Mesenchymal Elements Research Articles

Fibro-Adipose Vascular Anomaly (FAVA): Not Another Vascular Anagram.

Background. Fibro-adipose vascular anomaly (FAVA) is a rare benign mesenchymal lesion. Characterized primarily by intramuscular vascular malformation with secondary overgrowth of other mesenchymal elements, particularly fibro-adipose tissue, the condition is sometimes complicated by nonspecific clinical and imaging features, causing diagnostic dilemma. Herein, we attempted to outline and correlate the clinical characteristics, imaging findings, and histopathological features of this unusual entity. Method. The study design was retrospective in nature. Computerized database of our institute was searched for tumors, and archived slides were reviewed. Pertinent clinical data including imaging findings and treatment details were also recovered for correlation. Result. Among total of 24 patients identified, mean age was approximately 16 years, with the presence of nearly equal gender distribution. Pain along with swelling was most common symptoms with the presence of movement limitation, in few. Most lesions were long-standing and anatomically confined to lower limb with no side predilection. Using imaging, the majority of the lesions were identified as vascular anomaly or venous malformation, with FAVA being a differential diagnosis in few lesions. However, in a couple of patients, likelihood of mesenchymal tumors was also suggested, radiologically. On histology, the lesions showed the presence of clustered back to back, abnormal thin-walled, variably dilated, blood-filled sac-like vessels amid skeletal muscle bundles, along with extensive fibro-adipose tissue and variably atrophic skeletal muscle bundles, at the periphery, diagnostic of FAVA. Conclusion. Owing to the presence of overlapping clinical and imaging features, FAVA is often misdiagnosed, causing dilemma in clinical management. Clinical, radiological, and histopathological correlation is thereby warranted for clinching the correct diagnosis.

Paratesticular rhabdomyosarcoma: a rare case report from Syria.

In this paper, the authors report a case of a 6-year-old child who presented to the clinic with a painless mass in the right side of the scrotum. The mass was misdiagnosed and had evolved rapidly over 2 weeks. The mass measured 16×32mm on ultrasound, and therefore, an orchiectomy was performed. The histological examination of the excised tissue confirmed the diagnosis of paratesticular RMS. Paratesticular RMS mainly presented as a painless mass in the scrotum. It was a very metastatic lesion that required an immediate management. However, a lot of cases of paratesticular RMS misdiagnosed at first time, which worsens the overall prognosis. Eventually, paratesticular RMS should be always taken into consideration when a scrotal mass is suspected. Due to its extremely serious metastatic potential, this condition requires early diagnosis and management. The treatment is currently well codified combining surgery, chemotherapy, and radiotherapy.

Macrodystrophia lipomatosa of the right foot: a case report and treatment

Macrodystrophia lipomatosa (MDL) is a rare congenital disorder characterized by localized gigantism of one or several digits. It mayinvolve the entire limb due to progressive overgrowth of all mesenchymal elements with an excessive increase in the fibro-adiposetissues. It occurs most commonly in the lower limbs. It comes to clinical attention for cosmetic reasons, mechanical problems secondaryto degenerative joint disease, or the development of neurovascular compression. We report a case of MDL of the right foot withdifficulty walking and wearing footwear. With a complete radio-clinical workup and history review, a provisional diagnosis of MDL wasmade, confirmed by histopathology and during surgery. Level of Evidence V; Therapeutic Studies; Expert Opinion.

Insight into the molecular pathogenesis of odontogenic tumours

Odontogenic tumors, derived from epithelial, ectomesenchymal, and/or mesenchymal elements of the tooth-forming apparatus, constitute a heterogeneous group of lesions, including hamartomas, benign and malignant neoplasms with metastatic capabilities. This review provides a comprehensive overview of the molecular events in the pathogenesis of odontogenic tumors. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

Teratocarcinosarcoma of the head and neck: Clinicopathologic review of a rare entity.

Teratocarcinosarcoma is a rare, highly aggressive malignancy of the head and neck, characterized by multiphenotypic and triphasic growth of epithelial, mesenchymal, and primitive neuroepithelial elements. Owing to its rarity and morphological heterogeneity, as well as the lack of experience with this neoplasm, teratocarcinosarcoma is often misdiagnosed, particularly in small biopsy samples when only some of the elements are identified, thus leading to delayed management. Aggressive clinical behavior and poor survival outcomes, necessitate an accurate diagnosis and appropriate treatment. This review describes the main demographic and clinicopathological features of teratocarcinosarcoma, with an emphasis on the recent advances that have attempted to identify the molecular signature of this neoplasm.

A160 A SARCOMATOID CARCINOMA OF THE COMMON BILE DUCT PRESENTING AS PAINLESS JAUNDICE AND EXTRAHEPATIC BILIARY OBSTRUCTION

Abstract Background Sarcomatoid carcinomas are extremely rare tumors made of epithelial and mesenchymal elements. They have been found in various organs, but presence in the common bile duct (CBD) has only been reported a handful of times. Insight regarding the clinical history, histopathology, treatment, and prognosis is limited. The majority of CBD sarcomatoid carcinomas have occurred in elderly women, including this case. Surgical resection is the mainstay of treatment and the roles for chemotherapy and radiation therapy are undetermined. Prognosis is variable, but generally poor. Purpose Additional information regarding sarcomatoid carcinomas of the CBD will aid in establishing a timely diagnosis and may alter treatment options and prognosis. We aim to add to the limited literature surrounding this rare CBD neoplasm. Method A 71-year-old female presented with painless jaundice, decreased appetite, and weight loss. Initial investigations showed an alkaline phosphatase (ALP) of 3075 U/L, aspartate transaminase (AST) of 507 U/L, alanine aminotransferase (ALT) of 298 U/L, total bilirubin of 325.5 µmol/L, and direct bilirubin of 254.1 µmol/L. Initial computed tomography (CT) scan done showed marked intra- and extrahepatic biliary ductal dilation with appropriate tapering and the presence of a distal CBD hyperdensity. Tissue biopsy obtained by endoscopic retrograde cholangiopancreatography (ERCP) was suspicious for a malignant peripheral nerve sheath tumor. The differential also included synovial sarcoma and sarcomatoid mesothelioma. Result(s) After multidisciplinary discussion involving hepatobiliary surgery, medical oncology, and radiation oncology, pancreaticoduodenectomy was performed; there was no role for neoadjuvant/adjuvant chemotherapy/radiation therapy. Final pathology revealed a well circumscribed mass with a narrow attachment to the posterior CBD, measuring 5.6 x 3.2 x 2.8 cm. Immunohistochemistry showed mixed differentiation with sarcomatoid, squamous, and glandular components, consistent with a sarcomatoid carcinoma. H3K27me3 expression was lost in neoplastic cells. Immunostaining showed strong expression of vimentin and weak expression of CD34, calretinin, CK5 and EMA. Post-operative course was complicated by pancreaticojejunal leak, surgical wound infection, myocardial injury, and esophageal stricturing. 14-weeks post-pancreaticoduodenectomy the patient was found to have C.difficile infection and a perforated viscus, exact location of which was not visible on imaging. Emergent laparotomy revealed a gastroduodenal leak and diffuse small bowel ischemia. The patient passed away shortly after emergent surgery. Conclusion(s) This case illustrates a rare presentation of sarcomatoid carcinoma within the CBD and highlights some of the diagnostic challenges, limited management strategies, complications, and potential poor prognosis of the disease. Further research is required to guide diagnosis and management, and ultimately improve patient outcomes. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Malignant cutaneous mixed tumour arising on the upper back: a case report

Background: Malignant adnexal tumours are a heterogenous group of rare neoplasms comprising <0.002% of skin cancers.1 Cutaneous mixed tumour (chondroid syringoma) is an adnexal neoplasm with epithelial and mesenchymal elements. Its malignant counterpart has both a malignant epithelial component and areas of chondroid and myxoid differentiation.2 Malignant transformation is rare with limited reports in the literature.

Palatal swelling: Pleomorphic adenoma – A case report

Pleomorphic adenoma is a most common benign neoplasm of salivary glands that has the epithelial as well as the mesenchymal elements. The World Health Organization in 1972 defined pleomorphic adenoma as a “well-defined tumor characterized by its pleomorphic or mixed appearance.” There is intermixing of the clearly identified epithelial components with mucoid, myxoid, and chondroid components. Pleomorphic adenoma most commonly arises in the parotid or submandibular gland and infrequently occurs in minor salivary glands and presents as intraoral swellings on the palate or lip. The tumor shows a malignant transformation rate of about 9%, and a high recurrence rate has been reported. This case report highlights the clinical, radiological, and histopathological presentation of pleomorphic adenoma.

Metaplastic Breast Carcinoma: A Case Series with Three Different Presentations

Metaplastic Breast Carcinoma (MBC) is one among the rare types of breast carcinoma. MBC was recognised as a separate entity by World Health Organisation (WHO) in 2020. According to WHO, metaplastic carcinoma is classified into six types based on the histology which includes: low grade adenosquamous carcinoma; fibromatosis like metaplastic carcinoma; squamous cell carcinoma; spindle cell carcinoma; carcinoma with heterologous mesenchymal differentiation; and mixed metaplastic carcinomas. This rare type of tumour shows both epithelial and/or mesenchymal elements within the same lesion. The management of these patients remains an enigma due to the rarity of the tumour and the treatment responses between patients following therapy. In the present case series, five cases of MBC and their follow-up have been described. All patients were females within the age group of 50-65 years. All five patients underwent modified radical mastectomy. Lymph node involvement was noted in one case. Among the five cases, two patients had adenosquamous carcinoma, two patients had metaplastic carcinoma with heterologous mesenchymal differentiation and one patient had mixed metaplastic carcinoma.

Merger and Consolidation-Carcinosarcoma-Uterine Cervix

Carcinosarcoma of uterine cervix is an exceptionally encountered, high grade neoplasm composed of malignant epithelial and mesenchymal elements. Additionally designated as malignant mixed mesodermal tumour, homologous neoplasms of uterine cervix are denominated as carcinosarcoma.

Lipomatosa macrodystrophia: pediatric case report of a congenital anomaly in the lower limb

Background: This report presents the case of a rare, sporadic, and non-hereditary congenital anomaly called macrodystrophia lipomatosa, which manifests as congenital localized gigantism. It is characterized by the proliferation of all the mesenchymal elements of a single digit or multiple digits. This is coupled with an excessive increase of fibro-adipose tissue involving the nerve sheath, muscle, periosteum, and bone marrow. Case Presentation: We present the case of a 1-year-old girl, who had presented to Security Forces Hospital, Riyadh, Saudi Arabia with congenital unilateral enlargement of the left forefoot. The localized enlargement involved the second, third, and fourth toes. A detailed clinical history was recorded and routine radiography and magnetic resonance imaging (MRI) scans were performed, to assess the skeletal structures. Amputation of the hypertrophic tissue followed by surgical reconstruction of the forefoot ensured optimum management of the case. Conclusion: This report is among the few cases of this rare condition, reported from Saudi Arabia. This case report emphasizes and reiterates the significant role of eliciting a detailed patient history, conducting a thorough radiographic examination including MRI scans and planning optimum surgical interventions, for patients of macrodystrophia lipomatosa. The overall treatment plan needs to adequately address the patients&amp;apos; cosmetic and functional disturbances and should mitigate the risk of potential neuro-vascular involvement.

Clinical and pathomorphological aspects of odontogenic tumors.

Odontogenic tumors (OTs) comprise agroup of heterogeneous lesions ranging from hamartomatous or non-neoplastic tissue proliferation to benign or malignant neoplasms with metastatic potential. OTs are derived from epithelial, ectomesenchymal, and/or mesenchymal elements of tooth-forming ("odontogenic") tissues, which show variable clinical and histopathological features. Herein, the authors summarize the World Health Organization (WHO) 2022 classification of OTs and further highlight diagnostic tips and differential clues for the most common OTs. OTs may not be commonly encountered in the daily practice of many pathologists. This makes their diagnosis challenging as there is little practice in understanding the features required for their classification. However, diagnosing the vast majority of these lesions is not difficult provided the following aspects are considered: 1)the general knowledge of tooth development; 2)afew key histological observations; 3)very basic knowledge of the clinical and especially the radiographic features with which they are associated.

Comprehensive Molecular Profiling of Sinonasal Teratocarcinosarcoma Highlights Recurrent SMARCA4 Inactivation and CTNNB1 Mutations.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor defined by intermixed neuroepithelial, mesenchymal, and epithelial elements. While its etiology was historically ambiguous, we recently reported frequent SMARCA4 loss by immunohistochemistry, suggesting that TCS might be related to SMARCA4-deficient sinonasal carcinomas. However, other molecular alterations including CTNNB1 mutation have been reported in TCS, and its full genetic underpinnings are unclear. Here, we performed the first comprehensive molecular analysis of sinonasal TCS to better understand its pathogenesis and classification. We collected 30 TCS including 22 cases from our initial study. Immunohistochemical loss of SMARCA4 was seen in 22 cases (73%), with total loss in 18 cases (60%). β-catenin showed nuclear localization in 14 cases (64%) of the subset tested. We selected 17 TCS for next-generation sequencing with enrichment for partial or intact SMARCA4 immunoexpression. We identified inactivating SMARCA4 mutations in 11 cases (65%) and activating CTNNB1 mutations in 6 cases (35%), including 5 cases with both. Of 5 cases that lacked SMARCA4 or CTNNB1 mutation, 2 harbored other SWI/SNF complex and Wnt pathway alterations, including 1 with SMARCB1 inactivation and 1 with concomitant APC and ARID1A mutations, and 3 had other findings, including DICER1 hotspot mutation. These findings confirm that SMARCA4 inactivation is the dominant genetic event in sinonasal TCS with frequent simultaneous CTNNB1 mutations. They further underscore a possible relationship between TCS and sinonasal carcinomas with neuroendocrine/neuroectodermal differentiation. However, while SMARCA4 and β-catenin immunohistochemistry may help confirm a challenging diagnosis, TCS should not be regarded as a molecularly defined entity.

137P Combining protein and mRNA spatial profiles to identify distinct cell population in metaplastic breast cancer

Metaplastic breast cancer (MpBC) is a heterogeneous disease and is characterized by the differentiation of the neoplastic epithelium into squamous cells and/or mesenchymal elements. MpBC is rare but very aggressive and presents high rates of recurrence, poor survival outcomes, and poor response to current chemotherapies optimized for other breast cancer subtypes. To date, there are no established treatments for MpBCs, due to paucity of clinical trials and near absence of preclinical models for investigation.

Folliculosebaceous Cystic Hamartoma Arising in Miescher-Type Melanocytic Nevi.

Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma consisting of dilated folliculosebaceous units associated with mesenchymal elements. Ansai et al reported that distinctive features of Miescher-type melanocytic nevi (MMCNs) accompanied 4.6% of FSCH; however, there have been no data about how often FSCH features accompany MMCNs. In this study, we used 7829 cases that had been histopathologically diagnosed as MMCNs of the face, neck, and scalp at the Department of Dermatopathology, Nippon Medical School Musashi Kosugi Hospital and observed whether features of FSCH accompanied them. Of the resected MMCNs, 274 of 7829 (3%) were accompanied by features of FSCH. The nose was the most common resection site, followed by the eyebrow area, ear, and cheek. The coexistence rate for the nevi on the nose and features of FSCH was as high as 10%-20%, and its rate increased with age. We found that FSCH appears mostly in seborrheic areas, such as the nose and cheek, which are rich in normal sebaceous glands. This suggests that nevi, especially on and around the nose, may induce FSCH or similar lesions.

Revisiting Metaplastic Carcinoma of Breast: An Emphasis on the Clinico-pathological and Immunohistochemical Variables Analyzed at a Tertiary Cancer Centre in South India.

Background & Objective:Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling with a high proliferation index and a dismal prognosis. Lymph node metastasis is an unusual feature in metaplastic carcinoma. Methods: The present study analyses 30 cases (26 cases of modified radical mastectomy and 4 cases of lumpectomy) of metaplastic carcinoma over 2018-2020 (3 years). Four oncopathologists reviewed routine histopathologic and immunohistochemical-stained slides. The clinical details were collected from the Medical Records Department of the Cancer Institute.Results:A total of 20 (66.67%) cases were patients >50 years of age, 21(70%) out of which were diagnosed as invasive carcinoma, grade 3 according to the Nottingham histological score. Five (16.7%) cases presented with lymph node metastasis. While immunohistochemically 28 (93.3%) cases were triple-negativeCK5/6, P63, EGFR, and Ki-67 (more than 40%) positivity was noted in 25 (83.3%) , 26 (86,7%) , 20 (66.7%), and 25 (83.3%) cases, respectively. Conclusion:Metaplastic carcinoma is characteristically triple-negative breast malignancies (TNBC) exhibiting a high Ki-67 index and a lower rate of lymph node metastasis. CK5/6, p63, and EGFR are pertinent immunohistochemical markers that may aid in diagnosis. However, those markers are non-specific for the disease and morphologic features are always the key to diagnosis of the process.

Association of Vascular Endothelial Growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) with Radiotherapy Response in High-Grade Sarcomas

Background: Sarcoma is a rare malignant aggressive tumor originating from mesenchymal elements. High-grade sarcoma has a poor prognosis. The mortality rate of high-grade sarcomas is 50–75%. Radiotherapy is needed in high-grade sarcoma. Radioresistance in the high-grade sarcoma is still common. Vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) are molecular markers that play a role in radioresistance. This study aimed to analyze the association of VEGF and mTOR with radiotherapy response in high-grade sarcoma. Method: This study was an analytic observational study with a cross-sectional design. The minimum samples based on Lameshow’s formula included 40 selected paraffin-embedded tissue blocks from biopsy high-grade sarcoma, consisting of 20 samples of radioresistance and 20 samples of radiosensitive. Immunohistochemistry staining for VEGF and mTOR were performed on all samples. Statistical analysis used the Chi-Square test. The significance of the data was obtained when p-value &lt;0.05.Result: High immunoexpression of VEGF (OR = 17, p &lt; 0.05) and mTOR in high-grade sarcoma showed a significant association with radiotherapy response (OR = 16, p &lt; 0.05). The stepwise logistic regression analysis revealed that both VEGF and mTOR immunoexpression influenced radiotherapy response simultaneously. Conclusion: In this study, which used a minimum sample, it can be concluded that the higher VEGF and mTOR immunoexpression showed the higher radioresistance in high-grade sarcoma.

Pulmonary Blastoma in a Young Adult

Pulmonary blastoma is a rare but aggressive malignancy of the lung comprising epithelial and mesenchymal elements that resemble fetal lung tissue. This report described a case of an 18-year-old male who presented with cough and weight loss for a month. Computed tomography (CT) of the thorax revealed a large mass with mixed solid and cystic lesions on the right side of chest along with pleural effusion and mediastinal lymphadenopathy. Massive debulking was performed followed by chemotherapy. A biphasic pulmonary blastoma was diagnosed on histopathology.

CASE REPORT: PULMONARY HAMARTOMA IN PATIENT WITH BREAST CANCER

TYPE: Case Report TOPIC: Cardiothoracic Surgery INTRODUCTION: Pulmonary hamartoma accounts 77% of benign lung tumors and 4% of solitary pulmonary nodules. It is more common in male adults. It is rare benign lung tumors and are composed of an abnormal mixture of epithelial and mesenchymal elements. It usually presents as single, round nodules with distinct boundaries and mostly asymptomatic. Metastasis was differential diagnosis. Enclulation was done through mini-thoracotomy. Histopathological examination confirmed the diagnosis. CASE PRESENTATION: 47-years female referred from Oncology Department with two pulmonary nodules. She had bilateral mastectomy 3-years ago. The patient had a history of hormonal therapy and chemotherapy, as well as of adjuvant radiotherapy. Chest CT revealed two pulmonary nodules (3 × 2.5 cm). Pulmonary metastasis was differential diagnosis and biopsy indicated for confirmation. Enucleation was performed through mini-thoracotomy. The excised nodules were firm, and non-capsulated. The patient recovered well and discharged on 3rd POD. DISCUSSION: The incidence of pulmonary hamartoma was 0.25%. It is more common in adult males,and discovered accidentally . [4] It is the third most common cause of SPN. [5] Surgical resection is a definitive diagnosis, and with low morbidity and mortality rate. [1] Conservative lung sparing surgery is indicted. [4] Pulmonary nodules in breast cancer patients should be treated after pathological confirmation. The most common “symptoms” is fear, as these tumors can similar to cancer when found, especially on imaging. [5] CONCLUSIONS: Pulmonary hamartomas present as PSN. Sparing lung surgery is recommended for accurate diagnosis and treatment. DISCLOSURE: Nothing to declare. KEYWORD: Hamartoma, Solitary Pulmonary Nodule, Lung Cancer, Breast Cancer, Metastasis.

CD90 Marks a Mesenchymal Program in Human Thymic Epithelial Cells In Vitro and In Vivo.

Thymic epithelium is critical for the structural integrity of the thymus and for T cell development. Within the fully formed thymus, large numbers of hematopoietic cells shape the thymic epithelium into a scaffold-like structure which bears little similarity to classical epithelial layers, such as those observed in the skin, intestine or pancreas. Here, we show that human thymic epithelial cells (TECs) possess an epithelial identity that also incorporates the expression of mesenchymal cell associated genes, whose expression levels vary between medullary and cortical TECs (m/cTECs). Using pluripotent stem cell (PSC) differentiation systems, we identified a unique population of cells that co-expressed the master TEC transcription factor FOXN1, as well as the epithelial associated marker EPCAM and the mesenchymal associated gene CD90. Using the same serum free culture conditions, we also observed co-expression of EPCAM and CD90 on cultured TECs derived from neonatal human thymus in vitro. Single cell RNA-sequencing revealed these cultured TECs possessed an immature mTEC phenotype and expressed epithelial and mesenchymal associated genes, such as EPCAM, CLDN4, CD90 and COL1A1. Importantly, flow cytometry and single cell RNA-sequencing analysis further confirmed the presence of an EPCAM+CD90+ population in the CD45- fraction of neonatal human thymic stromal cells in vivo. Using the human thymus cell atlas, we found that cTECs displayed more pronounced mesenchymal characteristics than mTECs during embryonic development. Collectively, these results suggest human TECs possess a hybrid gene expression program comprising both epithelial and mesenchymal elements, and provide a basis for the further exploration of thymus development from primary tissues and from the in vitro differentiation of PSCs.