Low-grade Mucoepidermoid Carcinoma Research Articles

Mucoepidermoid Carcinoma of the Thyroglossal Duct: Two Rare Entities in a Unique Case Report.

Mucoepidermoid Carcinoma (MEC) of the thyroid represents less than 0.5% of all thyroid neoplasms. Thyroglossal duct cyst carcinoma is a rare condition with only approximately 300 cases reported. A 34-year-old pregnant woman at 37 weeks gestation presented to an endocrinological center for primary autoimmune hypothyroidism. The thyroid ultrasound revealed a pseudonodular pattern. The patient was followed up after two years. She reported a full-term delivery without complications. A new thyroid ultrasound was performed, showing a cystic lesion in the median suprathyroid area, measuring 6 x 9 x 10 mm, not previously reported. After 4 months, the suprathyroid cystic lesion was confirmed by thyroid ultrasound, measuring 6 x 11 x 12 mm. The patient was referred for fine-needle aspiration cytology. Cytological examination showed lymphocytes, red blood cells, and some epithelial aggregates with large cytoplasm and nuclear polymetrism with oxyphilic aspects. The patient underwent the Sistrunk procedure for the suprathyroid lesion. The histological examination revealed lymphocytic thyroiditis in heterotopic thyroid tissue with solid cell nest, epidermoid epithelium, and mucus-secreting cells suggestive of low-grade mucoepidermoid carcinoma. The immunohistochemistry study was positive, exhibiting thyroid transcription factor 1 and cytokeratin-19. No positivity was observed for thyroglobulin, calcitonin, galectin-3, and Hector Battifora mesothelial antigen 1. The recent follow-up examination, 13 months after the surgery, has been found negative for disease recurrence. This is the first case of an MEC occurring within a thyroglossal duct. Considering the age of the patient, the histological diagnosis, and the absence of thyroid nodules and metastasis, we decided on the Sistrunk procedure without total thyroidectomy.

Bronchial Mucous Gland Adenoma of the Lung: A Rare Tumor: A Case Report

Bronchial mucous gland adenoma (BMGA) is a very uncommon, benign lung tumor, defined as a proliferation of seromucous glands in the bronchial lamina propria. The majority arises within the main, lobar, or segmental bronchi. The diagnosis depends on tissue biopsy. Mucous gland adenoma needs to be distinguished from low-grade malignant tumors of the bronchus, most considerably, invasive mucinous adenocarcinoma and low-grade mucoepidermoid carcinoma. We report the case of a 40-year-old man who was operated for a broncho-pulmonary tumor whose anatomopathological study revealed an adenoma of the bronchial mucous glands. Through this case, we present the histological characteristics that led to the diagnosis and discuss the different differential diagnoses.

Comments on "Mucoepidermoid carcinoma of the bronchus: a rare early diagnosis".

Dear Editor, An article published in 2020 in this journal reported a rare case of a young medical student presenting with low grade mucoepidermoid carcinoma (MEC) of central airway. Curative sleeve resection was done, with negative margins and no evidence of lymph nodal involvement. The current letter presents a 3-year follow up of the same individual and a short review of the evidence available for post-resection monitoring in such patients.

Critical Appraisal of Histologic Grading for Mucoepidermoid Carcinoma of Salivary Gland: Is an Objective Prognostic 2-tiered Grading System Possible?

Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We aimed to identify prognostic histologic factors and to evaluate grading schemes in this retrospective study of 262 resected primary head and neck MECs. The rate of nodal metastasis was 8.4%. Large tumor size, tumor fibrosis, infiltrative border, lymphovascular invasion, perineural invasion, atypical mitosis, mitotic index (MI) ≥4/2mm 2 (4/10HPFs), necrosis, and pT4 stage were associated with increased risk of nodal metastasis. The 5-year recurrence-free survival (RFS) was 95%. Significant prognostic factors for RFS included infiltrative border, tumor-associated lymphoid stroma, architectural patterns (macrocystic, microcystic, and noncystic), anaplasia, atypical mitosis, MI, necrosis, lymphovascular invasion, margin, pT stage, and tumor size. Nuclear anaplasia, high mitotic rate, and ≥25% microcystic component were significant independent prognostic factors on multivariate survival analysis. There was no significant difference between low-grade (LG) and intermediate-grade (IG) MECs in terms of risk of nodal metastasis and outcomes using all 4 known grading systems. Rather, high-grade MEC was consistently associated with an increased risk of nodal metastasis at presentation and decreased RFS and distant metastasis-free survival (DMFS) compared with the LG/IG MECs. We therefore recommend simplifying MEC grading to a 2-tiered grading scheme using MI and/or tumor necrosis. Using a 2-tiered grading, high-grade histology independently predict RFS, and is associated with a 25% risk of nodal metastasis, a 5-year RFS of 76%, and a 5-year DMFS of 76%, whereas LG MEC has a nodal metastasis rate of 7.0%, 5-year RFS of 97% and 5-year DMFS of 99%.

Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland

It has long been known that high-grade mucoepidermoid carcinoma (MEC) has a poor prognosis, but the detailed molecular and biological mechanisms underlying this are not fully understood. In the present study, the pattern of chymase-positive mast cells, as well as chymase gene expression, in high-grade MEC was compared to that of low-grade and intermediate-grade MEC by using 44 resected tumor samples of MEC of the parotid gland. Chymase expression, as well as chymase-positive mast cells, was found to be markedly increased in high-grade MEC. Significant increases in PCNA-positive cells and VEGF gene expression, as well as lymphangiogenesis, were also confirmed in high-grade MEC. Chymase substrates, such as the latent transforming growth factor-beta (TGF-β) 1 and pro-matrix metalloproteinase (MMP)-9, were also detected immunohistologically in high-grade MEC. These findings suggested that the increased chymase activity may increase proliferative activity, as well as metastasis in the malignant condition, and the inhibition of chymase may be a strategy to improve the poor prognosis of high-grade MEC of the parotid gland.

A CASE REPORT OF MUCOEPIDERMOID CARCINOMA: A RARE PRESENTATION AT SUBMANDIBULAR SALIVARY GLAND

Introduction: Mucoepidermoid Carcinoma (MEC) is the most common malignant salivary gland neoplasm, representing 10 to 15% of all salivary neoplasms. Case Report: Ÿ A rare case of mucoepidermoid carcinoma of the left submandibular gland in a 36-year-old female patient who presented to ENT OPD with a painless mass in the left submandibular region. Ÿ histopathological examination conrmed the diagnosis of low-grade mucoepidermoid carcinoma of the submandibular gland. Ÿ Not all diagnostic features are found on ne needle aspiration, especially in low-grade lesions. Ÿ The diagnosis may be missed or confused with other benign and malignant lesions. Ÿ Treated by total excision of the left submandibular gland and no recurrence seen within 3 months of follow-up.

下口唇に生じた粘表皮癌例

Minor salivary gland tumors are rarely encountered head and neck tumors. These tumors are more often malignant than neoplasms of the major salivary glands. In this article, we report a patient with mucoepidermoid carcinoma of the lower lip. The patient was a 50-year-old woman who presented with the chief complaint of pain in the lower lip. On examination, a small nodule was palpable on the right side of the lower lip, with tenderness. MRI did not reveal any lesion. Therefore, we performed surgery under local anesthesia for diagnosis and treatment. The nodule was confirmed by palpation and removed with the surrounding tissue. Histopathology revealed the diagnosis of low-grade mucoepidermoid carcinoma, and the resection margins were negative. Although the incidence of minor salivary gland tumors is low, they must be included in the differential diagnosis of nodular lesions of the lower lip, as the incidence of malignant transformation of these tumors is relatively high.

Synchronous nasal mass: a wolf in sheep’s disguise

Aim: To highlight the possibility of synchronous benign and malignant nasal masses. Schneiderian papilloma, also known as inverted papilloma, despite being a common benign epithelial sinonasal tumour, remains a conundrum to otorhinolaryngologists due to its locally aggressive nature, tendency to recur as well as potential of malignant transformation. A synchronous nasal lesion adds on to the complexity of patient management. Case presentation: Herein, we are reporting an unusual case of synchronous lesions: sinonasal inverted papilloma and low-grade mucoepidermoid carcinoma. Initial biopsy of the sinonasal mass revealed inverted papilloma. However, histopathological examination post endoscopic medial maxillectomy revealed evidence of both inverted papilloma and low-grade mucoepidermoid carcinoma. Conclusion: We want to highlight that seemingly benign sinonasal inverted papillomas ought to be taken seriously considering the possibility of a synchronous malignant nasal mass, as in our case.

Salivary Duct Cyst with Sialolithiasis in Upper Lip: A Rare Entity

AbstractSalivary duct cyst (SDC) is a true salivary gland pathology that rarely occurs in the upper lip. The proposed rarity of SDC is around 0.39% of all the salivary cystic lesions. It usually arises in the lower lip or the floor of the mouth and is prevalent in the sixth/eight decade of life. We report a case of 76-year-old male patient with a chief complaint of an abnormal growth of the upper lip. The growth had increased in size from the last two months. Clinically it was a well circumscribed, solitary, nodular, painless, mobile, noncompressible, soft growth. Excisional biopsy was performed. Histology revealed a SDC and sialolithiasis in the upper lip. This article aims to include SDC in the differential diagnosis of lesions in the upper lip. Their clinical and histopathology features mimic salivary gland pathology such as mucocele, pleomorphic adenoma, basal cell adenoma, low-grade mucoepidermoid carcinoma.

Endoscopic resection of bronchial mucoepidermoid carcinoma in a young adult man: A case report and review of literature

Primary tracheobronchial mucoepidermoid carcinoma (MEC), derived from salivary mucus glands, is an uncommon neoplasm in adults. At present, surgery is still the preferred treatment for adult bronchial MEC, although it may cause significant trauma and loss of lung function. Here, we report a patient with endobronchial MEC who received the interventional bronchoscopic therapy to remove the neoplasm and no recurrence occurred during follow-up. A 28-year-old man was admitted to our unit with mild hemoptysis for 3 d. Physical examination did not show any abnormal signs, and the serological indexes were all in the normal range. Chest computed tomography (CT) indicated an intraluminal nodule in the bronchus intermedius with homogeneous density and a well-defined margin. Upon fiberoptic bronchoscopy, an endobronchial pedunculated polypoid was discovered without submucosal involvement. As the neoplasm was confined to the bronchus, interventional bronchoscopy was performed to remove the mass by high-frequency electric knife and laser resection. Tissue was sampled and histopathological examination confirmed the diagnosis of low-grade MEC. As the proliferation index was low, no further treatment was given. During 2 years of follow-up, the patient's condition was good and no relapse was discovered under fluorescence bronchoscopy or CT scan. Interventional bronchoscopy can be considered for treatment of low-grade bronchial MEC, with few complications and preserved lung function.

Salivary papillary cystic low-grade mucoepidermoid carcinoma and cystadenoma: a comparison of clinicopathological and genetic features

Objective: To study the clinicopathologic and genetic features of papillary cystic low-grade mucoepidermoid carcinoma (LG-MEC) and cystadenoma. Methods: A retrospective review was performed on salivary gland tumor patients with papillary cystic architecture who presented to department of oral pathology, Peking University School and Hospital of Stomatology between January 2010 and June 2022. Among this cohort, there were 17 males and 17 females with a range age of 23-82 years [(55.6±14.6) years]. Diagnosis was confirmed by histological, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Finally, 15 papillary cystic LG-MEC and 19 cystadenoma patients were included in the present study. All patients were followed clinically and radiologically, and the duration of follow-up ranged from 1 to 141 months. Results: All neoplasms showed papillary proliferation with multilocular or giant cystic tumors. Papillary cystic LG-MEC was characterized by epidermoid cells, intermediate cell and mucous cells with multiple lining-layers. Papillary cystic LG-MEC had mild cellular atypia and a pushing infiltration. Cystadenoma was characterized by cuboidal, columnar and ciliated pseudostratified columnar lining epithelium. Squamous metaplasia, mucinous metaplasia and acidophilic degeneration could also be observed focally in cystadenoma. For IHC staining, papillary cystic LG-MEC showed diffusely and strongly positive for mucin 4 (MUC4) (15/15) and mucin 5 Subtype AC (MUC5AC) (4/15) in the epidermoid cells, intermediate cell and mucous cells. The epidermoid cells and intermediate cells were diffusely positive for p40 and p63. The Ki-67 index was about 10%-15% in LG-MEC. As a contrast, p40 (17/19) and p63 (14/15) were only detected in the basal cells of cystadenoma. Cystadenoma showed focal MUC5AC (4/19)expression and MUC4 (19/19)diffuse expression. In addition, the Ki-67 index was 5%-10% in cystadenoma. The MAML2 gene translocation was detected in 11 LG-MEC patients, but none in cystadenoma. Conclusions: The differential diagnosis points between papillary cystic LG-MEC and cystadenoma included the specific epidermoid cells, intermediate cells and mucus cells in LG-MEC, cell atypia, the pushing-infiltration pattern, diffuse expression of p40 and p63 in the lining epithelium, and a MAML2 gene rearrangement. The molecular test of MAML2 should be recommended to reduce missed LG-MEC diagnoses.

Warthin Tumor - Diagnostic Dilemma- Case Report

Warthin Tumor is also known as Papillary Cystadenoma lymphomatosum, is a fairly common tumor. Cytologically, it simulates many other lesions of salivary glands like chronic sialadenitis, low grade mucoepidermoid carcinoma, acinic cell carcinoma, squamous cell carcinoma, oncocytic carcinoma, lymphoepithelial cyst etc which poses a diagnostic dilemma.

A RIDDLE WRAPPED IN A MYSTERY: MUCOEPIDERMOID CARCINOMA (MEC) FOUND DURING EVALUATION OF PERSISTENT LUNG COLLAPSE

A RIDDLE WRAPPED IN A MYSTERY: MUCOEPIDERMOID CARCINOMA (MEC) FOUND DURING EVALUATION OF PERSISTENT LUNG COLLAPSE

Mammary Analogue Secretory Carcinoma of Parotid - a Pathological Mystery.

Salivary gland neoplasms account for 3-6% of head and neck tumours. 70-80% of parotid tumours are benign in histopathology. FNAC has an overall accuracy of 95% in diagnosis of parotid neoplasms. However, the remaining 5% still pose a histopathological mystery which may require a surgical excision of the parotid. We report a case of a 42 year-old-man with a history of parotid swelling and a FNAC report which showed a possibility of a low-grade mucoepidermoid carcinoma or a ductal adenocarcinoma. Final histopathological diagnosis after surgical excision revealed a new pathological entity in mammary analogue secretory carcinoma of parotid.

18년 뒤 재발한 비인두의 점액표피양암종 1예

Mucoepidermoid carcinoma is a common cancer in the salivary glands, but very rarely in the nasopharynx. Since nasopharyngeal tumors often complain of only non-specific symptoms such as nasal obstruction or epistaxis, they are often discovered at an advanced stage, so proper diagnosis and treatment are important. We experienced a 68-year-old women who complained of nasal obstruction. She had a history of surgical removal of a low-grade mucoepidermoid carcinoma in the nasopharynx 18 years ago. On endoscopic examination, a mass was found in the same location of nasopharynx. It was confirmed that it had recurred as a high grade mucoepidermoid carcinoma, and was completely removed by an endoscopic approach. We report a case of recurred mucoepidermoid carcinoma of nasopharynx 18 years after surgery with a literature review.

OW GRADE MUCOEPIDERMOID CARCINOMA IN PALATE

A 65-year-old male patient presented for dental care reporting a "lump in the roof of the mouth for years." On physical examination, a papular lesion was observed in the transition region of the hard and soft palate, on the left side, measuring about 5 × 5 mm, with a similar color to the mucosa and floating consistency on palpation. In the anamnesis, the patient reported more than a 5-year evolution time, painless, no harmful habits, and no systemic changes. There was no radiographic alteration. Thus, the diagnostic hypotheses were aimed at benign/proliferative lesions. An excisional biopsy was performed, and the histopathologic report showed low-grade mucoepidermoid carcinoma (MEC). As treatment, an excisional biopsy was considered, and the patient continues to be monitored by the head and neck surgeon. MEC is an aggressive malignant lesion and should be considered in conjunction with the diagnosis of benign/proliferative lesions of the salivary glands, especially on the palate.

Secretory Carcinoma of the Salivary Glands


 
 
 
 A 29-year-old woman presented with a 3-month history of an enlarging right infra-auricular mass. A fine needle aspiration biopsy revealed a cellular aspirate consistent with a salivary gland neoplasm of uncertain malignant potential (The Milan System for Reporting Salivary Gland Cytopathology Category IV-B). She subsequently underwent superficial parotidectomy, revealing a poorly circumscribed tumor measuring 1.8 x 1.2 x 1.0 cm in the superficial lobe of the parotid gland.
 
 
 
 
 On microscopic examination, the tumor was composed of microcystic, follicular, and tubular structures lined by mildly atypical, hobnailed cells with abundant granular to foamy, pale, eosinophilic cytoplasm, and round to oval, vesicular nuclei containing finely granular chromatin and prominent, centrally located nucleoli. (Figure 1) Intraluminal secretions were present within the microcysts and tubules, staining positive for Periodic Acid Schiff (PAS) that was resistant to diastase digestion. (Figure 2) Immunohistochemistry studies for S100, SOX10, and Mammaglobin showed strong, diffuse positivity in the tumor cells, in contrast to the absence of staining observed for DOG1. (Figure 3) Given the described morphological and immunological findings, a diagnosis of secretory carcinoma was rendered. No foci of high-grade transformation, i.e., areas with a solid growth pattern, nuclear anaplasia, increased mitoses, or necrosis, were noted.
 
 
 
 
 Secretory Carcinoma or Mammary Analogue Secretory Carcinoma (MASC) is a recently described low grade salivary gland malignancy that bears a morphologic resemblance to mammary secretory carcinoma, harboring a similar chromosomal translocation, t(12;15) (p13;q25), that most commonly produces a fusion of the ETV6 and NTRK3 genes.1-5 Occurring in adults (mean patient age of 46.5 years) without a predilection for either sex, these tumors most commonly arise in the parotid gland.1,2
 
 
 
 
 Historically, secretory carcinomas have been diagnosed as either acinic cell carcinoma – due to the close morphological similarity of having a microcystic or follicular growth pattern or adenocarcinoma that is not otherwise specified. Aside from the characteristic ETV6-NTRK3 gene fusion, secretory carcinomas may be differentiated from acinic cell carcinoma by having no basophilic zymogen cytoplasmic granules in the tumor cells in contrast to the latter, and the diffuse expression of S100 and Mammaglobin as well as the absence of DOG1 expression in secretory carcinoma on immunohistochemistry. 1,2 Low grade mucoepidermoid carcinoma may also present as a possible morphological differential diagnosis. Immunohistochemistry studies for p63 (expressed in epidermoid cells of mucoepidermoid carcinoma), as well as S100 and Mammaglobin (no expression expected in mucoepidermoid carcinoma) may be sufficient to differentiate between the two entities. On a cytogenetic level, most low grade mucoepidermoid carcinomas harbor a chromosomal translocation, t(11:19), that results in a characteristic CRTC1-MAML2 gene fusion in contrast to the ETV6-NTRK3 fusion seen in secretory carcinoma.1-3 The light microscopic features of this particular case however are sufficiently distinct from a mucoepidermoid carcinoma that we felt that this entity could be excluded based on routine H&E morphology. It is granted however, that molecular testing, e.g., in-situ hybridization to demonstrate characteristic chromosomal aberrations, may prove valuable in morphologically ambiguous cases. Its unavailability in the local setting is thus a limitation.
 
 
 
 
 
 
 
 
 Secretory carcinomas are mostly reported to be indolent though are associated with lymph node metastasis in up to 25% of cases. Like other low grade salivary gland carcinomas, locoregional recurrence and distant metastasis have been documented in rare cases. However, high clinical grade and high-grade morphological transformation have been reported and are associated with adverse outcomes.1,2,4,5 The patient tolerated the surgical procedure well, and had no evidence of disease eight months after the operation. Reporting this fairly uncommon entity is encouraged to further expand our understanding of its biology and natural history.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Low-Grade Invasive Triple Negative Breast Carcinoma

Triple-negative breast carcinomas (TNBCs) are defined as estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative breast carcinomas and are composed of a heterogeneous group of breast carcinomas with most of them having aggressive behavior and poor prognosis. However, some TNBC cases are low grade with indolent clinical outcome and low risk of metastasis to other organs or regional lymph nodes. Low-grade TNBCs include low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade invasive (ductal or lobular) carcinoma with apocrine differentiation, classic adenoid cystic carcinoma, secretory carcinoma, tall cell carcinoma with reversed polarity, acinic cell carcinoma, and low-grade mucoepidermoid carcinoma. This review aims to summarize the clinicopathological correlation and the molecular features of low-grade special TNBC subtypes.

Mucoepidermoid carcinoma: Analysis of 76 cytologic cases and correlation with histologic grade

Mucoepidermoid carcinoma (MEC) is the most common salivary gland (SG) malignancy. In this study, the author undertook analysis of a large collection of MEC cytologic cases. Cytopathology files were searched for MEC cases with histopathologic confirmation. Fine-needle aspiration (FNA) smears used standard technique. Seventy-six cases (63 patients [M:F=1:1; age range, 23-87 years; mean age, 58 years]) met inclusion criteria. Aspirates were primary (54 [71%]), metastatic (18 [24%]), and locally recurrent (4 [5%]). FNA sites included parotid gland (49 [64%]), regional lymph nodes (11 [14%]), submandibular gland (5 [7%]), inner canthus of eye (2 [3%]), and lung (2 [3%]); and single specimens from palate, jaw, shoulder, paranasal sinus, floor of mouth, ear canal, and effusion. Cytologic diagnoses included MEC (30 cases [39%]), suspicious for MEC (16 [21%]), non-MEC carcinoma (9 [12%]), suspicious for malignancy (SM) (2 [3%], malignant (M) (1 [1%]), SG and/or suspicious SG neoplasm (7 [8%]), atypical (3 [5%]), nonneoplastic (5 [6%]), nondiagnostic (2 [3%]), and benign SG neoplasm (1 [1%]). A total of 26% of low-grade (LG) cases were diagnosed as malignant in contrast to 87% malignant in high-grade (HG) cases. Cytomorphology depended on tumor grade. LG MEC contained intra- and/or extra-cellular mucin and more uniform cell and/or nuclear morphology, whereas cytologic atypia, anisonucleosis, and keratotic cells were more typical of HG tumors. A malignant (M) or suspicious for malignancy (SM) cytologic interpretation was made in 76% of mucoepidermoid carcinoma (MEC) cases. In contrast to high-grade MEC (97% identified as M/SM), only 59% of low-grade (LG) MEC cases were interpreted as such, illustrating the continued diagnostic challenge posed by LG MEC using fine-needle aspiration biopsy.

Oncocytic variant of mucoepidermoid carcinoma – A report of two cases and review of histopathology, immunohistochemistry, and molecular profiling

Oncocytic changes have been described in approximately 10% of salivary gland tumors. It has been associated with a variety of benign and malignant tumors such as Warthin tumor, cystadenoma, pleomorphic adenoma, polymorphous adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma (MEC), among others. MEC is the most common salivary gland malignancy and exhibits various histological patterns. Oncocytic MEC (OMEC) is a rare variant characterized by a predominant oncocytic cell population. Herein we present two challenging cases of OMECs. The first case was of a 63-year-old male with a mixed cystic to solid lesion in the superficial parotid gland. The lesion had ill-defined margins and no internal calcifications. The initial radiographic impression was that of a pleomorphic adenoma. The second case was that of a 67-year-old male with a parotid gland mass. Histologic examination of both cases showed extensive areas of oncocytic differentiation with scattered sebaceous and mucous cells. Immunohistochemical analysis showed the neoplastic population to be positive for AE1/AE3, p63, and mucicarmine in the first case and p40 and mucicarmine in the second case. A diagnosis of low-grade mucoepidermoid carcinoma, oncocytic variant, was rendered in both cases. The first case was further analyzed for <i>MAML2/CRTC1</i> rearrangement by FISH and found to be positive. Differentiating between salivary gland neoplasms with oncocytic changes can be challenging due to significant histologic overlap. Ancillary studies to include immunostains and molecular testing can be useful in establishing a definitive diagnosis.