College of American Pathologists

2013 — October Case of the Month

Posted October 24, 2013

CLINICAL SUMMARY: Testis/paratesticular  

CAP Foundation Online Case of the Month

Click Slide Image to View Case with DigitalScope

After reading the summary, try answering the three related multiple-choice questions below.

A 65-year-old man presented with a large right paratesticular mass. The mass, right testis and spermatic cord were resected. The mass was partially encapsulated with attached adipose tissue, weighed 416 g and measured 11.5 x 9.0 x 6.3 cm. The cut surfaces were tan-yellow and nodular with focal areas of fibrosis.

Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 35, and is a well-differentiated liposarcoma.

Criteria for Diagnosis and Comments:
Histologic sections of the tumor mass show an admixture of mature adipocytes and variable number of spindled cells in loose myxoid stroma. Bizarre stromal cells with marked nuclear atypia and varying numbers of multivacuolated lipoblasts are embedded in a fibrillary collagenous stroma. These histologic features are consistent with well-differentiated liposarcoma.

Well-differentiated liposarcoma (WDL), also referred to as atypical lipomatous tumor, is a locally aggressive malignant tumor accounting for 40-45% of all liposarcomas. These tumors occur in late adult life with peak incidence during the sixth and seventh decades. The most common site of involvement is deep soft tissue of the limbs, followed by the retroperitoneum and paratesticular area. WDL presents as a painless slowly enlarging mass that can attain a very large size before the patient seeks attention.

Histologically, WDL is composed of a mature adipocytic proliferation with variation in cell size. Focal adipocytic nuclear atypia, hyperchromatic and multinucleate stromal cells and lipoblasts in varying numbers are typical features. WDL has been traditionally subdivided into adipocytic (lipoma-like), sclerosing, inflammatory and spindle cell variants. These distinctions are largely arbitrary given that most tumors contain more than one pattern. However, certain patterns are more common in a given anatomic location: the inflammatory form occurs almost exclusively in the retroperitoneum while the sclerosing pattern is most often seen in retroperitoneal and paratesticular tumors. Occasionally, the stromal/fibrous component may form majority of the tumor with a limited lipogenic component posing a diagnostic challenge, particularly on small biopsies. A rare finding in WDL is the presence of heterologous differentiation in the form of smooth or striated muscle.

Although immunohistochemistry has limited value with adipocytic cells typically immunoreactive only for S-100 protein, cytogenetic features are more characteristic and helpful. Supernumerary (ring) and giant rod chromosomes containing amplification of 12q13-15 region, the site of several genes including MDM2 and CDK4, are characteristic of WDL cells. Fluorescence in-situ hybridization methods and more recently immunostaining to detect amplification of these genes have been shown to be of value in distinguishing WDL from various benign lipomatous lesions.

The histologic differential diagnosis of WDL includes lipoma and its variants which are generally smaller than WDL. Careful sampling and identifying adipocytic/stromal atypia and lipoblasts in the tumor in an appropriate clinical setting are most helpful in the diagnosis of WDL. Ancillary studies as described above can be crucial in confirming the diagnosis of WDL in some cases.

Areas of dedifferentiation resembling malignant fibrous histiocytoma (pleomorphic sarcoma) may occur in WDL. Adequate sampling for transition areas from WDL with lipoblasts to pleomorphic sarcoma is necessary to distinguish from malignant fibrous histiocytoma.

In the differential diagnosis of WDL in the paratesticular area, aggressive angiomyxoma and angiomyofibroblastoma-like tumor warrant consideration. Aggressive angiomyxoma typically occurs in the genital and pelvic regions of women of reproductive age and rarely occurs in the inguinal region, along the spermatic cord and in the scrotum of men. This neoplasm typically has infiltrating borders and shows scattered spindled and stellate shaped cells with thin and thick-walled blood vessels in a myxoid background. The spindled cells are generally positive for actins and desmin and consistently express both estrogen and progesterone receptors, but are negative for S-100.

Angiomyofibroblastoma-like tumor of male genital tract (cellular angiofibroma) is a distinct benign tumor occurring in the scrotum or inguinal region of older men. Histologically, these lesions are characterized by a cellular spindle cell component with bland cytologic features and stroma containing evenly dispersed small to medium-sized vessels with mural hyalinization. These tumors typically express CD34 and some are positive for smooth muscle actin and desmin.

WDL in superficial anatomic sites and amenable to surgery do not recur following complete excision. However, tumors in deep anatomic sites including spermatic cord areas tend to recur locally and also carry a higher risk of dedifferentiation.

Supplementary Questions:

Question Diagnostic Set
1. Which tumor is characterized by small to medium sized blood vessels with mural hyalinization? A. Aggressive angiomyxoma
B. Angiomyofibroblastoma-like tumor of male genital tract
C. Malignant fibrous histiocytoma (pleomorphic sarcoma)
D. Spindle cell lipoma
E. Well-differentiated liposarcoma
2. Which tumor can show areas of dedifferentiation to high grade sarcoma? A. Aggressive angiomyxoma
B. Angiomyofibroblastoma-like tumor of male genital tract
C. Malignant fibrous histiocytoma (pleomorphic sarcoma)
D. Spindle cell lipoma
E. Well-differentiated liposarcoma
3. Which tumor is most often characterized by MDM2 gene amplification? A. Aggressive angiomyxoma
B. Angiomyofibroblastoma-like tumor of male genital tract
C. Malignant fibrous histiocytoma (pleomorphic sarcoma)
D. Spindle cell lipoma
E. Well-differentiated liposarcoma

References

  1. Dei Tos and Pedeutour F. Atypical lipomatous tumour/Well differentiated liposarcoma. In: Pathology and genetics of soft tissue and bone tumours. WHO Classification of Tumors. IARC Press. Lyon. 2002:35-37.
  2. Weaver J, Downs-Kelly E, Goldblum JR, et al. Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms.Mod Pathol. Aug; 2008;21(8):943-949.
  3. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors, 5th Ed. Mosby. St. Louis. 2008.

Author:
2010
Vijaya B. Reddy, MD
Surgical Pathology Committee
Rush University Medical Center
Chicago, IL