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:

  1. Ependymoma
  2. Pylocytic astrocytoma
  3. Subependymoma
  4. 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 fossawhere 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 hemosiderindeposits. 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:

  1. Oncocytoma
  2. Renal cell carcinoma, chromophobe type
  3. Renal cell carcinoma, conventional type
  4. 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:

  1. Fibromatosis
  2. Myofibroblastoma
  3. Carcinosarcoma
  4. 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):249-60

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 #6Angiomyolipoma

Clinical History: 65-year-female with a flank mass.

Choose the correct diagnosis:

  1. Angiomyolipoma
  2. Normal peri-renal adipose tissue
  3. 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.