A Soft Tissue Perineal Tumour in a Perimenopausal Woman with an Unusual Diagnosis

INTRODUCTION

There are a vast number of differential diagnoses we must consider when we approach a case of a perineal tumour in a perimenopausal female. Most doctors would prioritise ruling out a tumour of gynaecological origins, as that would be the most likely diagnosis, given the age and gender of the patient. But this was not a simple case, as the tumour was a soft tissue tumour, possibly of mesenchymal origin. The patient’s menstrual history was not significant, and she had no significant past history or family history either. On further examination, including a digital rectal examination, radiological investigations, a gynaecological consult, and a complete histopathological workup of the patient, the differential diagnosis leaned towards a soft tissue tumour of mesenchymal origin, with the primary suspicion being a myxofibrosarcoma of the perineum, which is an extremely rare case.

According to the World Health Organization (WHO), myxofibrosarcomas are defined as malignant fibroblastic neoplasms characterised by cellular pleomorphism, variably prominent myxoid stroma, and prominent elongated, thin-walled stromal blood vessels.^[1] The most common presentation of this tumour is that it presents as a slow-growing, enlarging, painless mass in the extremities of elderly patients.^[2] They are mesenchymal in origin, but prior to this classification, they were initially grouped under the category of “fibrous histiocytomas.”^[3] Histologically, they are characterised by a mucoid and nodular appearance with a coarse and plexiform capillary pattern.^[4] Some of the common differentials that one must look out for in these cases are low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma, and desmoid fibromatosis.^[5] Myxofibrosarcomas have the highest rate of recurrence among all soft tissue sarcomas, ranging from 20% to 60% after 5 years. They are also most likely to occur in elderly age groups, at 50– 70 years of age.^[6] But as per our knowledge and literature, a myxofibrosarcoma occurring in the perineal region is a very unusual and rare presentation. The patient also presented with this lesion at 44 years of age, which is far younger than the typical age of presentation. The patient is female as well, which adds to the peculiarity of this case since classical cases of myxofibrosarcomas are much more likely to present in male patients instead of female patients.^[7] However, on further histopathological Examination (HPE) analysis and evaluation from a second laboratory (and to our surprise), the final diagnosis turned out to be a soft tissue fibrous tumour of the perineum and not a myxofibrosarcoma, a diagnosis which is also extremely rare for the patient’s demographic background.

The subsequent sections will cover how the other differential diagnoses were ruled out and how the team concluded it to be a case of a solitary fibrous tumour over the original diagnosis of a myxofibrosarcoma of the perineum.

CASE REPORT

A 44-year-old female came to our hospital OPD with the chief complaint of a vague abdominal discomfort like sensation in the left lower iliac fossa for the past 1 month. She did not complain of any altered bowel or bladder habits. She had no significant past medical or surgical history. Her menstrual history was normal, with regular menstrual periods and moderate, painless flow. She is married with 2 children, and there is no significant or relevant family history either.

Physical examination of the patient showed that she was afebrile with a moderate build and with normal vitals. Per abdominal examination was normal. Following this, a digital rectal examination was done. On DRE, a solid, firm, non-tender, immobile, large soft tissue mass was felt in the left perianal region. Anal rectal mucosa was not adhered to the mass. Furthermore, the mass did not feel warm on touch and was painless. There were no other signs of inflammation or necrosis as well. An abdominal and perineal USG was done for the mass [Trans Abdominal sonography (TAS)+, Trans vaginal sonography (TVS)] and showed the following findings, also shown in Figure 1.

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Figure 1:

USG of left adnexal mass measuring 4.8 cm × 3.6 cm × 4.8 cm. USG: Ultrasonography.

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In the left adnexa, a heterogeneous solid lesion measuring around 4.8 cm × 3.6 cm × 4.8 cm with an estimated volume of 44 cc with increased vascularity was noted. The left ovary was not seen separately.

With the USG findings leaning towards a diagnosis of an ovarian mass/tumour, a gynaecological consultation was done for the patient. A per-vaginal and per-speculum examination of the patient was done, which revealed a mass palpable in the left perineal region (similar to the DRE findings) and no other relevant findings of diagnostic value.

Following the USG and gynaecological consult, an MRI of the pelvis was done in the following sections: T2 Coronal, T1 Axial, T2 Axial, T2 Sagittal, and short tau inversion recovery (STIR) Axial, also shown in Figures 2 and 3.

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Figure 2:

MRI pelvis, sagittal view. MRI: Magnetic resonance imaging.

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Figure 3:

MRI pelvis, transverse view. MRI: Magnetic resonance imaging.

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The MRI report showed evidence of a 4.2 cm × 5.2 cm × 4.6 cm [transverse (TR) × anteroposterior (AP) × signal intensity (SI)] sized, well-defined lobulated, septated soft tissue lesion noted in the left ischioanal and ischiorectal fossa. The lesion shows a heterogeneously hyperintense signal on T2Wt and STIR images and isointense signal on T1Wt images. A moderate-sized lobulated and septated soft tissue lesion was noted, occupying the left ischioanal and ischiorectal fossae as described in the USG report. The surrounding fat, as well as muscle, and the opposite ischiorectal and ischioanal fossa appeared to be normal.

There was a strong possibility of a soft tissue neoplasm as per the MRI report, so an FNAC under USG guidance was done for histopathological analysis, which showed atypical neoplastic cells.

Following this, a decision was made to surgically excise the mass and send it for further biopsy and IHC analysis.

First, the patient was anesthetised with spinal anaesthesia, and then she was placed in a lithotomy position to obtain access to the perineum after the anaesthetic took effect. A vertical incision was made over the left ischiorectal fossa to approach the mass, and the mass was removed by en bloc resection, as shown in Figures 4, 5, and 6.

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Figure 4:

Image showing incision made in the left perineum.

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Figure 5:

Image showing removal of mass.

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Figure 6:

Image showing mass sent for further IHC analysis. IHC: Immunohistochemical.

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This initial biopsy report showed features highly suggestive of myxofibrosarcoma. The following tumour markers were noted:

CD34+, Vimentin+, Actin patchy+, EMA−, S100−

Since the tumour was CD34+, further immunohistochemical studies were needed to rule out the possibility of a Gastrointestinal Stromal Tumour (GIST). So the specimen was sent for further IHC analysis, which gave us the following results [including Figure 7]:

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Figure 7:

Image showing first IHC analysis. The resected tumour sent for IHC analysis stained with (a) hematoxylin and eosin and (b) Anti CD 34. IHC: Immunohistochemical.

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CD34+, SMA focal, Stat6+, negative for S100, DOG1, CK, CD117, ERG, SS18.

Ki67 index = 8%

The report was highly suggestive of a low-risk solitary fibrous tumour since the tumour was positive for Stat6 and CD34 and had a low Ki67 index and was negative for S100 or any other tumour markers like cytokeratin or p53 mutations, which are highly indicative of aggressive and/or malignant tumours. A diagnosis of GIST could successfully be ruled out as the tumour was not positive for DOG1 and CD117.

Along with this, a PET scan was done post-operatively, and the following findings were noted:

1. Mild degree of low-grade FDG avid soft tissue stranding was noted in the perineum/pelvis, towards the left side of the midline, representing post-surgical changes.

2. No evidence of abnormal gross FDG avid soft tissue density was noted in the surgical site to suggest residual disease.

3. FDG avid segmental mucosal thickening noted in the sigmoid colon and the rectum with evidence of lumen narrowing, which possibly represented inflammatory strictures.

Following this, another IHC test was done as a final diagnostic panel, in which IHC analysis was done on 12 specimen blocks taken from the left perineal area where the lesion was located. The sections showed a partially circumscribed cellular tumour composed of ovoid to spindle cells arranged in sheets haphazardly and ill-defined fascicles, amidst which branching and hyalinized staghorn like vasculature was seen. Myxoid change, haemorrhage, and collagenous stroma were also noted. Occasional mitosis was also seen, with no significant nuclear polymorphism. No coagulative necrosis was noted. Areas of haemorrhagic infarction were also seen focally. The IHC markers which were positive are as follows [images in Figure 8]:

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Figure 8:

Image showing repeat IHC analysis. The resected tumour which underwent repeat IHC analysis, stained with (a) Anti CD 34 and (b) Anti STAT 6. IHC: Immunohistochemical.

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CD34: Positive

STAT 6: Positive

S-100: Negative

SOX 10: Negative

CD31: Negative

Ki-67: 5%–10%

The patient was then sent for radiotherapy for the tumour, and she, along with her family, received appropriate counselling about the disease status, treatment plan, benefits, adverse effects, and prognosis, and informed consent was taken. She was planned and treated with adjuvant external beam radiation therapy using image guided radiotherapy (IGRT) on Versa with surface-guided RT in two phases, as shown in Table 1.

All dose constraints were achieved, and the treatment period lasted for 33 sessions for a total of 6 weeks. The patient is currently doing well, and her prognosis is favourable as of now.

The patient gave her full written consent for allowing us to take the required information needed for this case review and presentation, and her anonymity will be maintained as per the agreement.

DISCUSSION

This was a very rare case of a solitary fibrous tumour which had conflicting results after different diagnostic workups. The primary diagnosis suspected was a myxofibrosarcoma, which is very unusual since the tumour presented in a completely different age group, as well as in a female patient which is unlikely for most cases for myxofibrosarcomas. According to one study, the median age of myxofibrosarcoma was 67 years, with 71% of patients being male.^[8] Another study showed that the median age was 62 years, with 55% of the patients being men.^[9] Additionally, the typical site of presentation of a myxofibrosarcoma is in the extremities, with only a minority of cases presenting on the trunk and extremities.^[10] The only literature we could find of any similar cases was a case review of a patient with a myxofibrosarcoma presenting on the left buttock of a 77-year-old male patient.^[11] There was another case review of a low grade fibromyxoid sarcoma in the perineum in a patient from Uttar Pradesh, India, which had a very similar presentation and progression as a myxofibrosarcoma.^[12] So, establishing one of the differential diagnoses as myxofibrosarcoma was justified, although the chances of a myxofibrosarcoma presenting in the perineum is extremely rare and not something that we usually consider as a differential diagnosis. And it is also important to differentiate it from a low grade fibromyxoid sarcoma which is shown to have a very similar progression and course.

The diagnosis of a myxofibrosarcoma is typically made based on histopathological findings. They can be classified into three categories: Low grade, Intermediate grade, and high-grade myxofibrosarcomas.^[13] These grades vary based on cellularity and cellular architecture, with low grade tumours having lower cellularity and pleomorphic and hyperchromatic nuclei and a prominently myeloid matrix. The higher the grade of the myxofibrosarcoma, the more is the cellularity and nuclear atypia of cells, and the prognosis becomes worse with grade 3 having the worst prognosis.^[13,14] Additionally, low and intermediate-grade tumours can also display a “pseudo-lipoblast” appearance, characterized by significant intracytoplasmic vacuolization and cellular morphology which closely resembles lipoblasts.^[13] However, these findings clashed with the findings in our case, which prompted more histopathological analysis and IHC reports.

Clinically, Myxofibrosarcomas tend to be very locally aggressive, with chances of distant metastasis being lower but still possible. Several studies have shown that the most common sites of spread or distant metastasis are the lungs, lymph nodes and the mediastinum.^[15–17] Fortunately, there were no signs of metastasis in our patient as she presented to us in the early stages of the disease, when there was initial suspicion of the lesion being a myxofibrosarcoma. However, the possibility of a malignant tumour couldn’t be fully ruled out as the tumour was CD 34 positive which can be seen in soft tissue tumours like rhabdomyosarcomas and leiomyosarcomas.^[18–20]

What solidified the diagnosis of a low-grade solitary fibrous tumour instead of a myxofibrosarcoma were the subsequent IHC analyses and the tumour markers which were detected in them. As shown in our analyses, solitary fibrous tumours typically have ovoid to spindled cells with thin walled, large branching “staghorn” shaped blood vessels.^[20] Along with this, the tumour marker Stat 6 is also a surrogate marker for solitary fibrous tumours, although for reasons unknown it is not directly involved in the pathogenesis of the tumour directly.^[21] Along with this, CD 34 is also a reliable marker for solitary fibrous tumours, which was positive in the IHC analyses we performed.^[20–22]

With that being said, a soft tissue fibrous tumour in the perineal region is still very rare. Soft tissue fibrous tumours only account for less than 2% of all soft tissue tumours in the body, and the most common locations are usually in the thoracic and peritoneal cavities, as well as the extremities and the head and neck regions. These tumours almost never present in the perineal region, with only a few documented cases recorded in our literature.^[20]

CONCLUSION

The main purpose of this case review was to shed light on a very unusual presentation of a soft tissue perineal tumour which was diagnosed as two different tumours by two different laboratories. Both tumours are almost equally rare and yet are vastly different in their clinical courses and prognoses. It is of utmost importance to diagnose such cases as early as possible, in order to prolong the life expectancy of such patients and to make sure that they get the best possible treatment as soon as possible. When we approach such cases, we should also be more open minded about taking multiple opinions from different departments and laboratories, as well as not excluding atypical diagnoses that we generally do not consider in clinical practice.