Solitary Fibrous Tumor of the Adrenal Gland: A Multi-Institutional Study of 9 Cases With Literature Review

Abstract

INTRODUCTION

Solitary fibrous tumors (SFTs), primarily pleura-based mesenchymal neoplasms, have also been reported at various extrapleural sites.^1,2 The SFT was first described by Klemperer and Coleman³ in the 1930s as a primary pleural neoplasm. The SFT has no sex predilection, and this tumor has a wide age range, with a peak incidence between 40 and 70 years of age.^2,4 These neoplasms are characterized by inv12(q13q13)-derived NAB2::STAT6 fusion, resulting in the nuclear expression of STAT6.⁴ The features associated with aggressive behavior include nuclear atypia; hypercellularity; necrosis; mitoses exceeding 4 per 10 high-power fields (HPFs; 2 mm²); location in the chest, abdomen, or pelvis; and TERT promoter mutations.^5,6 Later, the modified 4-variable risk stratification model, which incorporated age, tumor size, mitotic count, and necrosis, used to predict the aggressive behavior and metastatic propensity of SFTs was used to stratify the individual tumors.⁷ This system, devised by Demicco et al,⁴ was easily adapted and correlated with the follow-up data compared with the previously set criteria for aggressiveness.

Primary SFT of the adrenal gland is rare: only 12 cases have been reported in the literature to date, predominantly as isolated case reports, and 1 case each in a series of SFTs of the genitourinary system, papillary SFTs of different sites, and a series of adrenal lesions. The reported cases are indeed an underestimation of the true incidence of this uncommon tumor because isolated case reports are no longer considered for publication in the majority of journals. Moreover, the diagnoses were based solely on morphology and CD34 immunohistochemistry (IHC). STAT6 IHC and molecular confirmation by fluorescence in situ hybridization (FISH) were performed in only 2 patients.^8,9 Also, the risk stratification model to assess the risk of metastasis was not described in any of the previously described tumors.

Adrenal gland as the primary site for an SFT should be established after exclusion of neoplasm at a distant or an adjacent site or organ. The unique site prompted a multi-institutional collaboration to comprehend the overarching demographics, clinical and follow-up, macroscopic, microscopic, IHC, and FISH features of 9 additional patients with SFT of the adrenal gland. In addition to a comprehensive review of the literature, the clinicopathologic characteristics exclusive to these SFTs’ occurrence in the adrenal gland have been elucidated. Also, we discuss the differential diagnostic possibilities and metastatic potential based on the risk stratification system of these tumors.

MATERIALS AND METHODS

A retrospective computerized search was conducted at the respective institutions after approval from the institutional review board. Nine patients with adrenal SFT were identified based on the primary site of initial presentation after excluding any synchronous tumor at the time of final pathologic diagnosis. The demographic, clinical, imaging, histopathologic (macro- and microscopic), IHC, FISH, and follow-up data were recorded. The H&E- and immunostained slides were reviewed independently by the pathologists who contributed the cases.

The immunostained slides reviewed included CD34, STAT6, BCL2, CD99, epithelial membrane antigen (EMA), smooth muscle actin (SMA), GATA3, TLE1, pancytokeratin (CK), calretinin, inhibin, S100, and Ki67. The results were recorded semiquantitatively. A cytoplasmic and membranous staining pattern in the tumor cells was labeled as positive for CD34, CD99, SMA, EMA, CK, and BCL2, while nuclear staining was considered positive for STAT6, GATA3, TLE1, and Ki67. Scant granular background staining of the tumor cells was considered negative. At least 5% tumor cell staining was considered positive, and anything less than 5% was labeled negative. The intensity of the immunoreactivity was interpreted as weak, moderate, and strong. Further, the extent of immunostaining was evaluated based on the proportion (percentage) of tumor cells showing a positive reaction and were broadly divided into 4 categories: 0 = no or <5% tumor cell staining; focal = 5% to 10% tumor cell staining; multifocal = 11% to 50% tumor cell staining; and diffuse = >50% tumor cell staining. An H-score was calculated for each stain by multiplying the intensity score with the percentage of the tumor cell showing positivity. The maximum value of the H-score was 300. A manual counting was done on camera-captured images of Ki-67 “hotspot,” including at least 500 tumor cells.

FISH analysis for NAB2::STAT6 fusion was performed on the formalin-fixed, paraffin-embedded tissue sections with 4-µm thickness. The STAT6 break-apart probe was designed to detect rearrangements in the STAT6 gene mapping to chromosome band 12q13.3. In addition to revealing breaks, which could lead to translocation of parts of the gene, inversion, or its fusion to other genes, the probe set could be used to identify other STAT6 aberrations, such as deletions or amplifications. The following guidelines were followed for assessment and interpretation. The tumor areas (as highlighted by the pathologist on the H&E-stained slide) were evaluated on the hybridized slides for the specificity of hybridization, probe signal intensity, and signal-to-background ratio to determine whether the hybridization was optimum for analysis. The low-power (×10) analyses were based on the abundance of abnormal cells, even distribution and the presence of few overlapping abnormal nuclei, and the presence of heterogeneity (presence of subclonal changes), whereas the high-power (×60 or ×100) analyses helped in the assessment of nonoverlapping, distinct, and nondisrupted nuclei with bright, uniform 4',6-diamidino-2-phenylindole staining, a score of nuclei of a similar size to avoid truncation effect, and avoidance of autofluorescent structures. The slides and areas that passed the aforementioned criteria were enumerated for fluorescent signals. STAT6 break-apart (red/orange and green) signals were enumerated on their own using a single band-pass filter. It was started with 1 probe, followed by an enumeration of the signals in each cell, and then was proceeded to the green filter for the other. This process was followed by checking under the dual–band-pass filter to look for a fused yellow signal. The number of signals in the nucleus was recorded on the score sheet. Inconclusive cells were not counted. One hundred to 200 abnormal cells were counted. A valid preparation showed bright signals in more than 90% of the cells. Similar-sized nuclei were chosen to avoid the truncation effect, and autofluorescent bodies were distinguished. When the abnormal cells had been scored, the number of fused (yellow, normal pattern) and discrete individual (red/orange and green, split signal) signals/cells were counted. If the percentage of tumor cells with split signal was 10% (10/100), the sample was considered positive. The FISH result was considered noninformative in the following cases: slides having fewer than 50 scorable abnormal cells, slides with no or patchy hybridization, and slides with high background or autofluorescence that interfered with signal enumeration.^10,11

The modified 4-variable risk stratification model incorporating age, tumor size, mitotic count, and necrosis used to predict the aggressive behavior and the metastatic propensity of SFT was used to stratify the individual tumors.⁴ Individual scores were assigned to each entity as follows: patient age younger than 55 years (0 point), patient aged 55 years or older (1 point); tumor size smaller than 5 cm (0 point), 5 to 9 cm (1 point), 10 to 14 cm (2 points), or 15 cm or larger (3 points); mitotic count per 10 HPFs or 2 mm² 0 (0 points), 1 to 3 (1 point), or 4 or more (2 points); and tumor necrosis less than 10% (0 point) or 10% or more (1 point). Risk classes of low, intermediate, and high were assigned to the tumor, with overall scores of 0 to 3, 4 to 5, and 6 to 7, respectively.

All previously reported cases of adrenal SFT were identified from an extensive literature search and tabulated for comparison with the present series of cases.

RESULTS

Demographics and Clinical Characteristics

Nine patients (6 men and 3 women) diagnosed with primary adrenal SFT were studied in this cohort. The mean age at presentation was 49.3 years (range, 19-64 years), with 4 patients younger than 55 years and the rest 55 years of age or older. The presenting symptoms were as follows: abdominal pain (n = 4); hypertension (n = 3); hypertension and diabetes (n = 1); and abdominal pain, fatigue, and fever (n = 1). Imaging was available in all 9 patients and revealed unilateral (right, n = 4; left, n = 5), well-circumscribed, and homogeneous adrenal masses on computed tomography scans; no heterogeneity or infiltrative margin was appreciated TABLE 1 and FIGUREs 1A and 1B.

FIGURE 1

Contrast-enhanced computed tomography: axial (A) and coronal (B) venous-phase images showing a well-circumscribed homogeneously enhancing left adrenal lesion (arrows), with no evidence of necrosis, fat density, or calcification within it. The right adrenal gland was normal.

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Histopathologic Features

Macroscopic Features

Resection (adrenalectomy) specimens were available in all 9 patients. The specimens weighed between 18 g and 80 g (mean, 36.3 g). The maximum dimension of the tumors ranged from 2 cm to 10.5 cm (mean, 5.1 cm). The tumors were well circumscribed, with solid, homogeneous, and tan-white to tan-yellow cut surfaces. Two tumors had focal cystic areas. None of the tumors showed necrosis TABLE 1.

Microscopic Features

All tumors were well circumscribed, without a capsule, and the tumor cells were arranged in a patternless architecture. Additionally, 3 tumors had a focal storiform pattern. The tumor cells were predominantly spindle with mild nuclear atypia. Ropy collagen and staghorn-like pericytic blood vessels were observed in all tumors. Variable degrees of myxoid change were seen. The mitotic activity ranged from 1 to 5 per 2 mm². Two tumors showed mitoses greater than 4 per 2 mm². Neither epithelioid nor round cell histology nor necrosis was identified in any of the tumors. All tumors were confined to the adrenal gland (pT1) TABLE 1 and FIGUREs 2A and 2B, FIGURE 3A. None of our cases showed capsular or extracapsular extension.

FIGURE 2

A, Adrenal gland with a well-circumscribed spindle cell neoplasm (H&E, ×100). B, Tumor cells were arranged in a patternless architecture, with mild nuclear atypia (H&E, ×400).

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FIGURE 3

A, Staghorn-like pericytic blood vessels were observed (H&E, ×40). B, Diffuse and strong CD34 expression in the tumor cells (immunoperoxidase, ×200). C, Diffuse and strong STAT6 expression in the tumor cells (immunoperoxidase, ×200). D, Tumor with translocation affecting the STAT6 gene (locus 12q13), as indicated by 1 orange/green fusion signal, 1 orange signal (STAT6 gene), and 1 separate green signal (fluorescence in situ hybridization, ×60).

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Immunohistochemical Features

Diffuse and strong nuclear STAT6 expression was observed in all 9 tumors, confirming the diagnosis. CD34 positivity was focal and strong in 1 tumor and diffuse and strong in 6 tumors, while 2 tumors were negative FIGUREs 3B and 3C. The Ki-67 proliferation index ranged from 2% to 15%. BCL2 was positive in all 9 tumors, and CD99 was positive in 8 tumors, except case 6. An EMA test was performed in 2 tumors that showed focal staining. Two tumors where SMA testing was performed revealed focal staining. GATA3, calretinin, inhibin, and S100 were performed in 1 tumor and were negative. The same tumor showed a mosaic pattern of nuclear positivity for p53, confirming a wild type expression for p53.

FISH Findings

The break-apart signals for NAB2::STAT6 gene fusion were detected in 3 tumors where FISH was performed TABLE 1 and FIGURE 3D.

Risk Stratification

Tumor risk stratification based on the 4 variables classified 8 tumors as low risk (88.9%; total score ranged from 2 to3 based on age, tumor size, mitoses, and necrosis) and 1 (11.1%) tumor as intermediate risk (age = 58 years; tumor size = 10.5 cm; mitoses = 3/2 mm²; necrosis = absent; total score = 4) for the assessment of metastatic propensity TABLE 1.

Treatment and Follow-up

All nine patients (100%) underwent surgical resection only. No adjuvant chemotherapy was administered. The follow-up data were available in 7 patients and ranged from 7 months to 23 months, with a mean of 14 months. All 7 patients were alive and showed no signs of recurrence or metastasis TABLE 1.

DISCUSSION

Primary SFTs of the adrenal gland are rare tumors, with 12 patients with primary tumors of the adrenal gland reported in the literature over the years TABLE 2.^8,9,12-21 Much of the current understanding of the disease is derived from similar tumors occurring at other anatomic locations.^22-24 Herein, we include 9 additional patients to the literature, with a focus on understanding the histologic features, immunoprofiles, risk stratification score, and age-dependent differential diagnoses at this anatomic location. The biologic potential of tumors occurring in the bladder and a comparison of cases published in the literature are discussed, as well. The present study is unique because it is the largest case series of primary SFT of the adrenal gland reported in the literature thus far with STAT6 immunoexpression in tumors. Additionally, we have attempted to assess the metastatic behavior of these tumors (also published along with the present series) based on the novel risk stratification model Demicco et al⁴ proposed. These tumors were worked up in a complete and systematic manner, taking into account a broad range of differential diagnoses of SFTs and other spindle cell tumors in the adrenal gland.

In general, SFTs occur in adults between 40 and 70 years of age without a predilection for sex.¹ Combining our cohort of adrenal SFT with the 12 previously published cases, the patients ranged from 13 to 71 years of age (mean, 47.6 years). Six patients were younger than 40 years and 15 were older than 40 years of age. Thirteen patients were younger than 55 years of age and 8 were 55 years of age or older.^8,9,12-21 A slight male preponderance was observed, with a male-to-female ratio of 1.6:1. Tables 1 and 2. No significant associated risk factors were identified in any of the 21 patients, including the 9 cases of the current study. Although there have been rare documented cases of hypoglycemia associated with SFTs, the symptom resolved after the complete resection, which might represent a component of Doege-Potter syndrome or paraneoplastic syndrome because of the release of insulin-like growth factor. No such presentation occurred in our patients or the previous cases of adrenal SFTs.²⁵

The patients are usually asymptomatic, the SFTs are usually detected incidentally at routine screening, and the symptoms of the abdominopelvic SFTs are usually the result of the pressure effect. This slow-growing and indolent tumor arising in the adrenal gland remains undetected until the imaging studies uncover an anatomically ubiquitous tumor.² In our study, 4 of 9 patients complained of dull, aching abdominal pain. Interestingly, this symptom was associated with tumors larger than 5 cm, elucidating their mass effect. The youngest patient in our cohort, aged 19 years, presented with hypertension; the tumor showed microscopic features of aggressive morphology in a spindle cell neoplasm characterized by high mitotic activity. Likewise, another case of SFT with high mitotic activity and necrosis was reported by Yao et al in 2019,⁹ where the patient was hypertensive. Unlike the patient in our cohort, however, this patient was older (>65 years), and true papillae lined by cuboidal cells were the predominant tumor morphology. Hypertension and SFT are exclusive events and cannot be explained as a paraneoplastic effect. In such a scenario, hypertensive, bilateral adrenals should be examined to detect functional pheochromocytoma.²⁶ There was only 1 case of pediatric SFT of the adrenal gland (girl aged 13 years) TABLE 2 among the 21 patients. She presented with low-grade, intermittent fever; dull right abdominal pain; and a progressively increasing right abdominal mass. The tumor was of intermediate risk type.

Tumor size ranged from 2 to 19 cm (mean, 7.9 cm; available in 20 tumors, which includes the present cohort and previously published cases).^8,9,12-21 None of the tumors in our cohort showed necrosis, whereas it was present in 2 of the previously reported cases.^20,21 The case reported by Gebresellassie et al²⁰ had a large tumor (maximum dimension = 19 cm), which could explain the macroscopically depicted necrosis in the center of the tumor. Mitotic activity, however, also an indicator of aggressiveness, was infrequent in this case. Another case of papillary SFT⁹ showed an association between the high mitotic count and the microscopic necrosis in a comparatively smaller tumor (6 cm in maximum dimension). All tumors were well circumscribed, without a capsule, in the 13 tumors where macroscopy was available (our cohort and previously published). Monomorphic spindle cell histology was seen in 19 tumors, while 1 tumor each had round and cuboidal features (our cohort and previously published). The tumor with cuboidal cells revealed marked nuclear atypia. Of note, the spindle cell tumors showed the classic histology of an SFT, whereas the tumor with round cell morphology had a sheet-like arrangement and the tumor with cuboidal features showed true papillae and microcystic areas. The mitotic activity ranged from 1 to 23 per 2 mm². Except for the tumor with cuboidal histology, necrosis was not identified in the 19 tumors studied. The same had 23 mitoses/2 mm² and marked nuclear pleomorphism. All tumors were confined to the adrenal gland (pT1) TABLE 1 and FIGURES 1B-1D.

In the past, in the absence of IHC and molecular advancements, a variety of terminologies, such as hemangiopericytoma, fibrous mesothelioma, pleural fibroma, and solitary fibrous mesothelioma, were used synonymously to refer to tumors exhibiting patterns of SFTs.^2,27 A multitude of cytoarchitectural features seen in SFT, regardless of the anatomic location, warrant ancillary workup to confirm the diagnosis and avoid erroneous therapeutic and prognostic consequences.

SFTs are known to have a myriad histologic patterns, with variable cellularity. The neoplastic cells are spindle to round to epithelioid, arranged in hypo- and hypercellular areas and intervening collagen bands. They are usually described as “patternless” tumors, along with the branching thin-walled blood vessels.^3,28 The spindle cell morphology in adrenal SFTs should be differentiated from other primary spindle cell neoplasms of the adrenal glands, which include benign spindle cell tumors (perineurioma, schwannoma, and leiomyoma), spindle cell sarcomas (leiomyosarcomas and synovial sarcoma), carcinomas (primary sarcomatoid adrenocortical carcinoma), primary melanoma, and phaeochromocytoma.²³ Metastatic neoplasms, including metastatic sarcomatoid carcinomas, metastatic spindle cell melanomas, and metastatic sarcomas, are other morphologic mimics of aggressive variants of SFT.^16,24 Although CD34 and S100 expression is observed in both schwannoma and SFT, the characteristic Antoni A and Antoni B areas along with STAT6 negativity confirms the diagnosis of a schwannoma and excludes SFT.²⁹ Smooth muscle neoplasms, such as leiomyoma and leiomyosarcoma, may be differentiated from SFT by a myogenic marker-positive, CD34-negative, STAT6-negative immunoprofile. Perineurioma, another rare benign spindle cell tumor, a close morphologic and IHC mimic of SFT, exhibits storiform architecture of spindle cells and CD34 and EMA expression. STAT6 expression and the characteristic SFT defining molecular alteration, however, have not been described in perineurioma.³⁰ At times, diffuse CD34 expression in a monophasic synovial sarcoma (SS) creates a diagnostic problem with a malignant SFT. The absence of STAT6 staining in SS aids in the diagnosis. The characteristic immunoprofile of an adrenocortical carcinoma (melan-A positive/SF1 positive/inhibin positive/CK positive/calretinin positive/CD34 negative/STAT6 negative) distinguishes SFT from an adrenal cortical carcinoma (ACC).³¹ Similarly, the absence of CK staining and STAT6 expression argues against a metastatic carcinoma with spindle cell/sarcomatoid features. Focal spindle cell features may be observed in medullary neoplasms, such as pheochromocytoma, creating diagnostic confusion with an SFT; however, STAT6 negativity confirms a pheochromocytoma. Variable degrees of melanocytic marker positivity differentiate SFT from a melanocytic neoplasm.

The differential diagnoses entertained when dealing with an adrenal round cell or epithelioid SFT include the Ewing family of tumors, Wilms tumor, desmoplastic small round cell tumor, neuroblastoma, small cell carcinoma, hematolymphoid neoplasms, SS, BCOR-CCNB3–associated round cell sarcoma, undifferentiated round cell sarcoma with CIC-DUX4 fusion, Merkel cell carcinoma, and embryonal rhabdomyosarcoma. Typically, the immunopanel used to clinch a specific diagnosis in the above-mentioned setting includes neither CD34 nor STAT6, and the neoplasms are typically STAT6 negative.³² Of note, variable CD34 expression may be observed in SS and hematolymphoid neoplasms. Another interesting and uncommon morphology is the papillary SFT reported by Yao et al.⁹ Most of the cases (9/12 [75%]) summarized in the study occurred in the meninges, and only 1 was reported in the adrenal gland. The diagnosis was clinched by the STAT6 immunostain positivity in all tumors described in this series. This finding highlights the diagnostic difficulty of exclusive histomorphology and the importance of specific immunostains. Other morphologic variants are fat-forming SFT, giant cell-rich variant, malignant SFT, and dedifferentiated SFT (p53 positive).² Nevertheless, these are not described in the SFTs of the adrenal gland, including our cohort.

The present cohort highlighted the diagnostic utility of STAT6 in SFT, and STAT6 has an edge over CD34 in this neoplasm. All tumors in our cohorts showed positive STAT6 immunostain; however, 2 of 9 tumors were negative. This finding identifies STAT6 to be a more accurate and consistent marker for SFTs independent of the site in which they occur. Other markers that show variable and random expression in SFT are CD99, BCL2, and EMA, as exemplified by the tumors in our case series and the prior documented cases. Nevertheless, their positivity in other soft tissue tumors is quite common. STAT6 positivity is consistent with the demonstration of NAB2ex4::STAT6ex2 in the same tumor, defining it as the surrogate marker for the fusion protein.³³ Nonetheless, for diagnostic purposes, in the cases where STAT6 immunostain is negative, the molecular analysis is an additional advantage in detecting SFT.

Although the CD34-positive/CD99-positive phenotype is characteristic of SFT and aids in differentiating this tumor from other mesenchymal mimics, there is a subset of SFTs in which the expression of these 2 markers may be decreased or absent. These tumors are considered dedifferentiated and show necrosis, cystic degeneration, more frequent mitosis; they also tend to lose the typical staining pattern of conventional SFT, with CD34 being lost in 50% of cases.^7,34 In general, across the anatomic locations and in a diagnostically challenging scenario, STAT6 staining is extremely helpful. In multiple studies carried out to assess the efficacy of STAT6 as a specific marker for SFT, it has shown high sensitivity and specificity (close to 100%).^{4,7,8,10,11,24,29,33} It could be lost in dedifferentiated tumors, however. In the limited studies of STAT6 expression in dedifferentiated SFT, high-grade areas have been shown to exhibit heterogeneous staining patterns with STAT6 compared with the conventional and malignant areas.^35,36 There was no such occurrence in our group of adrenal SFTs. A study reported 6 cases of NAB2::STAT6 fusion–negative SFTs with positive STAT6 immunostain, suggesting the existence of fusion variants that are not included in the reverse transcription polymerase chain reaction (RT-PCR) assay.³⁷ As NAB2 and STAT6 are in close proximity on chromosome 12q, detection of their fusion is difficult by conventional cytogenetic methods, and the diversity of breakpoints occurring in both exons and introns makes PCR-based detection of fusion variants difficult without multiplexed sequencing assays. In such scenarios, STAT6 IHC is a sensitive and specific surrogate for all fusions and has immense utility in arriving at a correct diagnosis.^4,7,37 Furthermore, dedifferentiated SFTs may tend to exhibit heterogeneity in STAT6 staining and may be completely negative in a small core biopsy specimen, rendering the diagnosis of SFT difficult. In such instances, molecular assays have great utility. Therefore, IHC and molecular assays supplement each other in the diagnosis.

Demicco et al in 2012⁴ proposed the risk stratification model used to assess the metastatic potential of an SFT. That model included 3 variables—namely, patient age, tumor size, and mitotic activity—with the incorporation of tumor necrosis later. In the modified risk stratification system, which includes necrosis as the fourth variable, Demicco et al⁷ concluded that low-risk cases (66%) do not metastasize even at 10 years of follow-up; the intermediate-risk category (24% cases) carried a 10% risk of metastasis at 10 years; and the high-risk category, which constituted the fewest cases, had a 73% risk of metastasis at 5 years. Although none of the present cohort showed metastasis, we tried to classify them into various risk categories to ascertain the likelihood of metastasis. In the present study, low-risk cases constitute 88.9% (8/9) of the cohort; the remaining 1 case was of intermediate risk. Eight of 12 prior reports on adrenal carcinoma could be designated into a risk class based on the available data. Low-, intermediate-, and high-risk groups constituted 50%, 37.5%, and 12.5% of the other cases, respectively. These findings in adrenal SFTs are in line with the study by Demicco et al,⁷ where low-risk strata had the maximum number of patients. Furthermore, Demicco et al in 2018³⁸ added TERT mutation as the possible prognostic factor in the risk assessment for metastasis and recurrence of primary SFTs. They found, however, that the mutation status is associated with the aggressiveness of the tumor but could not be established as a consistent predictor of overall survival and long-term outcome of the disease. The mutation is present in 29% of the SFTs, thereby emphasizing its usefulness in the stratification of intermediate-risk tumors and their behavior. High mitotic activity (>4/10 HPFs or 2 mm²), TERT promoter, and TP53 mutations correlate better with aggressiveness.³⁹ The STAT6 IHC and the detection of the NAB2::STAT6 fusion protein are used to clinch the diagnosis of SFT, but there is no correlation with the risk stratification for metastasis and recurrence, which depend on the 4 criteria described earlier. Neither the IHC nor the molecular pathology altered the risk stratification for propensity to metastasize and recur in cases of adrenal SFT in the present series.

The prognosis for SFTs is favorable, and surgical resection suffices despite aggressive histomorphology.³⁸ Uncertain prognostication in terms of late recurrence and metastasis,⁵ however, warrants the conception of a risk stratification system for this deceptive tumor type. The inability to determine the fusion gene through sequencing is acknowledged as the limitation of our study that might have helped us determine further potential fusion partners. The IHC and molecular findings did not correlate with the risk stratification and were reserved for diagnostic purposes.

The follow-up duration available was comparatively less in our cohort. Therefore, regardless of the parameters used to assess the biologic behavior, the follow-up of our 9 cases was just too short (<2.5 years) to have any meaningful clinical significance.

Adrenal SFTs are extremely rare neoplasms with a favorable disease course. STAT6 IHC is the most specific and sensitive immunohistochemical marker for the diagnosis of adrenal SFT and can be used as a surrogate for the NAB2::STAT6 fusion, particularly in a resource-limited setting. Also, the gene fusion may be negative in a subset of tumors, where STAT6 IHC aids in the diagnosis. Furthermore, risk stratification provides an insight into the tumor behavior following surgical resection. Long-term follow-up is mandated because recurrences have been documented in SFT cases over the years. Further discovery of mutations involved in the carcinogenesis and prognostication of SFT pertaining to adrenal glands could encourage the formulation of novel chemotherapeutic treatment protocols.

This work has been presented as an abstract at the United States & Canadian Academy of Pathology Annual Meeting; March 2022; Los Angeles, CA.

REFERENCES

Author notes