Primitive Myxoid Mesenchymal Tumour of Nose

Abstract

Primitive Myxoid Mesenchymal Tumour of Infancy (P.M.M.T.I.) is a locally aggressive myofibroblastic tumour, occurring mostly in the first year of life. Grossly, it occurs as a non-encapsulated, multi-nodular tumour with focal infiltrative growth with a size ranging from 2 to 15 cm. It is composed of primitive spindled cells in a myxoid background. It is a low-grade fibroblastic malignancy with low metastatic potential with a high local recurrence rate. On immunohistochemistry, it stains positive for Vimentin. no reactivity for smooth muscle actin, muscle specific actin, desmin, S-100 protein, or myogenin. Electron microscopy documented a poorly differentiated fibroblastic proliferation. The present case is of a P.M.M.T. occurring in the nose of a 3 ½ years old female child. This is the first case reported from Central India. The child had recurrent nasal growth and the excision biopsy was suggestive of intermediate grade fibroblastic neoplasm. The biopsy, on IHC staining, was positive for Vimentin and CD99 and negative for S-100, CD-34 and Desmin, favouring the diagnosis of P.M.M.T. The child had a total of three recurrence of growth after local excision before diagnosis was established. In the prior two surgeries, the histopathological analysis reported it as a benign nasal polyp. After the third surgery, the specimen was sent for IHC. Immunohistochemical stains helped in differentiating it from congenital infantile fibrosarcomas, a similar type of mesodermal tumour. The present case of Primitive myxoid mesenchymal tumour following IHC stains were positive for Vimentin, CD-99, CD-117 and NESTIN, pointing to the primitive nature of the tumour. It was negative for the neural marker. Since it is chemo resistant, the preferred method of treatment is wide surgical excision.

Introduction

Paediatric sarcomas are a heterogenous group of soft tissue tumours. These tumours differ considerably in their prognosis, chemosensitivity and recurrence rates [1]. Primitive Myxoid Mesenchymal Tumour of Infancy (P.M.M.T.I.) is one such undifferentiated sarcomatous tumour, presenting in infancy with fast-growing swelling mostly in extremity, head, and neck and dorsolumbar region. Alaggio et al. first described a series of these tumours in 2006 [2]. P.M.M.T. is a locally aggressive tumour. Special immunohistochemical staining and cytogenetic techniques help in distinguishing it from other paediatric mesodermal tumours. Surgery with wide local excision is the treatment of choice. It is known to recur locally after excision. The tumour doesn't respond to chemotherapy. However, in 2017, Cramer S.L. Li R., Ali S., Bradley J.A., Kim H.K., and Pressey J.G., documented recurrent tumour responding to doxorubicin chemotherapy treatment [3]. In their extensive workup in a recurrent case of P.M.M.T., they reported the tumour to harbour BCOR Internal tandem duplication gene, the same genetic alteration found in clear cell sarcoma of the kidney, hence its response to doxorubicin.

This case is a first case report from India in a 3.5 year-old female child with an aggressive nasal mass arising from the lateral wall of nose reported as P.M.M.T on basis of histopathology and IHC evaluation.

Till now, more than 20 such cases have been documented worldwide, mostly in infants and young children of both sexes. These old published case reports have helped us understand the behaviour of the tumour, its treatment and prognosis. Total three documented cases have been reported in children older than 1 year till date, with this case being the fourth.

This is the first documented case presenting primarily in the nose.

Case Report

Case History

A 3.5-year-old female child from a rural area came with the complaint of recurrent nasal mass present since 8 months.

The child had scanty left nasal bleed 8 months previously followed by a small reddish mass in the left nasal cavity. The nasal mass had rapidly increased in size and not responded to medicine. She underwent local excision of nasal mass twice but immediately after surgery there was a fast recurrence. Postoperative biopsy analysis, both the times, was a benign nasal polyp.

After second local excision, the tumour recurred within a month, following which they came to the tertiary referral centre (Figs. 1, 2).

Fig. 1.

Patient at the time of admission

Fig. 2.

The same patient after 10 days—Visible rapid increase in size mass

On Local Examination

A single, finger-like reddish mass was seen coming out of the left nasal cavity. It measured around 6 × 3 cm and was a soft, noncompressible, insensitive, and non-encapsulated mass. No pulsation was present. On probing, the mass was attached in the middle meatal area with local bleeding present.

The left nasal cavity was blocked and air entry was reduced on the right side.

The oral cavity and palate were normal.

Within 15 days, the mass enlarged rapidly, growing upto 12 cm outside the nose (Fig. 3).

Fig. 3.

Size of nasal mass at the time of surgery

Preoperative C.T. scan of P.N.S. with contrast showing mass occupying left nasal cavity along with the haziness of left maxilla and left ethmoid.

It was non-enhancing mass with no prominent feeder. Externally, the mass reached almost up to hyoid (Figs. 4, 5, 6 and 7).

Fig. 4.

Saggital CT SCAN of the patient showing a mass in the nasal cavity

Fig. 5.

Scan axial cut showing mass up to the hyoid bone

Fig. 6.

Ct Scan in this figure coronal cuts showing opacity in the nasal cavity and lt maxilla

Fig. 7.

MRI Scan

CT Scan at the time of initial surgery showed mass in nose ,nasopharynx and maxilla

Under General Anaesthesia, the nasal mass was surgically removed from its base attached at the Middle Meatus. Through pernasal and endoscope control via C.W.L. approach, Maxillary Sinus was visualised. The mass seemed to arise from the Middle Meatus with the bone of the lateral wall of nose deficient at the attachment of the mass. Endoscopically, the bony Medial Wall of the Maxilla in the Superior Medial aspect was found deficient.

Grossly, the specimen was red and spongy and the intranasal part was pale. On cutting the specimen, the nasal part was like fish flesh. It was sent for H.P.R. The mucopus from the Maxilla was negative for fungal and bacterial culture (Fig. 8). The postoperative course was uneventful.

Fig. 8.

Post operative specimen

The excised mass length was 15 cm.

Postoperative biopsy showed a diffused proliferation of spindle cell with a myxoid background and a fine network of blood vessels, suggestive of Intermediate-grade Fibroblastic Neoplasm.

On immunohistochemical analysis, the biopsy came positive for Vimentin and CD-99 and negative for S-100, SMA, CD-34, and Desmin, thus favouring the diagnosis of a Primitive Myxoid Mesenchymal Tumour of Infancy.

The patient was discharged with advice for a monthly follow up to monitor the patient for recurrence (Fig. 9).

Fig. 9.

Postoperative pic at time of discharge

The first month follow up was normal.

On the second month follow up, the patient came with a small intranasal recurrence but refused admission.

Within three months of surgery, the mass grew into a trilobed mass with nasopharyngeal extension. On examination, her left eye had shifted outwards laterally (Figs. 10, 11 and 12). On palpation, in her medial orbital wall, a firm mass could be palpated along with bony breach of inferomedial orbital wall.her vision was normal.

Fig. 10.

Recurrent nasal mass 3 months after surger at tertiary centre

Fig. 11.

Recurrent nasal mass causing lateral displacement of left eye

Fig. 12.

Recurrent nasal mass with a shifting of the left eye

Figure 13 mass growth in 15 days with the fullness of palate patient was re-evaluated and CT scan and MRI were advised (Figs. 14, 15 and 16).

Fig. 13.

Recurrent nasal mass at the time of readmission

Fig. 14.

Repeat ct images

Fig. 15.

Coronal ct scan is after recurrence

Fig. 16.

MRI Scan

A scan after the present (third) recurrence showed the extensive mass occupying nose Nasopharynx Maxilla Ethmoid with erosion of medial orbital wall on the left side. With the diagnosis of a Primitive Myxoid Mesenchymal Tumour of Infancy, the patient was advised to go to a higher centre but the patient's parents refused.

Revisional surgery with Medial Maxillectomy was done by Weber—Fergussion incision. Preoperative mass was seen filling the nose. Nasopharynx and Medial Maxilla and extending into the eye through a bony defect in the Medial part of Infraorbital margin with disruption in the preorbital.

The mass was excised with a broad margin except for the orbital extension, which had a narrow margin. Excision done with only clinical preoperative judgement, as a facility of the frozen section, was not available.

The patient's mother had been explained the risk of eye involvement in future. The patient's biopsy was subjected to H.P.R. with features consistent with P.M.M.T. She was referred to Oncology and registered for chemotherapy with Etoposide and Cisplatin (Fig. 17).

Fig. 17.

Patient after surgery and chemotherapy in followup

Review of Literature

Nasal masses are relatively uncommon in children. They are broadly categorised into the neoplastic and non-neoplastic congenital lesion and undifferentiated sarcoma representing most of these lesion in the nose.

In children and infants, sarcomas present as congenital foci or mass and appear immediately after the birth in the first year of life with varied clinical presentation.

Undifferentiated paediatric sarcoma thus is a diverse group of tumour contributing 5% of paediatric tumour case. It is possible to differentiate them with advanced diagnostic modalities of immunohistochemistry & cytogenetics. It is also possible to suspect the diagnosis by their clinical behaviour, response of surgery, recurrence, response to chemotherapy.

HLA evaluation, genetic study, immunohistochemistry aid in the diagnosis and make it possible to give required therapy.

Alaggio in 2006 first described P.M.M.T. of infancy, describing it as a locally aggressive myofibroblastic tumour. It is a low to intermediate grade fibroblastic malignancy with low metastatic potential. After surgical treatment, it has a high local recurrence rate.

In his series Alaggio described 6 cases of P.M.M.T., 3 of which had a congenital mass in head & neck, trunk and extremity. The tumour was non-encapsulated and had a multinodular appearance. It had an infiltrative growth pattern. Grossly, the cut surface of the specimen is white and fleshy. Histopathology, demonstrating primitive spindle cell in the myxoid background and delicate vessels. It is reported more in infants.

P.M.M.T. is positive for Vimentin and some case also positive for CD-99/CD-117 but negative for lipoblastic Actin and Desmin. This pattern illustrates the primitive nature of the tumour.

Electron microscopy demonstrates poorly differentiated fibroblastic proliferation.

In the Alaggios series, out of six cases, two were alive without recurrence, one died, one lost to follow up, two had recurrence and metastasis requiring treatment with surgery and chemotherapy [2].

CY David, W Cuthbertson, Kevin Caceres, John Hicks, and Elle M Friedman et al., in the diagnosis of a rare disease, summarised differentiation of primitive mesenchymal tumours of infancy from congenital infantile fibrosarcomas and infantile fibromatosis.

The Primitive Myxoid Mesenchymal Tumour is more common in infants of less than one year having a primitive mesenchymal cell with uniform nuclei with myxoid background and delicate vascularity. These tumours are common in infants presenting with expansile mass prone for recurrence after surgical excision. It has a 72–90% recurrence rate and survival rates of the patient are 70–90%. It has a low potential for metastasis [3].

While congenital infantile fibrosarcoma which occurs in less than 6 years of age is having sheets of spindle cells with recurrent reciprocal translocation (12:15p13q25) causing ETV-6 and NTRK-3 gene fusion. It has a 30% recurrence. Preferred method of treatment is chemotherapy.95% of the patients undergoing this therapy survive [3].

Infantile fibromatosis occurs in children less than one year. It has an infiltrative pattern of fibroblast proliferation, scattered adipocytes and lymphocytes, Beta CTNNB gene mutation has been demonstrated. It can be treated with surgery, and has a 40–69% recurrence rate and the survival rate is 80–85% [3]. A closely monitored meticulous workup is required to evaluate these cases of primitive myxoid mesenchymal tumour of infancy and to differentiate from other similar neoplasms.

Till now more than twenty documented cases of primitive myxoid mesenchymal tumour have been reported[online search].

After Alaggio, in 2012, Qixing reported two cases with a lesion in the head and neck and lumbar region, which on histochemistry was Vimentin, CD-99, and CD-117 positive, indicating the primitive nature of tumour [4].

In 2013 Tzan ping reported P.M.M.T. in the scalp on a 3-month-old Taiwanese child [5]. The histology report showed typical morphology and the tumour cells showed Vimentin and CD99 immunoreactivity. The translocation t(12,15) (p13,q25) was not found by fluorescence in situ hybridization.

In 2013 Saito, Atsuro & Taketani, Takeshi & Kanai reported Sacrococcygeal P.M.M.T. present in a female child at 5 months of age. It was resected when the child was 19 months old. The tumour consisted of a primitive spindle, pleomorphic, nearly round cells. The cells grew in a multinodular manner and had a mucosal stroma. The periphery of the tumour showed high cell density and a delicate vascular network. They concluded it was P.M.M.T., based on pathologic and genetic analyses. C.T. and M.R.I. in their series showed a low absorption and a high signal, respectively, on T2WI findings suggestive of a tumour with an abundant mucosa. Doppler usg showed abundant blood flow in the tumour, which reflected angiogenesis. They said that it is unknown whether these findings are P.M.M.T.I specific because no report has been published previously regarding blood flow and imaging analyses in this tumour type [6].

Guilbert, Marie-Christine & Rougemont, Anne-Laure & Samson, Y & Mac-Thiong, Jean-Marc & Fournet, Jean-Christophe & Bouron-Dal Soglio, and Dorothée. (2014) reported P.M.M.T. conversion into sarcoma in an 8-month-old girl presenting with cervical mass and underwent surgical resection of it. With a post-operative histologic diagnosis of a primitive myxoid mesenchymal tumour of infancy (P.M.M.T.I) more than 5 years after the initial surgical intervention, the tumour recurred locally, with numerous distant metastases. The histologic morphological report of this tumour was suggestive of undifferentiated high-grade tumour thus reporting the first case of a transformation of a P.M.M.T.I into an undifferentiated high-grade sarcoma. Hence the recommended R.T. should be given after surgery [7].

In 2015, Jennifer reported P.M.M.T. in the chest wall of infant and recommended Surgery to be the most effective treatment given the lack of predilection for metastasis and poor response to traditional chemotherapy [8].

In 2017, Dandan et al. reported the first case of omental P.M.M.T. in 2-year-old girl presenting with ascitis, thus emphasising that the disease is not restricted to periphery and head and neck and also summarized nineteen cases of P.M.M.T. reported till then [9]. As awareness of this entity is improving more cases are being reported. As lesion of extremity, neck and head are easily visible, they are more frequently reported.

In 2018 Amna Afzal Saeed et al.reported case of primitive P.M.M.T. of infancy with brain metastasis [10]

Muller et al. described P.M.M.T. in the Thenar eminence. The lesion recurred after conservative excision and was ultimately nonresponsive to chemotherapy, necessitating partial amputation [11]. Recent literature sites P.M.M.T. tumours have BCOR internal tandem duplication, the same genetic alteration detected in clear cell sarcoma of the kidney. The article cites 13-month female with recurrence showing no response to Actinomycin and Vincristine. However patient showed complete response to Doxorubicin-containing therapy along with proton beam radiotherapy [12] thus suggesting BCOR Internal Tandem Duplication gene as a key finding on P.M.M.T. which needs further testing in a recurrent case to correlate.

Lam J. and Lara-Corrales reported it in a preterm infant following excision of congenital juvenile xanthoma [13].

It is mostly tumour of infancy. Till date, only three cases have been reported in a child above one year of age, this being the fourth case.

It still needs to be evaluated why some cases present at post infancy.

Immunochemical studies employing specific immunohistochemical staining and genetic analysis for mutation help to distinguish P.M.M.T. from congenital infantile fibrosarcoma.

P.M.M.T. responds well to surgery with a wide margin.

The usual course of the disease is excision biopsy followed by recurrence. It has to be differentiated from both benign and malignant myofibroblastic disease like congenital infantile fibrosarcoma, infantile fibromatosis, fibromyxoid sarcoma, etc.

A competent and complete pathological work up is a must when dealing with complex disease processes, as the treatment is guided by the correct histological diagnosis.

This case is unique as it is the first reported case in India till date (Net search). This child was 3 ½ years age and 1st case in which progression and the rapid growth was documented with the clinical picture.

Abbreviations

PMMT

Primitive myxoid mesenchymal tumour

IHC

Immunohistochemical stain

CD-99

Tumour marker

CD-112

Tumour marker

Funding

Funding this study was not funded by any source both authors did not receive any grant

Compliance with Ethical Standard

Conflict of interest

Main author and treating surgeon does not have conflict of interest with dr Vijay shrivastav second author who is pathologist reporting histology report dr Vijay pathologist have no conflict of interest with author one dr kavita schdeva under whom patient was admitted and received surgery

Human and Animal Rights

This article does not contain any human study or their participation in clinical trial. There is no animal study involved in this paper

Informed Consent

Consent given by patients mother.