Myoid Differentiation Research Articles

A Case Series of Myopericytoma: A Soft Tissue Neoplasm

Myopericytoma (MPC) is a rare benign mesenchymal neoplasm with perivascular myoid differentiation that most commonly arises in middle adulthood. The lesion generally involves the subcutaneous soft tissue of the lower extremities. Histologically, it is characterised by concentric perivascular proliferation of spindled myoid cells with bland elongated nuclei associated with blood vessels. The present case series emphasises five cases of MPC in relatively younger-aged female patients. Fine Needle Aspiration Cytology (FNAC) was inconclusive in all five patients. Histopathological examination showed perivascular concentric proliferation of myoid tumour cells, which were ovoid, spindled, or round cells with abundant eosinophilic cytoplasm, and no nuclear atypia, hyperchromasia, or necrosis. Immunohistochemistry (IHC) was positive for Smooth Muscle Actin (SMA). Although MPC can be diagnosed through histopathological examination, IHC is required for confirmation.

PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth

We show that Polycomb Repressive Complex-2 (PRC2) components EED and EZH2 maintain neural identity in cerebellar granule neuron progenitors (CGNPs) and SHH-driven medulloblastoma, a cancer of CGNPs. Proliferating CGNPs and medulloblastoma cells inherit neural fate commitment through epigenetic mechanisms. The PRC2 is an epigenetic regulator that has been proposed as a therapeutic target in medulloblastoma. To define PRC2 function in cerebellar development and medulloblastoma, we conditionally deleted PRC2 components Eed or Ezh2 in CGNPs and analyzed medulloblastomas induced in Eed-deleted and Ezh2-deleted CGNPs by expressing SmoM2, an oncogenic allele of Smo. Eed deletion destabilized the PRC2, depleting EED and EZH2 proteins, while Ezh2 deletion did not deplete EED. Eed-deleted cerebella were hypoplastic, with reduced proliferation, increased apoptosis, and inappropriate muscle-like differentiation. Ezh2-deleted cerebella showed similar, milder phenotypes, with fewer muscle-like cells and without reduced growth. Eed-deleted and Ezh2-deleted medulloblastomas both demonstrated myoid differentiation and progressed more rapidly than PRC2-intact controls. The PRC2 thus maintains neural commitment in CGNPs and medulloblastoma, but is not required for SHH medulloblastoma progression. Our data define a role for the PRC2 in preventing inappropriate, non-neural fates during postnatal neurogenesis, and caution that targeting the PRC2 in SHH medulloblastoma may not produce durable therapeutic effects.

Interstitial Cells of Cajal-Origin, Distribution and Relationship with Gastrointestinal Tumors.

The interstitial cells of Cajal (ICC) represent a particular network formed by some peculiar cells that were first described by the great neuroanatomist, S. Ramon y Cajal. Nowadays, the ICC have become a fascinating topic for scientists, arousing their curiosity; as a result, there is a vast number of published articles related to the ICC. Today, everybody widely accepts that the ICC represent the pacemaker of the gastrointestinal tract and are highly probable to be the origin cells for gastrointestinal tumors (GISTs). Recently, Cajal-like cells (ICLC) were described, which are found in different organs but with an as yet unknown physiological role that needs further study. New information regarding intestinal development indicates that the ICC (fibroblast-like and muscle-like) and intestinal muscle cells have the same common embryonic cells, thereby presenting the same cellular ultrastructure. Nowadays, there is a vast quantity of information that proves the connection of the ICC and GISTs. Both of them are known to present c-kit expression and the same ultrastructural cell features, which includes minimal myoid differentiation that is noticed in GISTs, therefore, supporting the hypothesis that GISTs are ICC-related tumors. In this review, we have tried to highlight the origin and distribution of Cajal interstitial cells based on their ultrastructural features as well as their relationship with gastrointestinal stromal tumors.

Dermatofibrosarcoma protuberans of the face: A clinicopathologic and molecular study of 34 cases.

Dermatofibrosarcoma protuberans (DFSP) is one of the most common dermal sarcomas, but facial DFSP is rare. The clinicopathological characteristics of 34 facial DFSPs were reviewed. Additional immunostaining (CD34) and PDGFB/COL1A1-PDGFB fluorescence in situ hybridization (FISH) detection were performed. Patients were aged from 24 to 64 years (mean 42.9 years), with a male-to-female ratio of 4.7: 1. Morphologically, classic DFSP (25/34, 73.5%), pigmented DFSP (2/34, 5.9%), DFSP with myoid differentiation (1/34, 2.9%) and fibrosarcomatous DFSP (FS-DFSP) (6/34, 17.6%) were found. Moreover, myxoid degeneration was observed in three FS-DFSP cases (3/6, 50.0%). All 29 cases that underwent CD34 immunohistochemistry exhibited positive staining (100%). Genetically, PDGFB rearrangement/COL1A1-PDGFB fusion was detected in 94.1% (16/17) of patients. Regarding prognosis, the recurrence (83.3% vs. 59.1 %) and metastasis (33.3% vs. 0%) rates were higher in FS-DFSPs than that in ordinary DFSPs. All available surgical margins were positive before DFSPs recurrence. All patients with negative excision or re-excision margins were alive without evidence of disease (mean, 81.8months; median, 81months). Facial DFSP occurs predominantly in males, while FS-DFSPs are more likely to exhibit myxoid degeneration and a worse prognosis. Notably, negative surgical margin status determined a satisfactory prognosis.

Multifocal Myopericytomas

Myopericytoma is a rare soft tissue tumour which orginates from pericytes. Histopathology shows nodular perivascular proliferation of cells with myoid differentiation. Myopericytomatosis and multifocal myopericytomas are the two uncommon variants of this entity. We report an uncommon case of multifocal myopericytomas over the sole.

Potential pathogenetic link between angiomyofibroblastoma and superficial myofibroblastoma in the female lower genital tract based on a novel MTG1-CYP2E1 fusion

Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism.

S2083 A Case of Medication-Induced Black Esophagus

Introduction: Acute esophageal necrosis (AEN), also known as black esophagus, is characterized by diffuse inflammation and necrotic appearance of esophageal mucosa. The pathogenesis has been attributed to a 2-hit hypothesis: a low-flow state creating ischemic injury, followed by an inciting event, such as infection or toxicity. The reported rate of incidence via endoscopy is 0.0125%-0.2%. Here, we describe a case of ischemia and medication-induced AEN in an elderly male. Case Description/Methods: An 83-year-old immunosuppressed male with a past medical history of HTN, insulin-dependent diabetes, CABG, mechanical aortic valve replacement, atrial fibrillation on warfarin, myasthenia gravis (MG) on Cellcept and prednisone, and decompensated cirrhosis with prior duodenal ulcer bleeds who presented with non-bloody emesis and diarrhea. On arrival, he was hemodynamically stable with laboratory results revealing mild AKI and abdominal CT scan showing duodenitis. On the second day, he experienced hematemesis and became progressively lethargic, hypotensive, tachypneic, tachycardic, and febrile. Lab work showed elevated ammonia, lactate, and white cell count. He was intubated for airway protection, resuscitated with IVF, and given broad-spectrum antibiotics, and IV PPI. Repeat abdominal CT scan showed worsening duodenitis without evidence of perforation or abscess. Esophagogastroduodenoscopy (EGD) revealed non-bleeding duodenal ulcers and mucosa with possible ischemic changes involving nearly the entire esophagus (Figure 1). EGD established the diagnosis of AEN, however, biopsy was not performed. Follow-up chest CT showed a moderately diffusely thickened wall of the esophagus without evidence of esophageal perforation. Discussion: Our patient had a host of specific factors for developing AEN. His history of decompensated cirrhosis with recurrent duodenal bleeds predisposed him to develop ischemia, leading to the first hit associated with developing AEN. His history of MG requiring him to take the AEN-associated medication, Cellcept, likely predisposed him to develop toxic injury, leading to the second hit. Due to poor prognosis after declining esophagectomy, the patient was transitioned to comfort care and passed away shortly thereafter.Figure 1.: A. Spindle cell proliferation with myoid differentiation. B. Calcifications arising from the muscularis propria in the upper esophagus on endoscopic ultrasound.

Myoid differentiation in dermatofibrosarcoma protuberans: a rare phenomenon

Myoid differentiation in dermatofibrosarcoma protuberans: a rare phenomenon

Oral myopericytoma: a rare pediatric case report and a review of the literature

BackgroundMyopericytoma is a rare mesenchymal neoplasm with perivascular myoid differentiation that arises most commonly in middle adulthood. The lesion generally involves the subcutaneous tissue of distal extremities. Myopericytoma of the oral cavity is extremely rare. Herein we report a case of oral myopericytoma in a pediatric patient, who was treated via a conservative approach with a follow up of 8 years. The case is followed by a literature review. To our knowledge this is the first documented case of oral myopericytoma affecting a patient of such a young age.Case presentationA 6 years old boy was referred to the maxillofacial surgery department for the evaluation of a solitary growth of the right maxillary buccal and palatal gingiva. Histology and immunohistochemistry confirmed the diagnosis of myopericytoma.ConclusionsOur patient was treated by local excision with no recurrence in 8 years of follow up. Conservative approach should be considered for the treatment oral myopericytoma especially in young patients in tooth bearing areas.

Histomorphological and immunophenotypical spectrum of cutaneous myoepitheliomas: A series of 35 cases.

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.

Cellular Testicular Fibroma of Gonadal Stroma with Extensive Myoid Differentiation: A Mimicker of Testicular Leiomyoma

Fibroma of the testis is a rare benign Sex Cord Stromal Tumour (SCST) of probable gonadal stromal origin, occurring in adult males. Characterised by slow and insidious growth, it is devoid of hormonal association and serum markers. Clinically, it can mimic seminoma and requires histopathological examination for identification. Microscopic characteristics include hypercellular spindle cell areas and hypocellular hyaline plaques. Authors report a case of a 41-year-old male presenting with complaints of lower abdominal pain and dysuria. Ultrasonography (USG) showed enlarged left testis with heterogenous echotexture. With a clinical diagnosis of testicular tumour, orchidectomy was performed. Histology showed a well circumscribed, encapsulated cellular neoplasm comprising of spindle and fusiform cells in fascicles, nodules and bundles. The cells showed fusiform vesicular nuclei and eosinophilic cytoplasm, focal epithelioid cells with grooved nuclei and occasional mitotic figure. Stromal collagen fibres and hyalinisation were noted. Testicular tissue was seen compressed peripherally. The tumour cells demonstrated positive reactivity for Smooth Muscle Actin (SMA), h-Caldesmon and inhibin, negative for S-100 and CD34 (Cluster of Differentiation) on Immunohistochemistry (IHC). Literature review helped in arriving at a diagnosis of cellular Testicular Fibroma (TF) with myoid differentiation. Testicular spindle cell lesions are rare, and comprise of different entities, one of which is TF. Histology and IHC are useful aids in diagnosis. Awareness of the differential diagnosis and the IHC markers can help in arriving at a conclusive diagnosis.

Soft tissue sarcomas: Evaluation by immunohistochemistry

Soft tissue sarcomas represent a histologically heterogenous group of malignant tumors arising from the soft tissue compartments, i.e smooth muscles, skeletal muscles, adipose tissue, blood vessels, connective tissue mesenchyme, neural tissue and other tumors of uncertain histogenesis(1). Soft tissue sarcomas are relatively rare tumors, represent less than 1% of adult malignancies based on data report from American Cancer Society (2). The crude incidence rate in Iraq for soft tissue sarcomas was 219/ 100,000 population during 2014 with male: female ratio of 1.3:1, and highest peak age between 30-34 years (3). The histological subtype and microscopic criteria are two parameters that influence the tumor grade which is the best predictor for aggressiveness. ( 2)
 Objectives:
 A retrospective evaluation of soft tissue sarcomas, using immunohistochemical study of Myosin, Desmin, Smooth muscle Actin (SMA) and Vimentin, aiming to re-evaluate the primary diagnosis and whether IHC assessment in soft tissue sarcoma is mandatory to reach a final interpretation.
 Material and Patients: 
 A total of 50 cases soft tissue sarcomas were reviewed retrospectively from case archives of histopathology department/ Central Public Health Laboratory, for the period (2011-2018). The data for these cases were collected including the age, gender, site of the tumor and the preliminary biopsy report findings. Hematoxylin& Eosin (H&E) stain and IHC staining of unstained sections from formalin-fixed, paraffin-embedded tissue were performed using SMA, Vimentin, Desmin and Myosin.
 Methods: Age and gender distribution of the 50 cases was correlated. The IHC staining performed on 5 microns paraffin sections, applying peroxidase-Antiperoxidase technique and both positive and negative control slides were included for Smooth muscle actin (SMA), clone 1A4, Desmin (clone D33), Myosin (clone 2F12.A9) and Vimentin (Clone V9). The monoclonal antibodies used were from DAKO manufacturer as ready to use monoclonal antibodies while freeze-dried antibodies used for myosin with 1:20 dilution. Negative and positive control slides were used simultaneously. The staining intensity was assessed based on the percentage of positive cells expression of the four IHC monoclonal antibodies. Negative staining reported when no stain seen. Positive (+) means up to 30% of tumor cells with antigen expression. Positive (++) interpretation given when 31-60% of tumor cells show staining reaction, while Positive (+++) interpretation reported when over 60% of tumor cells showing staining reaction.
 Results:
 The staining interpretation of the four monoclonal antibodies were confirmatory for the original diagnosis in 40% of cases, while 60% of the final diagnoses were against the original interpretation. SMA was positive in 38/50 cases (76%). Desmin was positive in 8/50 cases (20%) Vimentin was positive in 42/50 of cases (84%), Myosin was positive in 30/50 of cases (71.4%).
 The current study focus on histological re-evaluation of different types of soft tissue sarcomas (including RMS-with its subtypes), MFH-storiform, pleomorphic and myxoid subtypes), fibrosarcoma, leiomyosarcoma, alveolar soft part sarcoma and synovial sarcoma depending on immunohistochemical study. The original diagnosis have been changed after the immunohistochemistry stain from fibrosarcoma to rhabdomyosarcoma and leiomyosarcoma , Malignant fibrous histiocytoma to rhabdomyosarcoma, alveolar rhabdomyosarcoma to Malignant fibrous histiocytoma, soft tissue sarcoma to rhabdomyosarcoma , pleomorphic MFH to pleomorphic rhabdomyosarcoma. Embryonal and alveolar rhabdomyosarcoma were confirmed by IHC as so. Leiomyosarcoma was confirmed as the same in one case. Embryonal Rhabdomyosarcoma changed to leiomyosarcoma by IHC positivity for desmin. Six cases of MFH were confirmed as malignant fibrous histiocytoma after IHC. Two cases of synovial sarcoma were re-evaluated as rhabdomyosarcoma. Vimentin revealed 100% positivity in 10 cases and regarded as a sensitive marker for mesenchymal tissue but it is not specific for certain types of sarcomas. The presence of desmin diffusely throughout a tumor is an indication of myoid differentiation and the presence of either SMA or desmin focally should not necessarily be equated with myoid lineage but rather with myofibroblastic lineage, which go in the same direction with Hirofumi N. et al. (1998).(4)
 Conclusions: The co-expression of SMA and Desmin helped in the diagnosis of leiomyosarcoma (LMS). Myosin expression was helpful in the diagnosis of rhabdomyosarcoma (RMS) and alveolar soft part sarcoma (ASPS). Smooth muscle actin (SMA) and vimentin were not specific for the diagnosis of malignant fibrous histiocytoma (MFH). High grade spindle cell sarcoma express SMA only without myosin or desmin can be categorized as pleomorphic myogenic sarcoma. By applying immunohistochemical markers, 60% of soft tissue sarcomas were different from the preliminary diagnosis while 40% of cases were supportive of the original H&E diagnosis.

Expression of TdT in Myoepithelial Cells: Investigation in Breasts, Sweat Glands, and Salivary Lesions Emphasizing the Never-Documented Immunohistochemical Findings.

Background. The expression of terminal deoxynucleotidyl transferase (TdT) in myoepithelial cells (MECs) within the breast was recently incidentally observed in our routine practice. This study aimed to elucidate the expression of TdT in MECs. Methods. TdT immunostaining was performed on 180 mammary, 89 cutaneous, and 94 salivary tissues or lesions. Other myoepithelial markers, including P63, calponin, and SMA as well as double staining for TdT and calponin, were also evaluated in some cases. Selected lesions with basal or myoid differentiation were also included in the investigation. Results. MECs were positive for TdT in mammary lesions that contained MECs (132/135) but negative when they did not contain MECs (45/45). MECs in sweat glands (24/30) and their neoplastic counterparts, including those in hidradenoma papilliferum (2/9), spiradenoma (6/6), and cutaneous mixed tumor (9/9), showed weak to moderate TdT positivity. MECs were variably immunolabeled for TdT in salivary or salivary gland-type tumors with myoepithelial differentiation (pleomorphic adenoma, 24/25; basal cell adenoma, 6/7; adenoid cystic carcinoma, 7/7; Warthin tumor, 0/6; mucoepidermoid carcinoma, 0/8; acinic cell carcinoma, 0/4), but MECs in normal salivary gland barely stained for TdT (30/32). Conclusions. Our findings indicate that TdT may be eligible as an additional auxiliary immunohistochemical marker as P63, but not a surrogate, to identify the MECs in the breast with limited cross-reactivity, particularly in lesions with a prominent proportion of MECs. Positivity for TdT, along with other relevant markers, in a subset of sweat gland lesions and salivary tumors may contribute to their diagnosis.

Transzygomatic anterior infratemporal fossa approach and high cervical approach for resection of infra temporal fossa and parapharyngeal space solitary fibrous tumours

The infratemporal fossa (ITF) is the region under the floor of the middle fossa giving passage to most major cerebral vessels and cranial nerves.(1) It is closely related to important adjacent regions such as the middle fossa, pterygopalatine fossa, orbit, and nasopharynx.(2) Due to the anatomical complexity in the ITF, surgical removal of the lesions in or around it is still challenging.(3) Since the 1960s, many surgeons have reported various surgical approaches. the preauricular transzygomatic approach via a transcranial route was reported to be used for exposure of the antero-superior portion of the ITF (2,3). Solitary fibrous tumours (SFTs) were first described by Klempere and Rabin in 1931 as spindle-cell tumours originating from the pleura.(4) With the exception of myopericytoma, infantile myofibromatosis and HPC-like lesions of the sinonasal tract showing myoid differentiation, all other HPC like lesions are best considered as subtypes of SFT.(5) Only a few cases of SFT have been described in the literature involving the skull base and parapharyngeal space.(6–8) The purpose of this article is to show anatomical dissections involving this surgical approach and to evaluate our surgical experience using it.

Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior.

Pericytic tumors comprise a histologic continuum of neoplasms with perivascular myoid differentiation, which includes glomus tumors, myopericytoma, myofibroma, and angioleiomyoma. Despite their morphologic overlap, recent data suggest a dichotomy in their genetic signatures, including recurrent NOTCH gene fusions in glomus tumors and PDGFRB mutations in myofibromas and myopericytomas. Moreover, SRF-RELA fusions have been described in a subset of cellular variants of myofibroma and myopericytoma showing myogenic differentiation. Triggered by an index case of an unclassified cellular myoid tumor showing a novel SRF-ICA1L fusion we have investigated our files for cases showing similar histology and screened them using a combined approach of targeted RNA sequencing and fluorescence in situ hybridization. A fusion between SRF exon 4 and ICA1L exon 10 or 11 was identified in a total of 4 spindle cell tumors with similar clinicopathologic features. Clinically, the tumors were deep-seated and originated in the trunk or proximal lower extremity of adult patients (age range: 23 to 55 y). Histologically, the tumors were composed of cellular fascicles of monomorphic eosinophilic spindle cells showing increased mitotic activity, harboring densely hyalinized stroma, often with focal areas of necrosis. All 4 tumors had similar immunoprofiles with positivity for smooth muscle actin, calponin, and smooth muscle myosin heavy chain. Tumors were negative for desmin and caldesmon, markers often seen in SRF-RELA-positive tumors with similar morphology. Follow-up information was available in 3 patients. Two patients had no evidence of disease, 2 and 5 years after surgical resection. One patient, a 35-year-old male patient with a 19 cm deep-seated tumor with brisk mitotic activity (>20 mitoses in 10 HPF), developed lung metastases 7 years after initial diagnosis. In summary, we report a series of 4 cellular myoid tumors with novel SRF-ICA1L gene fusions, characterized by bland spindle cell fascicular growth, expression of specific smooth muscle markers, elevated mitotic activity, marked stromal hyalinization, focal coagulative necrosis, and potential for malignant behavior. Given the morphologic overlap with related cellular myopericytic tumors with SRF-RELA fusions, it is likely that SRF-ICA1L fusions define a similar subset of neoplasms composed of immature smooth muscle cells.

Variability of CD34 Expression in Sinonasal Glomangiopericytoma: A Potential Diagnostic Pitfall.

Sinonasal glomangiopericytoma (GPC) is an uncommon primary sinonasal neoplasm showing a perivascular myoid differentiation. Originally perceived as an intranasal counterpart to soft tissue hemangiopericytomas, initial immunohistochemical reports showed mostly negative to focal weak reactivity for CD34 as useful in separating GPC (almost always benign) from morphologic mimics, mainly solitary fibrous tumor (potentially aggressive). In anecdotally encountering cases of GPC with CD34 reactivity beyond the expected weak/negative immunoprofile, we sought to formally evaluate CD34 staining in 10 cases of GPC from two different vendors in conjunction with a meta-analysis of other GPC series reporting CD34 staining. Ten cases of GPC were retrieved from the authors' pathology archives (left nasal cavity = 7, right nasal cavity = 3; 5 men, 5 women; average age 59.0years with range of 43-77years). Follow-up showed no evidence of disease after complete resection from all 10 cases (average follow-up length of 53.3months, range 6-106months). All 10 GPC cases (100%) showed positivity using CD34 from Leica (QBend10 clone), with most showing moderate to diffuse staining intensity and moderate extent, while only 2 of 10 cases (20%) showed positivity using CD34 from Ventana (QBend10 clone), with both positive cases showing weak staining intensity and focal extent. Literature review of other studies (reporting ≥ 5 GPC cases) found a wide spectrum of CD34 positivity ranging from 0 to 100%; including our GPC cases, CD34 showed a cumulative positivity of 28%. Although negative CD34 reactivity has been historically regarded as prototypic for GPC, in this study we have exposed laboratory variability in CD34 expression and have shown that reliance on expected negative reactivity in GPC can be a clinically relevant diagnostic pitfall. Our findings suggest a panel approach in selecting diagnostic immunostains rather than relying on CD34 alone in the assessment of spindle cell neoplasms in the sinonasal tract with admixed prominent staghorn-like vasculature.

Sinonasal glomangiopericytoma: A clinicopathologic study

Sinonasal glomangiopericytoma (SNGP) is a neoplasm arising in the nasal cavity and paranasal sinuses that shows perivascular myoid differentiation. The diagnosis of SNGP may be diagnostically challenging due to a large number of potential mimics. In the present study, we sought to characterize the histological and molecular features of six cases of SNGP found in prior surgical pathology records over a 15-year period. The average age at diagnosis was 48.5 years (range: 31–78 years), and the male-to-female ratio was 1:1. Imaging studies in all six cases demonstrated avidly enhancing, lobulated soft tissue masses in the nasal cavity, extending into the sinuses and nasopharynx. Histologically, the tumors were unencapsulated and composed of a proliferation of closely packed, bland, and uniform spindle cells growing deep to an intact surface respiratory epithelium. The cells were separated by a distinctive vascular network ranging from capillaries to large vascular spaces. All cases demonstrated strong positivity for smooth muscle actin, cyclin D1, CD99, and β-catenin (100%). Targeted sequencing revealed recurrent CTNNB1 missense mutations in all cases tested. Additionally, TLE1 was positive in all cases which has not been previously reported. No tested cases harbored SS18 translocations. We found that while no single marker resolves immunohistochemical overlap between SNGP and its histologic mimics, an extended immunohistochemical panel that includes β-catenin, cyclin D1, STAT6, smooth muscle actin, pan-cytokeratin cocktails, S100, and SOX10 helps to support the diagnosis of SNGP in diagnostically challenging cases without the need for molecular studies.

β-catenin (CTNNB1) mutation and LEF1 expression in sinonasal glomangiopericytoma (sinonasal-type hemangiopericytoma)

Sinonasal glomangiopericytoma (SN-GPC) is an uncommon mesenchymal tumor with myoid differentiation. Recently, mutations in exon 3 of the gene coding for β-catenin (CTNNB1) and its nuclear expression were discovered in SN-GPC. β-catenin protein is a key regulatory molecule of the canonical Wnt signaling pathway. The expression of β-catenin target proteins is not well characterized in SN-GPC. We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC.

Mediastinal thymolipoma: a rare occurrence with striated myoid cells.

We describe a 49-year-old man who presented to hospital with unstable angina and who underwent emergency coronary artery bypass grafting. During the surgical procedure, an incidental anterior mediastinal mass was discovered. Histological examination of this mediastinal mass revealed a thymolipoma containing numerous polygonal, striated myoid cells that were immunoreactive for desmin, muscle-specific actin and myoglobin. Electron microscopy demonstrated numerous Z band structures confirming myoid differentiation. Even though the appearance of myoid cells in thymolipoma may be alarming, this tumor should be recognized as a benign entity. Thymolipomas containing striated myoid cells should be differentiated from more ominous thymic neoplasms, including teratomas and thymic liposarcomas. To our knowledge, this is only the third reported case of thymolipoma containing striated myoid cells.

Myofibroblastic, fibroblastic and myoid lesions of the breast

Myofibroblastic, fibroblastic and/or myoid lesions are rare in the breast but comprise the majority of mammary mesenchymal spindle cell lesions. Whereas most have similar features to their counterparts at extramammary sites, pseudoangiomatous stromal hyperplasia is considered a breast-specific myofibroblastic proliferation on the same spectrum as myofibroblastoma. Other lesions with myofibroblastic/fibroblastic differentiation include fibromatosis and nodular fasciitis, as well as more aggressive tumors such as the rarely reported myofibrosarcoma, inflammatory myofibroblastic tumor and fibrosarcoma. Lesions with myoid differentiation include benign leiomyoma, myoid hamartoma and leiomyomatous myofibroblastoma, but primary leiomyosarcoma and rhabdomyosarcoma may also rarely arise in the breast. Furthermore, fibroepithelial lesions and metaplastic carcinomas can demonstrate myoid metaplasia. Diagnosis can be challenging, particularly on core biopsy, but benign lesions with or without recurrence potential must be distinguished from more aggressive tumors, especially metaplastic carcinoma and phyllodes tumors. This article will review lesions with myofibroblastic, fibroblastic and myoid differentiation in the breast, with special emphasis on differential diagnosis.