| Abstract|| |
Plexiform fibromyxoma (PF) is a recently described rare type of mesenchymal tumor of the stomach with only 123 cases reported in the literature. It is characterized by a peculiar plexiform growth pattern, myxoid stroma with arborizing microvasculature, and spindle-shaped myofibroblastic cells. We herein report a case of gastric PF in a 15-year-old boy, mimicking a gastrointestinal stromal tumor (GIST) due to overlapping clinicoradiological features. Distinct pathological and immunohistochemical features of PF do aid in distinction from GIST and other mesenchymal entities. Diagnosis is crucial as surgical resection is the mainstay of treatment unlike aggressive management in GIST. It is a benign entity with no local recurrence or distant metastasis reported so far, but confirmation of the same requires longitudinal observational studies with a larger sample size.
Keywords: GIST, mesenchymal tumor, plexiform fibromyxoma
|How to cite this article:|
Goyal S, Beso P, Khullar R, Sakhuja P. Plexiform fibromyxoma of the stomach: An underrecognized entity!. Indian J Pathol Microbiol 2023;66:343-6
| Introduction|| |
Plexiform fibromyxoma (PF) was first described by Takahashi et al. in 2007. The term plexiform “angiomyxoid myofibroblastic tumor (PAMT)” was designated because the condition was morphologically distinct from other gastrointestinal mesenchymal tumors due to its plexiform pattern, abundant myxoid matrix with hypervascularity, and myofibroblastic nature. In 2009, Miettinen et al., described 12 cases of this entity and designated these tumors as “plexiform fibromyxoma” which was later adopted by the World Health Organization (WHO) classification of tumors of the digestive system in 2010 for nomenclature.
To the best of our knowledge, 123 cases have been reported to date, with only twocases from the Indian subcontinent.,, We report a case of PF mimicking gastric gastrointestinal stromal tumor (GIST) clinicoradiologically in a 15-year-old boy, highlighting the importance of accurate diagnosis as it does not require aggressive management, unlike GIST.
| Case Report|| |
A 15-year-old boy presented to the outpatient department, gastrointestinal surgery, with complaints of pain in the abdomen for the last 1 year associated with generalized weakness and fatigue. The pain was dull aching, continuous, and non radiating. There was no history of fever, altered bowel habits, vomiting, hematemesis, and melena. The patient gave a past history of 1 unit of blood transfusion for severe anemia. On examination, he was stable, thin built, with a BMI – 16 kg/m2, and had severe pallor. No icterus or lymphadenopathy was noted. The abdominal examination did not reveal any palpable lump.
Upper gastrointestinal endoscopy revealed submucosal growth with central umbilication in the antrum causing mucosal edema extending till the pylorus.
Contrast-enhanced computed tomography [Figure 1] revealed a well-defined heterogeneously enhancing endophytic soft tissue lesion arising from the posterior wall of the gastric antrum area, measuring 7.2 × 5.1 × 4.0 cm in size. A provisional diagnosis of gastric GIST was considered, and distal gastrectomy was planned. Intraoperatively, the mass was circumscribed in the antro-pyloric region with maintained fat planes posteriorly with the pancreas. Distal gastrectomy with Billroth 1 reconstruction was done. The postoperative period was uneventful.
|Figure 1: (a) Axial contrast-enhanced CT images show heterogeneously enhancing well-defined mass in the gastric antrum (asterisk), arising from the stomach wall with a predominant endophytic component. There was no evidence of gastric outlet obstruction, and fat planes with adjacent viscera were preserved. (b) A circumscribed submucosal polypoidal mass with focal mucosal ulceration was seen in the posterior wall of the antrum. (c) Cut surface revealed a well-circumscribed, multinodular, gray-white tumor within the gastric wall reaching till the serosa. Focal gelatinous areas were noted|
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A partial gastrectomy specimen was sent for histopathology. A circumscribed submucosal polypoidal mass measuring 7 × 4.8 × 4 cm, with focal mucosal ulceration was seen in the posterior wall of the antrum [Figure 1]b. Cut surface revealed a circumscribed, gray-white tumor with gelatinous areas within the gastric wall reaching till the serosa [Figure 1]c. Microscopic examination revealed a multinodular relatively hypocellular tumor comprising bland spindle cells arranged in myxoid to a variably collagenized matrix. The tumor nodules were dissecting the muscularis propria and reaching into the subserosa with pushing margins [Figure 2]a and [Figure 2]b. Individually, the cells were spindle-shaped, with a vesicular nuclear chromatin and inconspicuous nucleoli [Figure 2]c. A rich arborizing capillary network was seen in the stroma. At places, extensive sclerosis and hyalinization were noted [Figure 2]d. No mitoses, atypia, or necrosis were noted. Perigastric lymph nodes showed reactive hyperplasia. On immunohistochemistry (IHC), the tumor cells showed strong cytoplasmic positivity for smooth muscle actin (SMA), focal cytoplasmic positivity for HHF35 and caldesmon and were negative for S-100, CD34, CD117, DOG1, desmin, HMB45, myogenin, and ALK1 [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d, [Figure 3]e, [Figure 3]f, [Figure 3]g. Ki67 labeling index was 1% [Figure 3]h. A final diagnosis of plexiform fibromyxoma was rendered. After 2 months of follow-up, the patient is alive and disease-free.
|Figure 2: H&E section shows (a) A relatively hypocellular tumor comprising bland spindle cells arranged in myxoid to a variably collagenized matrix. (× 100) (b) The tumor nodules were dissecting the muscularis propria and reaching into the subserosa with pushing margins. (×40) (c) Individually, the cells were spindle-shaped, had a vesicular nuclear chromatin and inconspicuous nucleoli. Stroma had a prominent branching capillary network. (× 400) (d) Areas of extensive sclerosis and hyalinization were noted. (× 100)|
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|Figure 3: On IHC, (a) the tumor cells were negative for CD117 ( ×200) (b) DOG1 (× 200). (c)Tumor cells showed strong cytoplasmic positivity for smooth muscle actin (SMA) (× 100), focal cytoplasmic positivity for (d) caldesmon, and e) HHF35 (× 400). Staining was negative for (f) desmin and (g) CD34 (× 200) (h) Ki67 labeling index was 1% (×200)|
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| Discussion|| |
To the best of our knowledge, 123 cases of PF have been reported worldwide tillo date. The recent most case reported in 2020 discussed the cytological diagnosis of PF and its histologic correlation. From India, one case of duodenal PF has been reported in a 19-year-old woman, and the second was a gastric PF in a 51-year-old lady with synchronous bilateral cystic ovarian neoplasms., The estimated frequency ratio of PF: GIST is less than 1:150, which might be partly attributable to misdiagnosis as GIST.
The age range is broad from 5 to 81 years (median –46 years). It is a worldwide disease with maximum cases reported from China (n = 41;33.9%), followed by the United States (n = 29;24.0%). Mostly, it presents as nonspecific complaints or symptoms related to GI bleeding like anemia, melena, and hematemesis.
Typical location of PF is gastric antrum (including pylorus and gastric angle, N = 95; 79.2%), with the body (N = 10; 8.3%) and fundus (N = 4; 3.3%) being uncommon sites. Rarely, it can occur at extragastric sites like duodenum, jejunum, gall bladder, and mediastinum.
Size of tumor varies from 0.8 to 17 cm, (mean = 4.81±3.30 cm). On endoscopy, PFs are typically pink and glistening polypoidal tumors, with ulcerative/smooth mucosa. On macroscopic examination, a classical PF appears as a lobulated gray white unencapsulated, but well-defined mass, gelatinous to cystic cut surface with a multinodular pattern. On microscopic examination, the multinodular growth pattern with plexiform arrangement of bland spindle cells in abundant myxoid stroma with areas of collagenization is characteristic. A rich, arborizing, capillary-sized vasculature is conspicuous in the background. Cellular atypia, mitosis, and necrosis are rarely seen.
Yoshida et al. described delicate collagenization in the center of tumor nodules, emphasizing the spectrum of fibrous, fibromyxoid, and myxoid stromal appearance. Miettenen et al. reported intravascular involvement in four cases of PF. Unlike gastric GISTs, extragastric involvement in the form of subserosal nodules or vascular invasion did not have any adverse significance in PF. Immunohistochemistry shows positive staining for vimentin, smooth muscle actin (SMA), and muscle-specific actin (MSA). Focal positivity with desmin, caldesmon, and CD10 suggests possible myofibroblastic differentiation., Yoshida et al. postulated a smooth muscle differentiation of PF on the basis of dense cytoplasmic staining pattern of desmin, HHF-35, and SMA and absence of the subectoplasmic' '“tram-track” pattern, typical of myofibroblasts in their cases. Focal perinuclear or a dot-like positivity for cytokeratin AE1/AE3 has been reported in two cases, supporting the myofibroblastic cell lineage. Ki-67 labeling index is usually <2%, indicating an indolent behavior.
Unique morphology and characteristic IHC findings are useful in ruling out the differential entities. Rarely, GIST has a prominent myxoid stroma, and it usually does not show the distinctive plexiform intramural pattern seen in PF. DOG-1 and CD117 are always negative that allows PF to distinguish from GIST. The inflammatory fibroid polyp is another close differential that also seems to have a predilection for the antrum. However, it usually forms an intraluminal pedunculated polyp, arises in the submucosa, and consists of bland spindle cells in a myxoedematous inflammatory stroma rich with eosinophils. Positive CD34 immunoreactivity is the key marker, which is negative in PF. The inflammatory myofibroblastic tumor (IMT) mimics PF on morphology and immunohistochemical studies. Lack of a plexiform growth pattern, a predominantly inflammatory stroma, and positive anaplastic lymphoma kinase (ALK) immunoreactivity help to distinguish IMT from PF. Myxoid leiomyoma may have a plexiform, tortuous architecture, but typically contains more solid areas showing a fascicular pattern, cytoplasmic eosinophilia, and diffuse desmin positivity. Negative staining for S-100, epithelial membrane antigen (EMA), neurofilament, cytokeratin, and synaptophysin helps in excluding the neuronal, epithelial, perineural, and neuroendocrine cell lineage.
The distinct genetic profile of PF from GIST is further supported by the complete absence of C-KIT and PDGFRA gene mutations. In a study on genetic analysis of 25 PF cases, three patients harboured a recurrent translocation t (11;12)(q11;q13) involving metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and glioma-associated oncogene homologue 1 (GLI1), and GLI1 polysomy was found in two cases., Overexpression of GLI1 through a recurrent MALAT1-GLI1 translocation or GLI1 upregulation delineates a distinct subgroup of PF involving Hedhehog signaling pathway.,
The mainstream treatment of PF is surgical resection in the form of partial gastrectomy or local excision. Bland cytological features, low proliferative index, and absence of necrosis, vascular invasion, local recurrence, or malignant change in 123 cases reported to date justify its characterization as a benign tumor.,
To conclude, the peculiar plexiform architecture of spindle cell tumor, abundant fibromyxoid stroma with arborizing vasculature, and myofibroblastic phenotype on IHC staining are the unique features of PF. Though rare and has an extremely benign course, it is important to diagnose this entity to avoid misdiagnosis of GIST and unwarranted aggressive treatment.
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Conflicts of interest
There are no conflicts of interest.
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Director Professor and Head, Department of Pathology, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research (GIPMER), New Delhi
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]