma with lamina propria invasion
3. Nephrogenic adenoma
4. Clear cell adenocarcinoma
Histology: The bladder biopsy shows a lesion with papillary projections lined by a
single layer of cuboidal cells with hobnailing. Tubules with the same type of cuboidal
cells are seen in the lamina propria, some of these structures resemble vessels. Signet
ring cell-like tubules are also seen. Occasional hyalin peritubular sheaths are seen. The
lesion lacks mitoses.
Discussion: Nephrogenic adenoma or metaplasia consists of cuboidal cells with
hobnailing arranged in tubules, structures resembling vessels, cords and individual cells,
papillary configurations, and signet ring cell-like tubules. Sometimes thyroidization of
the tubules, and hyalin peritubular sheaths may be seen. Nucleoli may be prominent, but
mitoses are usually not seen. Urothelium overlying nephrogenic adenoma often shows
cuboidal metaplasia.
The tubular structures of nephrogenic adenomas may be confused with prostatic
adenocarinoma, and the hobnail cells resemble those seen in clear cell (mesonephic)
adenocarcinoma. Nephrogenic adenomas are cytokeratin positive. Focal prostate specific
antigen and PSAP positivity may be seen in nephrogenic adenoma cases, and therefore,
cannot reliably distinguish it from prostate cancer. Nephrogenic adenoma can mimic
prostate cancer because of: the presence of tubules, cords, and signet ring-like tubules;
prominent nucleoli; muscle involvement; blue-tinged mucinous secretions; focal prostate
specific antigen and PSAP positivity; and negative staining in some cases for high
molecular weight cytokeratin (34betaE12). Features useful in the diagnosis of
nephrogenic adenoma include the following: distinctive nephrogenic patterns, such as
papillary and "vascular," cuboidal metaplasia in the adjacent urothelium, thyroidization,
hyalin peritubular sheaths, associated inflammation, and lack of mitoses.
Nephrogenic adenoma or metaplasia are considered to be a benign metaplastic process.
Some form of previous bladder insult or surgery, including recurrent urine infections,
urinary stones, urinary tract instrumentation, placement of ureteric stents, intravesical
therapy and open bladder surgery, is often revealed in the patient's history.
REFERENCES:
Allan CH, Epstein JI. Nephrogenic adenoma of the prostatic urethra: a mimicker of
prostate adenocarcinoma. Am J Surg Pathol. 2001 Jun;25(6):802-8.
Tse V, Khadra M, Eisinger D, Mitterdorfer A, Boulas J, Rogers J. Nephrogenic adenoma
of the bladder in renal transplant and non-renal transplant patients: a review of 22 cases.
Urology. 1997 Nov;50(5):690-6.
CASE 3: Renal cell carcinoma, chromophobe type
Clinical History: 65-year-old female with a renal mass.
Choose the correct diagnosis:
A.
B.
C.
D.
Oncocytoma
Renal cell carcinoma, chromophobe type
Renal cell carcinoma, conventional type
Granular cell carcinoma
Histology: The lesion consists of a solid sheet of cells. Some of the cells have a pale
appearance with abundant pale, lightly eosinophilic granular cytoplasm. Other cells are
more eosinophilic in appearance. All of the cells show prominent cell borders. The
nuclei show variation in size and shape, some being small and round while others are
large and irregular. Binucleated cells are commonly seen. Perinuclear halos are easily
identified throughout the tumor.
Discussion: 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 this case. Also, oncocytomas show uniformly round nuclei without
nuclear irregularity or pleomorphism, which is seen in this case. The nuclei would also
lack perinuclear halos in contrast to a chromophobe renal cell carcinoma. In addition,
oncocytomas do not have such distinct cell borders as a chromophobe renal cell
carcinoma. The Hale’s colloidal iron stain, which stains for acidic mucin, would be
helpful in cases where it is difficult to tell the two lesions apart. A chromophobe renal
cell carcinoma should 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 Hale’s colloidal iron. In contrast to the conventional or
clear cell type of renal cell carcinoma, chromophobe renal cell carcinomas do not show
optically clear cytoplasm, but rather have a fine granular and lightly eosinophilic
appearance. The term granular renal cell carcinoma is no longer used. Tumor cells with
a granular appearance may be seen in any number of renal cell carcinoma subtypes
including conventional type renal cell carcinoma, papillary renal cell carcinoma, and
chromophobe type renal cell carcinoma.
CASE 4: Leiomyoma
Clinical History: 44-year-old female with a renal mass.
Choose the correct diagnosis:
1. Leiomyosarcoma
2. Leiomyoma
3. Sarcomatoid renal cell carcinoma
Histology: The tumor is well circumscribed. The cellular tumor consists of plump
spindle cells arranged in short bundles or interlacing fascicles. In some areas, the spindle
cells form long sweeping fascicles. Mitotic figures are absent.
Discussion: Renal leiomyoma is a rare tumor that typically occurs in the renal capsule.
The spindle cell proliferation raises the possibility of a sarcoma, however sarcomas show
greater mitotic activity and/or necrosis, which are not seen in the current lesion.
Sarcomatoid renal cell carcinoma would show more cytologic atypia, and an infiltrative
pattern. Immunostains for cytokeratin, actin and HMB-45 would be helpful, as
sarcomatoid renal cell carcinomas would show patchy cytokeratin staining and would be
negative for actin and HMB-45. It has been reported that some renal leiomyomas label
with HMB-45 and may be a variant of angiomyolipoma with a predominance of the
smooth muscle component.
REFERENCE:
Nikaido T, Nakano M, Kato M, Suzuki M, Ishikura H, Aizawa S. Characterization of
smooth muscle components in renal angiomyolipomas: Histological and
immunohistochemical comparison with renal capsular leiomyomas. Pathol Int. 2004
Jan;54(1):1-9.
CASE 5: Myofibroblastoma
Clinical History: 65 year-old male with a breast mass.
Choose the correct diagnosis:
A.
B.
C.
D.
Fibromatosis
Myofibroblastoma
Carcinosarcoma
Leiomyosarcoma
Histology: The tumor is composed of plump spindle cells with somewhat purplish
cytoplasm and nuclei with vesicular chromatin and punctate but prominent nucleoli.
Mitoses are not seen. The stroma contains thickened collagen bundles.
Discussion: The spindle cell proliferation raises the possibility of a sarcoma, however
sarcomas show greater mitotic activity and/or necrosis, which are not seen in the current
lesion. Metaplastic carcinoma would show more cytologic atypia. Immunostains for
cytokeratin and CD 34 would be helpful, as metaplastic carcinomas would show patchy
cytokeratin staining and would be negative for CD34. A fibromatosis would feature
more prominent thin-walled blood vessels and greater collagen deposition. In contrast to
myofibroblatoma, fibromatosis typically does not label for CD34.
Myofibroblastoma was first described in the male breast, and is more common in males
than females. This spindle cell neoplasm with ill-defined cytoplasm and somewhat
tapered nuclei shows prominent dense, ropy collagen. The tumor labels with CD34 and
Some lesions may label with desmin. These lesions typically show no mitotic activity,
and are clinically benign. It has been proposed in the literature that this lesion is related
other benign spindle cell lesions in the breast that arise from the mammary stromal cell.
REFERENCES:
1) Magro G, Bisceglia M, Michal M, Eusebi V. Spindle cell lipoma-like tumor, solitary
fibrous tumor and myofibroblastoma of the breast: a clinico-pathological analysis of 13
cases in favor of a unifying histogenetic concept. Virchows Arch. 2002 Mar;440(3):24960
2) Pauwels P, Sciot R, Croiset F, Rutten H, Van den Berghe H, Dal Cin P.
Myofibroblastoma of the breast: genetic link with spindle cell lipoma. J Pathol. 2000
Jul;191(3):282-5.
CASE 6: Case #6
Angiomyolipoma
Clinical History: 65-year-female with a flank mass.
Choose the correct diagnosis:
A.
B.
C.
Angiomyolipoma
Normal peri-renal adipose tissue
Liposarcoma
Histology: The tissue consists predominantly of adipose tissue. The adipose tissue lacks
atypia or lipoblasts. Focally, clusters of spindle cells with eosinophilic cytoplasm can be
identified, consistent with a smooth muscle component. Rare abnormal thick walled
vessels can be seen.
Discussion: A typical angiomyolipoma consists of three components, which include
thick wall vessels, smooth muscle cells and adipose tissue. However, variation in the
proportion of the components may be seen in various tumors. In this case the adipose
tissue predominates. As the adipose tissue in this case lacks atypia or lipoblasts and
shows focal clusters of eosinophilic smooth muscle cells, liposarcoma and normal
adipose tissue are unlikely. Immunohistochemical stains are helpful in differentiating
these lesions. Angiomyolipoma is intensely positive upon immunostaining with HMB45.
20% to 50% of angiomyolipomas are seen in association with patients who have tuberous
sclerosis. Angiomyolipomas may present in multiple locations, including lymph nodes,
which is thought to represent multi-focal disease rather than metastasis. The majority of
angiomyolipomas are benign lesions and do not metastasize. However, there are rare
reported cases of angiomyolipomas with malignant behavior, usually with an epithelioid
morphology. In cases of epithelioid angiomyolipomas, the issue should be raised to the
clinician that, although many cases with similar histology have not behaved aggressively,
this histology may rarely be associated with aggressive behavior.
References:
L’hostis H, Deminiere C, Ferriere JM, Coindre JM. Renal angiomyolipoma: a clinical
pathologic immunohistochemical and follow-up study of 46 cases. Amer Jnl Surg Path;
1999; 23: 1011-1020.