Testis & paratestis

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Contributed by Melanie Bourgeau, M.D. and Debra L. Zynger, M.D.


Images hosted on other servers:

Contributed by Melanie Bourgeau, M.D.

Images hosted on other servers:

• Well differentiated liposarcoma
  • Supernumerary ring or giant marker chromosomes with material from 12q13-15 region (Genes Chromosomes Cancer 1999;24:30)
  • MDM2 amplification is main driver of tumorigenesis; other genes coamplified (CDK4, HMGA2) (Clin Cancer Res 2009;15:5696, Int J Cancer 2008;122:2233)
  • MDM2, CDK4 amplifications detected by FISH or real time PCR (Am J Surg Pathol 2007;31:1476)
• Dedifferentiated liposarcoma
  • Often gains additional cytogenetic alterations
  • More complex karyotype with high copy number variation but low rate of mutation (Oncotarget 2015;6:42429)
• Myxoid liposarcoma
  • Alterations involving 12q13 breakpoint, most commonly t(12;16)(q13;p11.2), resulting in FUS::DDIT3 fusion (95% of cases)
  • Rarely, t(12;22)(q13;q12.2) EWSR1::DDIT3 or more complex rearrangements (Oncogene 1996;12:489)
  • DDIT3 FISH is very sensitive and specific; rare false negatives for non-FUS::DDIT3 fusions (Genes Chromosomes Cancer 2023;62:167)
• Pleomorphic liposarcoma
  • Complex karyotype, with high intratumoral heterogeneity and copy number variations; similar to undifferentiated pleomorphic sarcoma and high grade myxofibrosarcoma (Diagnostics (Basel) 2021;11:430)

• Testicle, partial orchiectomy:
  • Well differentiated liposarcoma (4 cm) (see comment and synoptic report)
  • No evidence of dedifferentiation
  • Surgical margins are negative for tumor
  • Comment: Histologic sections demonstrate a well differentiated adipocytic tumor and fibrous septa containing atypical multinucleated stromal cells. Areas with sclerotic and inflammatory morphology are also seen. Immunohistochemistry for MDM2 is strongly positive in lesional cells, consistent with the above diagnosis.
• Note: if resection, the soft tissue synoptic template should be used in addition, with staging performed according to retroperitoneum

• Testicle, radical orchiectomy:
  • Dedifferentiated liposarcoma (10 cm) (see comment and synoptic report)
  • Well differentiated liposarcoma component is present
  • Surgical margins are negative for tumor
  • Comment: Histologic sections demonstrate a high grade nonlipogenic sarcoma with pleomorphic and spindle morphology, in association with a well differentiated adipocytic tumor. The dedifferentiated (nonlipogenic) component constitutes ~60% of the tumor. Immunohistochemistry for MDM2 is strongly positive in lesional cells, consistent with the above diagnosis.

• Testicle, partial orchiectomy:
  • Myxoid liposarcoma, low grade (3 cm) (see comment and synoptic report)
  • Surgical margins are negative for tumor
  • Comment: Histologic sections demonstrate a hypocellular myxoid lesion composed of small, bland, primitive mesenchymal cells and delicate, branching capillaries. There are occasional univacuolated and multivacuolated lipoblasts. No high grade features are identified. FISH is positive for DDIT3 rearrangement, confirming the above diagnosis.

• Testicle, radical orchiectomy:
  • Myxoid liposarcoma, high grade (5 cm) (see comment and synoptic report)
  • Surgical margins are negative for tumor
  • Comment: Histologic sections demonstrate characteristic features of a low grade myxoid liposarcoma as well as areas with high grade morphology, which constitutes ~30% of the tumor. FISH is positive for DDIT3 rearrangement, confirming the above diagnosis.

• Testicle, radical orchiectomy:
  • Pleomorphic liposarcoma (6 cm) (see comment and synoptic report)
  • Surgical margins are negative for tumor
  • Comment: Histologic sections demonstrate a high grade pleomorphic and spindle cell sarcoma with focal / extensive pleomorphic lipoblasts. FISH is negative for MDM2 amplification, consistent with the above diagnosis.

A 70 year old man is found to have an 11 cm cord lipoma during elective surgery for inguinal hernia repair. Representative histologic findings are shown in the image provided above. Which of the following tests would be most helpful in this context?

1. FISH for DDIT3 rearrangement
2. FISH for MDM2 amplification
3. Immunohistochemistry for HMGA2
4. Immunohistochemistry for MDM2
5. Immunohistochemistry for RB1

B. FISH for MDM2 amplification. The microscopic image demonstrates variably sized mature adipocytes and small areas of fibrous bands containing spindle cells without significant atypia. MDM2 FISH is recommended for deep / centrally located or large tumors (> 10 cm) with equivocal atypia, concerning clinical / imaging findings and recurrent tumors. Answer D is incorrect because MDM2 IHC has low sensitivity in distinguishing between lipoma and lipoma-like well differentiated liposarcoma (WDLPS). Answer C is incorrect because HMGA2 is positive in both lipomas and WDLPS. Answer E is incorrect because RB1 loss is seen in spindle cell / pleomorphic lipoma and atypical spindle cell pleomorphic lipomatous tumor (ASPLT) and is not a feature of conventional lipomas or WDLPS. Answer A is incorrect because although DDIT3 (12q13) may be amplified in some cases of WDLPS, DDIT3 rearrangements are characteristic of myxoid liposarcoma and do not occur in lipomas or WDLPS.

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Reference: Liposarcoma

A 75 year old man presents with worsening scrotal swelling. On exam, there is a grossly apparent, large, right inguinal mass with no skin changes or signs of infection. A computerized tomography (CT) scan reveals a right inguinal canal ovoidal soft tissue mass, measuring 6 cm in greatest dimension, that was not present on previous imaging performed 12 months prior for chronic back pain. No other abnormalities are noted. Clinical history is otherwise unremarkable. Representative histologic findings from the resected mass are shown in the provided image. Tumor cells are focally positive for desmin and STAT6. FISH is positive for MDM2 amplification. What is the most likely diagnosis?

1. Dedifferentiated liposarcoma
2. Leiomyosarcoma
3. Sarcomatoid carcinoma
4. Solitary fibrous tumor
5. Undifferentiated pleomorphic sarcoma

A. Dedifferentiated liposarcoma (DDLPS). The microscopic image demonstrates atypical spindled and multinucleated cells arranged in short fascicles. In this setting, DDLPS is the most likely diagnosis. Identification of a well differentiated liposarcoma (WDLPS) component is the most specific feature but is not identified in all cases. Answer B is incorrect because leiomyosarcomas do not have MDM2 amplification; in addition, they usually demonstrate more extensive staining for at least 2 myogenic markers. Focal staining for desmin is seen in DDLPS with and without myogenic differentiation. Answer D is incorrect because solitary fibrous tumors are characterized by NAB2::STAT6 fusions and do not have MDM2 amplifications. Focal staining for STAT6 may be related to the close proximity of the STAT6 gene (12q13) to the region amplified in WDLPS / DDLPS (12q13-15). Answer E is incorrect because undifferentiated pleomorphic sarcoma is a diagnosis of exclusion and therefore should be negative for MDM2 amplification. Answer C is incorrect because the lack of any significant clinical history or other imaging findings, together with the typical location and molecular alteration, makes DDLPS the most likely diagnosis in this case.

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Reference: Liposarcoma