Cytological Diagnosis and Misdiagnosis of Nodular Fasciitis.

BACKGROUND: Nodular fasciitis (NF) is a rapidly growing, self-limiting, subcutaneous nodular cytologic exuberant fibroblastic/myofibroblastic proliferation prone to cytological misdiagnosis. AIMS: This study aimed at finding out the utility of fine needle aspiration cytology (FNAC) from NF patients and to validate the diagnostic features.
MATERIALS AND METHODS: The study group comprised 11 cases diagnosed as NF on cytology or subsequent histology.
RESULTS: Out of 11 cases, 9 were cytologically diagnosed as NF. Two cases were misdiagnosed as sarcoma as proven histologically. Of the 9 cases of NF, spontaneous resolution occurred in 7 cases in 2-16 weeks; excisional biopsy was undertaken in the other 2 cases.
CONCLUSION: On cytology, NF reveals hypercellular, polymorphic, dispersed cell population, which is most commonly misdiagnosed as sarcoma. For this reason, FNAC has to be correlated with clinical data and followed up for the anticipated spontaneous regression. Copyright:

INTRODUCTION

Nodular fasciitis (NF) is the commonest of the benign pseudosarcomatous lesions.[1] It presents as a rapidly enlarging, often painful or tender subcutaneous nodule, most often affecting young adults and showing a predilection for the upper limb, especially the forearm.[2] Owing to hypercellular, polymorphic pattern of lesional cells and giant cells, NF is the most common benign lesion misdiagnosed as sarcoma on fine needle aspiration cytology (FNAC).[3] We are presenting the FNAC findings in 11 cases of NF patients.

This study was undertaken as NF and is commonly misdiagnosed as sarcoma, so a correct cytodiagnosis will prevent the patient from unnecessary mutilating surgery, as NF undergoes spontaneous regression within few weeks. Various authors in previous studies have also stated that clinical course of NF is completely benign and typically regresses within a few months without surgery or treatment of any kind, it can be very challenging diagnostically, often mimicking a malignant process due to its rapid growth clinically and its high cellularity, mitotic activity and variable/non-specific cytomorphologic findings.[456]

MATERIALS AND METHODS

The study group comprised a total of 11 cases. Nine of these were cases of NF diagnosed cytologically and verified histologically (two cases)/clinically (through regression in seven cases). Two cases had been misdiagnosed cytologically as sarcoma. We performed the standard FNAC procedure using 22-gauge needle. Air-dried smears were prepared and examined on site to determine the adequacy of the samples. Smears were then fixed in methanol and stained with May-Grunwald Giemsa and studied cytologically. Histology and immunohistochemistry with SMA and CD68 were undertaken in four cases. Seven cases underwent spontaneous regression during follow-up period of 16 weeks.

RESULTS

There were 11 cases of NF, comprising 5 males and 6 females, with an age range of 17–40 years. The most common location in our series was upper extremity (6 cases), followed by chest wall (2 cases), 1 case each from lower extremity, neck and from preauricular region. In all the cases, there was a history of rapidly enlarging subcutaneous nodule, ranging in size from 1 to 3 cm. There was a short clinical history in all the cases, ranging from 1 to 4 weeks.

In all the patients, FNAC was performed. Cytological diagnoses and their clinical course are given in Table 1. In 11 cases aspirated, 9 cases were diagnosed as NF and 2 cases were misdiagnosed as sarcoma. These two cases were diagnosed as NF on histology. On clinical follow-up of the 9 cases diagnosed cytologically as NF, spontaneous regression occurred in 7 cases in 2–16 weeks. In the remaining 2 cases, excisional biopsy was undertaken on account of rapid growth, which engendered anxiety in the patient and/or clinician.

Table 1

Clinical follow-up of the 11 cases

Cytological diagnosis	No. of biopsied cases	No. of cases with spontaneous resolution	Total
Nodular fasciitis (09)	02	07	09
Pleomorphic sarcoma (02)	02	00	02
Total	04	07	11

Cytomorphologic features of 11 cases are listed in Table 2. The aspirates were highly cellular in 8 cases; 2 cases had moderate cellularity, while low cellularity was seen in 1 case only. Myxoid stroma was seen in all the cases. The case with low cellularity had abundance of myxoid stroma. Almost all the cases had dispersed cells along with few tissue fragments. Cells were polymorphic, having spindle, round, oval to triangular shape. Cells had cytoplasmic processes and round to ovoid nucleus. Few binucleate/trinucleate cells were seen in all the cases. Nuclear chromatin was finely granular, having one to two nucleoli. There were few cells with abundant cytoplasm, resembling ganglion cells. In most of the cases, few inflammatory cells such as mast cells, lymphocytes, histiocytes and histiocytic giant cells were also seen. Mitotic figures were frequently noted in all the cases, but no atypical mitosis was seen [Figure 1a–c].

Table 2

Cytological features of nodular fasciitis

Cellularity and dispersal	Polymorphism	Ganglion like cells	Mitosis	Cytological diagnosis
Highly cellular with dispersed cells and tissue fragments in a myxoid background	Of moderate degree	Present	Present	Nodular fasciitis
High cellularity with dispersed cells and few tissue fragments in a myxoid background	Of moderate degree	Present	Present	Nodular fasciitis
Moderately cellular with dispersed cells and few tissue fragments in a myxoid background	Of moderate degree	Present	Present	Nodular fasciitis
Low cellularity with few dispersed cells and no tissue fragments in a highly myxoid background	Of mild degree	Absent	Present	Nodular fasciitis
High cellularity with dispersed cells and moderate tissue fragments in a myxoid background	Of moderate degree	Present	Present	Nodular fasciitis
High cellularity with dispersed cells and no tissue fragments in a myxoid background	Of marked degree	Absent	Present	Pleomorphic sarcoma
High cellularity with dispersed cells and moderate tissue fragments in a myxoid background	Of moderate degree	Present	Present	Nodular fasciitis
High cellularity with dispersed cells and no tissue fragments in a myxoid background	Of marked degree	Present	Present	Pleomorphic sarcoma
High cellularity with dispersed cells and moderate tissue fragments in a myxoid background	Of marked degree	Present	Present	Nodular fasciitis
High cellularity with dispersed cells and few tissue fragments in a myxoid background	Of moderate degree	Present	Present	Nodular fasciitis
High cellularity with dispersed cells and moderate tissue fragments in a myxoid background	Of moderate degree	Present	Present	Nodular fasciitis

Figure 1

(a) Smears showing dispersed cells, as well as a tissue fragment in a myxoid background (May Grunwald Giemsa stain, ×100). (b) Aspirate showing polymorphic cells with abundant cytoplasm and finely granular chromatin. Mitotic figure is also noted (May Grunwald Giemsa stain, ×400 (c) Aspirate showing polymorphic cells with few lymphocytes and a histiocytic giant cell (May Grunwald Giemsa stain, × 400)

Histopathology was done in four cases and it confirmed the diagnosis of NF [Figure 2a]. Immunohistochemistry for smooth muscle actin and CD68 was positive in all the four cases and was negative for desmin [Figure 2b]. The diagnosis can be aided by the identification of the USP6-MYH9 gene fusion.

Figure 2

(a) Biopsy showing oval to spindle shaped cells in short fascicles and extravasated erythrocytes (Hematoxylin and eosin, ×100). (b) Nodular fasciitis showing positive immunostaining for smooth muscle actin (SMA), ×200 and CD 68, ×400, while Desmin, ×200 was negative

DISCUSSION

NF is a pseudosarcomatous, self-limiting reactive process composed of fibroblasts and myofibroblasts. It may occur in patients of any age, but is most common in adults 20–40 years of age. NF may occur anywhere on the body, the most common sites being upper extremities, followed by trunk, chest wall and back.[7] It is considered to occur due to unusual proliferation of myofibroblasts triggered by local injury or inflammatory process.[8] In our study, clinical features with regard to age, location and duration of symptoms were similar to those previously published.

NF is most commonly misdiagnosed as spindle cell sarcoma, owing to its rapid growth, high cellularity, cellular as well as nuclear polymorphism and mitotic activity. In our study, 2 cases out of 11 (18 per cent) were misdiagnosed as sarcoma. However, sarcoma can be differentiated from NF on the basis of long duration of history, larger size of tumour, occurrence in late adult life and most frequently on lower extremities. Plaza et al. reported that two-third of their cases had been misdiagnosed as sarcoma.[9] NF has to be clearly distinguished from spindle cell sarcoma on the basis of degree of cytologic atypia, which is marked in spindle cell sarcoma.[10] Wong believe that distinction of NF from sarcoma can be made on FNAC, provided the clinical course is also taken into account.[11]

On FNAC, NF has to be distinguished from other benign and malignant spindle cell neoplasms, such as benign fibrous histiocytoma (BFH), myxoma, inflammatory myofibroblastic tumour (IMFT) and myxofibrosarcoma. NF sometimes presents with multinucleated giant cells and few or no ganglion cell-like cells; it may then be confused with BFH. Short duration of lesion and rapid growth are in favour of NF. Few NF cases show low cellularity with very prominent myxoid change, then diagnosis of myxoma is rendered, but it is deeply located lesion.[1]

IMFT closely resembles NF on cytology, but is commonly intra-abdominal, has bland-looking spindle cells and prominent inflammatory background. Myxofibrosarcoma can be distinguished from NF on the basis of its long history, occurrence in patients above 50 years of age. On cytology, curvilinear blood vessels are characteristic.[1] Various authors have discussed cytologic differential diagnosis of NF and have mentioned features of assistance in distinguishing it from other spindle cell neoplasms.[111213]

NF is a self-limiting reactive process. There are few reports where FNAC was done and spontaneous resolution occurred within 2–16 weeks.[111314] In our study, 7 cases out of 11 (67 per cent) underwent spontaneous resolution within 2–16 weeks, while excisional biopsy was undertaken in 4 cases. Of these 4 cases, 2 were misdiagnosed as sarcoma, while in other 2 cases, excisional biopsy was undertaken to allay apprehension of the patient.

To conclude, NF is a pseudosarcomatous lesion that can be correctly diagnosed if the cytologist is aware of the clinical as well as cytologic features (high cellularity, dispersed cells, cell polymorphism and myxoid background) and the potential for misdiagnosis.

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Conflicts of interest

There are no conflicts of interest.