The mystery’s last page: Granulation tissue or low grade sarcoma

Foreword :

The following write up shall shed light on the importance of getting a perfect diagnosis, taking a time honoured example which I have come to appreciate with time.?The impact of missing a diagnosis of cancer will be definitely be detrimental to the patient. Lesions that masquerade cancer loom large in everyday practice & pathologists use their time honed skills to keep the deception of such lesions at bay.

Morphology of certain entities can be strikingly similar, yet their nature poles apart, much alike an unhappy couple, the following example has nothing in common.

Granulation tissue or low grade sarcoma:

Granulation tissue is the quintessential reparative change which follows injury. Granulation tissue is simple by nature. It is composed of proliferating fibroblasts, young blood vessels & acute inflammation. Without granulation tissue healing cannot be effected. However on morphology (especially on cytology), the plump fibroblasts & ‘high endothelial venules’ of granulation tissue can simulate soft tissue tumours especially low grade sarcomas.

Low grade sarcomas are notorious lesions, difficult to diagnose when cellularity is low & pose specific problems. Low grade sarcomas such as inflammatory myofibroblastic tumour (the name itself suggests that the lesion has an inflammatory angle to it) & Kaposi sarcoma can have coexisting acute inflammation. Acute inflammation is almost always present in granulation tissue as WBC’s & the cytokine soup are an integral part of repair. It should also be remembered that, though rare, spindle cell carcinomas & spindle cell melanomas can also pose challenges while reporting.

Many a time clinicians interpret a discussion on this divide in morphology as incompetency in reporting. It should be emphasized that this farther the truth & the truth is seldom in black & white. A benign or inflammatory entity can be confused with a malignant lesion such as ?a low grade sarcoma.

Cues,Clues & Clamps

While differentiating between low grade sarcomas & granulation tissue could be difficult, there is definitely a way out of this eerie maze. That being said, the way out of the maze relies heavily on the advances in pathology. In the last decade the molecular mechanisms & mutations underpinning soft tissue tumours have been studied extensively. Immunohistochemistry profiles of soft tissue tumours have been well established, however new entities do crop up, once in a while. A couple of ?examples are given below :

1. Caldesmon differentiates smooth muscle tumours from myofibroblastic tumours.
2. Though nodular fasciitis is described as a self-limiting condition. The importance of a confirmatory diagnosis is being stressed. USP 6 (Ubiquitin specific protease)?gene rearrangement has added value to the traditional IHC panel of CD 34, SMA, Calponin, EMA & S100.

Learning curve:

While it is easy to preach from the pulpit that no stone should be left unturned in giving the lesion a ‘perfect’ diagnosis. Other factors such as availability of resources, competency & risk mitigation should be taken into account. It is always best not do any harm even if we aren’t able to do good. Hence it would be prudent to embrace the advances available rather than choosing to report on speculation. Such advances are indeed required in a handful of cases, to clamp down the miscreant.

The cover picture is from a 58 year old patient with a buttock lesion. The FNAC on microscopy showed plenty of blood vessels along with spindle cells, the occasional giant cell & abundant acute inflammation. The differential of low grade sarcoma & granulation tissue were considered. A biopsy & IHC were requested.