Pulmonary Pathology Society

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January, 2025
Case of the Month

Clinical History:

A 27-year-old woman underwent surgical management of a suspected loculated pleural effusion discovered during evaluation for flank pain. At the time of surgery, a thick pleural rind was encountered with tenacious adhesions, dense exudate, and trapped lung.

H&E-stained sections of the pleural peel showed a variably cellular spindle cell neoplasm (Figure 1) comprising a relatively uniform population of atypical cells with centrally located oval shaped nuclei, inconspicuous nucleoli, and tapering bipolar eosinophilic cytoplasmic processes. Neoplastic spindle cells were predominantly arranged haphazardly within a pale staining basophilic myxoid stroma (Figure 2); however, focally, they were arranged in compact fascicles with collagenized stroma (Figure 3). Immunohistochemistry showed neoplastic cells were positive for calretinin (Figure 4) and SS18-SSX (Figure 5) with rare, isolated tumor cells staining for pancytokeratin cocktail (Figure 6); WT1 and claudin-4 were negative (not shown)

Q1. Which immunohistochemical stain is the most helpful in establishing the diagnosis?

SS18-SSX
Calretinin
Pancytokeratin
Claudin-4

Q2. The “classic” immunoprofile of mesothelioma is:

Calretinin and SS18-SSX positive; pancytokeratin, WT1, and claudin-4 negative.
Pancytokeratin, calretinin, and WT1 positive; claudin-4 and SS18-SSX negative.
Pancytokeratin and claudin-4 positive; calretinin, WT1, and SS18-SSX negative.
Pancytokeratin, calretinin, WT1, and SS18-SSX positive; claudin-4 negative.

Q3. The SS18-SSX fusion-specific antibody is:

Highly specific, but not sensitive for synovial sarcoma.
Not sensitive or specific for synovial sarcoma.
Highly sensitive and highly specific for sarcomatoid mesothelioma
Highly sensitive and highly specific for synovial sarcoma.

Answers to Quiz

Q1. A
Q2. B
Q3. D

Diagnosis

Monophasic synovial sarcoma

Discussion

The neoplastic spindle cell proliferation raised two main concerns, including monophasic synovial sarcoma and sarcomatoid mesothelioma. The monotony of the spindle cell proliferation with focal compact arrangement was typical of synovial sarcoma. However, while focal myxoid change is a relatively common finding in synovial sarcomas, it is rarely a predominant finding as it was in this case. Prominent myxoid stroma is also known to occur in mesothelioma, but has been reported almost exclusively in epithelioid mesotheliomas. The presentation as diffuse pleural disease complicates this case, since this presentation is characteristic of diffuse pleural mesothelioma and although thorax synovial sarcomas are well documented, they tend to present as localized lesions.

Mesotheliomas are characterized by positive staining for pancytokeratin, calretinin, and WT1 by immunohistochemistry, but sarcomatoid meostheliomas may lose some of these markers and the negative WT1 did not exclude this diagnostic consideration. Frustratingly, synovial sarcomas also typically express keratins with over half of cases showing immunoreactivity for calretinin that is diffuse in up to one-third of cases. Indeed, had a diagnosis of synovial sarcoma not been considered in the differential diagnosis, this patient may have been labeled as having sarcomatoid mesothelioma. In this regard, immunoreactivity for the SS18-SSX fusion protein was particularly helpful in avoiding this diagnostic misstep.

Synovial sarcoma is characterized by chromosomal translocation t(X;18)(p11;q11), resulting in the fusion of SS18 (formerly SYT) with one of three highly homologous SSX genes. Immunohistochemistry for the fusion-specific SS18-SSX antibody is highly sensitive and specific for the diagnosis of synovial sarcoma. To date, SS18-SSX fusion has not been reported in mesothelioma; therefore, this feature is helpful in differentiating between these entities particularly when faced with ambiguous immunohistochemistry

Take home message for trainees: Immunohistochemistry for SS18-SSX is a useful diagnostic tool to distinguish between sarcomatoid mesothelioma and monophasic synovial sarcoma

References

Baranov E, McBride MJ, Bellizzi AM, et al. A novel SS18-SSX fusion-specific antibody for the diagnosis of synovial sarcoma. Am J Surg Pathol 2020;44:922-33.

Klebe S, Prabhakaran S, Hocking A, et al. Pleural malignant mesothelioma versus pleuropulmonary synovial sarcoma: a clinicopathological study of 22 cases with molecular analysis and survival data. Pathology 2018;50:629-34.

Krane JF, Bertoni F, Fletcher CD. Myxoid synovial sarcoma: an underappreciated morphologic subset. Mod Pathol 1999;12:456-62.

Weinbreck N, Vignaud JM, Begueret H, et al. SYT-SSX fusion is absent in sarcomatoid mesothelioma allowing its distinction from synovial sarcoma of the pleura. Mod Pathol 2007;20:617-21.

Contributors