Neck, Soft Tissue

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2021, Case 20, and is calcifying fibrous tumor in soft tissue.

The information provided in this case was accurate and correct at the time of publication in 2021.

Any changes in terminology since the time of publication may not be reflected in this case.

​​​​Calcifying fibrous tumor (CFT) is a rare tumor with a distinctive histological presentation. The slide shows a densely fibrous lesion with abundant dystrophic and psammomatous calcifications composed of scattered bland spindle cells. Chronic inflammatory cells including plasma cells are present. Initially referred to as childhood fibrous tumor with psammoma bodies, the name calcifying fibrous pseudotumor was proposed in 1993 as additional cases revealed less of a predilection for children. The ​​​​2013 World Health Organization (WHO) classification used the term “calcifying fibrous tumor,” with “tumor” chosen to relay the rare but potential risk of recurrence.​

CFT was originally described as a subcutaneous soft tissue entity but has since been reported in a wide variety of locations, including the gastrointestinal tract (most common), pleura, abdominal cavity, and neck. CFT have a mean diameter 4 cm (range 0.1 to 25 cm) and are found incidentally on physical exam, but tumor growth may cause patients to present with mass effect or other site-specific symptoms. Most CFT are solitary lesions; however, there have been reports of multifocal tumors in up to 10% of cases and a case of 2 siblings with multiple CFT. This has led to speculation on a potential genetic susceptibility or environmental cause. The median age at time of diagnosis is 33.6, years with CFT being identified across all age ranges. Additionally, depending on the study, CFT either do not appear to show a gender predilection or demonstrate a slight female predominance. CFT are benign and appropriately treated with local resection. The risk of recurrence is small, and there have been no reported deaths.

Histologically, CFT are usually well-circumscribed but unencapsulated, paucicellular lesions composed of hyalinized fibrous tissue and variable numbers of both psammomatous and dystrophic calcifications distributed throughout the lesion. Associated chronic lymphoplasmacytic inflammation is a consistent finding. Adjacent normal structures such as adipose tissue and neurovascular bundles can become trapped in the lesion. CFT in the gastrointestinal tract differ from their soft tissue counterparts based on prominent lymphoid cuffs and increased perivascular lymphocytes relative to the soft tissue cases. Lesional cells have been found to express Factor XIIIa and vimentin but lack staining for actin, desmin, S100, and cytokeratins. There have been inconsistent results with regards to CD34 expression, and the current understanding is that CD34 is variably immunoreactive in CFT.

Imaging studies of CFT reflect their histological composition well, characteristically revealing a well-circumscribed mass containing scattered calcifications. CT and MRI are essential in surgical planning. CT is better at detecting areas with early mineralization that may be missed on other imaging modalities and can demonstrate the clear line of delineation between the mass and the adjacent tissues characteristic of CFT.

Some cases of CFT have shown an ​​increased IgG4:IgG ratio in the plasma cell population, and a potential association between immunoglobulin G4-related disease (IgG4-RD) and CFT has been postulated. IgG4-RD is a fibroinflammatory disease with a dense lymphoplasmacytic infiltrate, IgG4-positive plasma cells, and elevated serum IgG4. However, not all cases of CFT have shown an ​​increased IgG4:IgG ratio in the plasma cells, and serum IgG levels are not always available for comparison. Further studies are required to deduce the relationship between IgG4-RD and CFT.

Calcifying aponeurotic fibroma (CAF) is a pediatric entity with a predilection for the distal extremities, notably the hands and feet. It is a biphasic fibroblastic neoplasm with spindled fibroblasts and fibrocartilaginous nodules. While a benign entity, CAF tends to be less well circumscribed than CFT and has a higher local recurrence rate. Cartilage and location are the best ways to distinguish this entity from CFT.

Desmoid fibromatosis is a soft tissue tumor with a high rate of local recurrence. It is usually located in deep soft tissues. It is characterized by a proliferation of uniform spindle cells in elongated fascicles with a collagenous stroma. Unlike CFT, it typically lacks calcifications and stains positively for B-catenin (nuclear) by immunohistochemistry.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor often seen in children and young adults. It had been previously theorized that CFT represented a late stage of IMT or occurred in association with IMT. Currently, the WHO classifies CFT as a distinct entity, and there are histologic and immunophenotypic differences from IMT. While IMT also histologically presents as a spindle cell proliferation with a prominent lymphoplasmacytic infiltrate, they are generally more cellular and they rarely have calcifications. Up to 50% of IMT also have an ALK rearrangement, which is not seen in CFT.

Nodular fasciitis is a proliferation of fibroblasts and myofibroblastic cells. It is benign and self-limited but can be a mimicker of sarcomas due to its fast growth, high cellularity, and increased mitotic activity. Histologically, it presents with spindled cells, elongated nuclei, mitotic activity, extravasated red blood cells, inflammatory cells, and focal myxoid areas. Calcifications are not described. Smooth muscle actin is often positive in nodular fasciitis, helping to distinguish it from CFT (actin immunostains are variably positive in CFT). Additionally, nodular fasciitis has been found to demonstrate a characteristic t(17;22) translocation resulting in a MYH9::UPS6 fusion.

Solitary fibrous tumor (SFT) is another spindle cell mesenchymal neoplasm to be considered. SFT do not typically have calcifications. In addition, SFT are often more cellular, with numerous branching or “staghorn” vessels. Both CFT and SFT express vimentin, while CD34 is variably expressed in CFT but diffusely positive in SFT. Unlike CFT, SFT express STAT6 and CD99, with a NAB2::STAT6 gene rearrangement.

1. Which of the following is true regarding calcifying fibrous tumor (CFT)?
   
   
   1. High risk of local recurrence
   2. Most commonly found in the head and neck
   3. Seen exclusively in men
   4. Usually in young children, with median age at time of diagnosis of 5.6 years
   5. Usually well-circumscribed but unencapsulated and paucicellular
2. What gene alteration is seen in up to 50% of inflammatory myofibroblastic tumors?
   
   
   1. ALK
   2. EWSR1
   3. NAB2
   4. ROS1
   5. STAT6
3. Which immunohistochemical stain can consistently differentiate CFT and solitary fibrous tumor?
   
   
   1. ALK1
   2. CD34
   3. S100
   4. STAT6
   5. Vimentin

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8. Pezhouh MK, Rezaei MK, Shabihkhani M, et al. Clinicopathologic study of calcifying fibrous tumor of the gastrointestinal tract: A case series. Hum Pathol. 2017;62:199-205.

1. Usually well-circumscribed but unencapsulated and paucicellular (e)
2. ALK (a)
3. STAT6 (d)