My diagnosis: Leiomyosarcoma

I have to admit that I reached this diagnosis only after I viewed the IHC photos provided by the original hospital.

Here is how I “analyzed” this case (underscore indicates the key description words). Firstly, the patient is a 52 years old male, and the tumor is located in the submucosal of nasal cavity.  It is a hypercellular spindle cell tumor, even though it is also highly pleomorphic in many areas. The tumor cells form long fascicles intersecting with each other in better differentiated areas (best viewed in photo 9), while this feature is not that obvious in highly pleomorphic areas.  The distinct high power feature is abundant thick eosinophilic cytoplasm of the tumor cells, with active mitosis, including atypical mitosis. No significant inflammation (the focal scattered eosinophils might be related to the nasal location of the tumor), myxoid change or tumor necrosis identified. Importantly, as pointed out by many participants, the respiratory mucosa seems intact, with no squamous metaplasia or squamous cell carcinoma in situ identified. At this point, my differential diagnosis will be: 1. Sarcomatous (spindle cell) squamous cell carcinoma, which is not uncommon, especially in the head and neck area; 2. leiomyosarcoma, which is very uncommon for this location; 3. melanoma, which can be spindly and amelanotic. The IHC photos showed that the tumor cells are positive for SMA (diffuse, not “tram track” like) and vimentin, negative for cytokeratin, s-100, desmin and myoglobin. As the SMA is convincingly positive and other markers are negative, the diagnosis of leiomyosarcoma is unavoidable.

A few comments about the immunohistochemistry in this situation: 1. I would apply a few more cytokeratin markers, such as high molecular weight cytokeratin and p63, and perform the stain on couple of blokes, for tumors like this, to avoid missing those focally cytokeratin positive sarcomatous carcinomas. 2. Leiomyosarcoma can be positive for cytokeratin (up to 40%, called anomalous expression), but is more often with CK8 and CK18, and with dot like pattern. It can also be focally s-100 positive. Fortunately, that is not the case here. Otherwise it could cause more confusion.  3. Desmin and caldesmon are smooth muscle markers, but their positivity is variable in leiomyosarcomas in different locations.

Please forgive me for not being able to discuss in detail on the other differential diagnoses listed by many participants. Briefly: Inflammatory myofibroblastic tumor will at least have more inflammation and myxoid changes; MPNST will have slender, wavy spindle cells with asymmetrical nuclei, and focal s-100 positivity; Rhabdomyosarcoma embryonal type (apparently this is not the alveolar type) should have the classical strap and racquet-shaped cells with cross striations, at least focally. Plus, the tumor is SMA (usually negative in skeletal muscle) positive, but desmin (sensitive for skeletal muscle, even in poorly differentiated rhabdomyosarcomas) and myoglobin negative (of course, it is better to use myogenin here); Pleomorphic sarcoma is a diagnosis of exclusion; The marked pleomorphism and active mitosis, especially the atypical mitosis will exclude the possibility of any benign/reactive process.

To my opinion, XHYong could be the price winner. His/Her differential diagnoses are more focused, and on the right track.