The characteristic findings are the mixture of proliferating fibroblasts/myofibroblasts, osteoblasts and osteoclastic giant cells (Fig. 29.12).¹¹ When striated muscle is involved, regenerating muscle fibres (‘muscle giant cells’) are also observed. Experience indicates that a correct diagnosis of PMO may be rendered from the combined evaluation of clinical history, radiological features and FNA findings. Computed tomography is especially valuable for visualising the typical changes. In our experience, PMO may resolve spontaneously a number of weeks after needling.

Fig. 29.12 Pseudomalignant myositis ossificans. (A) A mixture of proliferating fibroblasts/myofibroblasts and reactive osteoblasts (MGG). (B) An osteoclast-like giant cell and proliferating osteoblasts. Note the clear cytoplasmic ‘Hof’ (MGG).

Aspirates from lipomas have virtually the same appearance as aspirates from normal adipose tissue. It is therefore important to know that the needle was actually placed within the mass. If a needle with a stylet is used for deep-seated tumours, contamination with normal subcutaneous fat is avoided.

Typically, smears from lipoma consist of fragments of adipose tissue composed of large cells containing a single vacuole of fat and a small dark peripheral nucleus. Within the fragments a few capillary strands are usually observed (Fig. 29.13). Dispersed lipocytes are uncommon. Inter/intramuscular lipomas often include fragments of ordinary striated muscle. Intramuscular lipoma often infiltrates surrounding striated muscle and in those cases multinucleated regenerating muscle fibres may be observed.

Fig. 29.13 Lipoma. Part of a fragment of adipose tissue. Large fat cells with small, dark nuclei. Thin capillary strands intersect the fragment (MGG).

Lipomas with chondroid metaplasia include fragments of acellular myxoid matrix stained bluish red with MGG, along with the adipose tissue fragments. Occasionally rounded chondrocytes are observed in lacunae in this matrix. Aspirates from lipomas with myxoid degeneration often yield a few drops of colourless stringy fluid. Smears show a blue or bluish red myxoid background matrix containing isolated lipocytes or small clusters of fat cells, in addition to the usual fragments of adipose tissue.

Cytological findings: chondroid lipoma (Fig. 29.15)

Fig. 29.15 Chondroid lipoma. Groups of lipoblast-like cells with uni-or multivacuolated cytoplasm within a myxoid matrix (A: MGG; B: MGG). The tumour cell nuclei are irregular and lobulated (C: H&E).

Although rarely a target for FNA, the cytologic features of chondroid lipoma have been recorded in case reports.^16,17

In spite of the variation in size and shape, the nuclei are benign-looking. One important feature in the differential diagnosis from myxoid liposarcoma is the lack of a plexiform capillary network in the cell clusters.

The main clinical problem is to differentiate the various benign variants from liposarcoma. The main clue to a benign diagnosis is the absence of atypical lipoblasts, but clinical details such as age, site and size are also of importance. In Table 29.2 the various variants of benign lipomatous tumours and the main differential diagnoses for each type is summarised.

Table 29.2 Various variants of benign lipomatous tumours and the main diagnostic pitfalls

The cytological appearance of nodular fasciitis has been previously described.²⁰ The more than 70 examples of nodular fasciitis from the author’s files reveal remarkable similarity from case to case (Åkerman and Domanski, unpublished work, 2007). The most important feature is the wide variation in size and shape of the proliferating fibroblasts and myofibroblasts. Spindle-shaped cells with cytoplasmic processes and fusiform nuclei are the commonest type seen, but plump cells with ovoid, rounded, kidney-shaped or irregular nuclei are also always found.

A further typical finding is the presence of polyhedral or triangular cells with abundant cytoplasm. They have one or two rounded nuclei at the periphery near the cytoplasmic membrane, and closely resemble ganglion cells. In spite of the pleomorphism throughout the smear, the chromatin in all of the cells is finely granular and, although their nucleoli may be very large, it is always possible to identify normal looking fibroblasts and fibroblasts with minor reactive changes (Fig. 29.20).

Fig. 29.20 Nodular fasciitis. (A) A myxoid background matrix with dispersed fibroblasts/myofibroblasts displaying moderate variation in shape and size (MGG). (B) Two binucleate cells, closely resembling ganglion cells, and one normal fibroblast (H&E).

This rapidly growing lesion is often painful and tender and most cases are needled in the early phase of growth. Experience indicates that nodular fasciitis often decreases in size or even vanishes in 3 or 4 weeks. When the clinical findings are of a rapidly growing, tender, firm subcutaneous tumour, and the cytological appearances are typical, our policy at present is clinical observation, thereby avoiding surgical intervention.

Two other less common and occasionally needled benign pseudosarcomatous lesions are proliferative myositis/fasciitis. They predominantly develop in adults, proliferative myositis occurring mainly on the trunk, while fasciitis is more common on the extremities. These two lesions share cytological findings with nodular fasciitis, although the myxoid background matrix is less prominent and the large mono- or binucleated cells resembling ganglion cells are numerous and often feature large prominent nucleoli (Fig. 29.21).

Fig. 29.21 Proliferative myositis. A characteristic cell; large, rounded and binucleate with abundant cytoplasm and nuclei opposite each other (MGG).

The cytological appearance of desmoid fibromatosis has been described in a series of 69 cases.²¹ The cases from our files have all shown similar features as described. Due to the often abundant collagenous stroma, desmoid fibromatoses are very firm to palpate and a rubbery resistance is felt when needling. Often vigorous aspirations are needed to collect sufficient material for examination. A finding common to all our cases has been the presence of quite numerous fragments of collagenised stroma staining bluish-grey with MGG and showing a faintly fibrillary background (Fig. 29.22A). Stripped nuclei are also commonly seen. The nuclei are elongated or ovoid with finely granular chromatin and small nucleoli (Fig. 29.22B). Preserved cells have well-demarcated pale cytoplasm, often with unipolar or bipolar cytoplasmic processes. The cells appear in small cohesive clusters or are dissociated. Sometimes faintly outlined nuclei are seen in the stromal fragments. When infiltration of striated muscle occurs, ‘muscle giant cells’ are found.

Fig. 29.22 Desmoid fibromatosis. (A) Part of a fragment of collagenased stroma with faintly outlined fibrillar background and scattered nuclei (MGG). (B) A cluster of loosely attached fibroblast-like cells with ovoid nuclei and greyish-blue cytoplasm (MGG).

Important diagnostic pitfalls arise when the cellular yield is poor and stromal fragments are lacking. Monophasic synovial sarcoma and low-grade malignant peripheral nerve sheath tumour (MPNST) as well as low-grade fibromyxoid sarcoma may be cytologically misdiagnosed as desmoid tumour and vice versa. Other differential diagnoses include nodular fasciitis, neurilemmoma and soft tissue leiomyoma. The uniform spindle cell population, fragments of collagenised stroma, absence of a myxoid background and ganglion-like cells exclude nodular fasciitis; while tumour tissue fragments with elongated or comma-shaped nuclei in a fibrillar background are the hallmarks of neurilemmoma rather than desmoid tumour.

Cytological findings: haemangiopericytoma(Fig. 29.23)

Fig. 29.23 Haemangiopericytoma. A vessel fragment surrounded by tumour cells with ovoid or rounded bland nuclei (MGG).

Cytological findings: extrapleural solitary fibroustumour (Fig. 29.24)

With regard to haemangiopericytoma as well as extrapleural solitary fibrous tumour, the most important pitfall is monophasic synovial sarcoma, other differential diagnoses are low-grade fibromyxoid sarcoma and low-grade malignant peripheral nerve sheath tumour. A clue to a correct diagnosis is the immunophenotype CD34+, CD99+, bcl-2+ (Fig. 29.24B). As is evident from the cytological findings tabulated above and the common immunophenotype, the distinction between haemangiopericytoma and solitary fibrous tumour in FNA is very difficult, sometimes impossible.

Fig. 29.24 Solitary fibrous tumour of soft tissue. (A) A fascicle of tightly packed cells with bland looking fusiform nuclei (H&E). (B) Cell block preparation stained with CD34 (immunoperoxidase).

The cytology of elastofibroma has been described in a small series of five patients.²⁵ The most important clue to the diagnosis is the presence of the degenerate elastic fibres (Fig. 29.25).

Fig. 29.25 Elastofibroma. Degenerated elastic fibres with serrated edges (H&E).

The variable histological features of fibrous histiocytomas are reflected in the cytological findings in aspirated smears. A common picture is the dual presence of fibroblastic cells with ovoid or elongated nuclei and histiocytic cells, which have rounded or irregular nuclei and rather abundant cytoplasm. Giant cells of Touton type, with their characteristic peripheral circle of nuclei, are almost always found, as are deposits of haemosiderin in the histiocytic cells (Fig. 29.26). Capillary strands may be observed. One large series of the cytology of the various types of benign fibrous histiocytoma has been published.²⁶

Fig. 29.26 Fibrous histiocytoma. A group of loosely attached fibroblast-like cells mixed with histiocytes with cytoplasmic haemosiderin deposits (MGG).

Cytological findings: localised tumour of tendon sheath (Fig. 29.27)

Fig. 29.27 Localised tumour of tendon sheath. Dispersed rounded cells with rounded nuclei exhibiting moderate cellular pleomorphism and two osteoclast-like giant cells (A: H&E; B: MGG).

Various benign fibroblastic/myofibroblastic tumours in infancy and childhood are described in the current literature. The two of these entities most often sampled by FNA are fibromatosis colli and fibrous hamartoma of infancy.

The mixture of fibroblasts and regenerating muscle fibres is typical (Fig. 29.28). Most cases of fibromatosis colli regress spontaneously; conservatory treatment as physiotherapy and stretching is recommended and surgical intervention is not necessary in most cases. The cytological features of fibromatosis colli have been investigated in two series, comprising 16 tumours.^27,28

Fig. 29.28 Fibromatosis colli. A regenerating muscle fibre with multiple nuclei surrounded by fibroblast-like cells (MGG).

The cytological features of fibrous hamartoma of infancy have been reported in case reports²⁹ and we have one case recorded in our files (Fig. 29.29).

Fig. 29.29 Fibrous hamartoma of infancy. In a partly myxoid background normal adipose tissue mixed with clusters of spindly cells (MGG).

There are numerous reports of the typical cytological features of neurilemmoma and there is also one correlative cytohistological study of 116 tumours.³⁰ A characteristic clinical sign is the sharp, sometimes radiating pain experienced by the patient on needling. Smears vary in cellularity, usually consisting of numerous tissue fragments of different size. The fragments also vary in cellularity and have irregular borders, so that at low magnification they have been compared with pieces of a jigsaw puzzle (Fig. 29.30A). The cytological findings generally correspond to Antoni A tissue: the fragments consist of cohesive cells with very indistinct cell borders and spindle-shaped nuclei with pointed ends. Small cells with rounded ‘lymphocyte-like’ or ovoid nuclei are also seen (Fig. 29.30B). A number of the elongated nuclei are comma-shaped or have one end bent like a fishhook. Variation in nuclear size is always seen and may be marked. Palisading of nuclei and Verocay body structures are sometimes observed. Dispersed cells are uncommon and mitoses are almost never seen. Another typical feature is a fibrillary background substance in which the cells are embedded. This background is best visualised by H&E staining (Fig. 29.30C). Some neurilemmomas yield a small amount of cystic fluid when aspirated. In other cases dispersed cells are embedded in a myxoid background and the tumour fragments are small with less cohesive tumour cells mingling with histiocytes. These findings correspond to Antoni B areas on histology.

Fig. 29.30 Neurilemmoma. (A) A tumour tissue fragment with irregular borders with varying cellularity. (MGG ). (B) Small cells with rounded ‘lymphocyte-like’ nuclei are occasionally seen in the tumour fragments (MGG). (C) A Verocay body like structure. Note the fibrillar back ground (H&E).

Aspirates from neurofibromas may have an abundant myxoid background and dispersed cells are often more common than tumour tissue fragments. Other than this, the findings are similar to those of neurilemmomas.

The cellular yield is usually good, consisting of tumour cells with abundant but fragile cytoplasm and stripped nuclei are therefore common. In preserved cells, the cytoplasm is typically granular, staining eosinophilic with H&E and blue with MGG (Fig. 29.31). The chromatin structure in the rounded nuclei is uniformly regular and nucleoli are quite small but prominent. A study of the cytological features of 17 granular cell tumours has been published.³¹

Fig. 29.31 (A,B) Granular cell tumour. The tumour cells have abundant granular cytoplasm and rounded bland nuclei with prominent nucleoli (A: H&E; B: MGG). (C) ThinPrep-preparation stained with S 100 protein (immunoperoxidase).

The most difficult problem lies in correctly diagnosing the so-called ancient neurilemmoma, which is easily mistaken for sarcoma. The large cells with pleomorphic, hyperchromatic sometimes bizarre nuclei typical of an ancient neurilemmoma are deceptively like sarcoma cells. However, careful inspection of the enlarged nuclei reveals degenerative changes, including the so-called ‘kern-loche’, which are large intranuclear vacuoles usually present if looked for carefully (Fig. 29.32A). Mitoses are not observed cytologically. According to our experience, leiomyosarcoma and malignant peripheral nerve sheath tumour (MPNST) are the most common false positive diagnoses of sarcoma with regard to neurilemomas with Antoni A features and ancient neurilemmoma.³⁰ Neurilemmoma and neurofibromas with a myxoid background matrix in smears may be misdiagnosed as a number of other soft tissue tumours exhibiting a similar background. These are listed in Table 29.3.

Fig. 29.32 Ancient neurilemmoma. (A) Tumour cells with anisokaryosis and a typical bizarre cell with degenerative nuclear changes (‘kern-loche’) in lower left corner (MGG). (B) Cell block preparation from the same case stained with S 100 protein. (Immunoperoxidase).

Table 29.3 Soft tissue tumours with a myxoid background matrix. Important cytological features in the differential diagnosis

A correct diagnosis of neurilemmoma and granular cell tumour can be confirmed by immunocytochemical staining with S-100-protein and anti-desmin. Ancient neurilemmoma and granular cell tumour display strong S-100 positivity and are desmin negative (Fig. 29.32B, C). MPNSTs usually show only focal S-100 positivity or are negative in contrast to diffuse staining of neurilemmoma and neurofibroma.

The rich cellular yield of granular cell tumour and large numbers of naked nuclei with prominent nucleoli seen in these lesions have been misinterpreted as malignant in smears. In fact, malignant granular cell tumours are very rare, and the key to the correct diagnosis lies in awareness of the characteristic cellular features of the benign lesion.³¹

The most important differential diagnosis is adult rhabdomyoma. Immunocytochemically granular cell tumour is characterised by positivity for S 100-protein, NSE and inhibin.

Cytological findings: angioleiomyoma (Fig. 29.33)

Fig. 29.33 Angioleiomyoma. A small group of spindle cells with blunt-ended bland nuclei with small nucleoli (H&E).

According to our experience, angioleiomyoma is difficult to diagnose correctly in FNA smears. Only one study comprising 10 cases has been published and none of these cases were correctly diagnosed as angioleiomyoma, the majority having been diagnosed as a benign soft tissue lesion or tumour of other histotype.³²

FNA features of deep-seated leiomyoma are limited. In our experience, the most important clue to the diagnosis is the characteristics typical of smooth muscle cells including blunt-ended, ‘cigar-shaped’, elongated or ovoid nuclei of varying size, nuclei are often truncated and sometimes contain vacuoles. The chromatin is finely granular and nucleoli small. The cytoplasm in preserved dispersed cells is light grey to blue on MGG staining (Fig. 29.34). Mitoses should not be present.

Fig. 29.34 Soft tissue leiomyoma. The tumour cells have faintly stained grey-blue cytoplasm and blunt-ended uniform nuclei (MGG).

There are two important differential diagnoses: low-grade malignant leiomyosarcoma and extra-abdominal desmoid fibromatosis. At low power magnification, the overall pattern in smears is similar in leiomyosarcoma and desmoid fibromatosis; a mixture of dispersed cells and cell clusters, many stripped nuclei and stromal fragments. The presence of single mitotic figures and/or focally more than marked anisokaryosis should warn the cytopathologist against making a definitive diagnosis of deep leiomyoma.

The cytological findings on FNA have been published³⁴ and in our files we have FNA smears from more than 30 tumours. Characteristically, the aspirate consists of a few drops of stringy myxoid colourless fluid, not easily spread. This fluid is blue or violet on MGG and faintly eosinophilic on H&E stains. The cellularity is generally poor. Dispersed cells mingle with a few tissue fragments of loosely attached cells in the myxoid background matrix (Fig. 29.37A). The cells are usually elongated, with cytoplasmic processes which may be extremely long (Fig. 29.37B). They have ovoid, elongated or sometimes rounded nuclei. Cells with rounded nuclei may have abundant triangular or polyhedral cytoplasm, blue or violet with MGG stains, and which may contain a single large vacuole or sometimes several. Binucleated cells may also be found. The chromatin texture is uniformly finely granular and nucleoli, if any, are small. A few vessel strands may be observed in the background matrix.

Fig. 29.37 Intramuscular myxoma. (A) Overview: an abundant myxoid background matrix and myxoid tumour fragment containing spindle cells with bipolar cytoplasm (MGG). (B) The typical myxoma cell has very long, thin cytoplasmic processes (H&E).

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