Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements.

AIMS: The formal pathogenesis of salivary carcinosarcoma (SCS) remained unclear, both with respect to the hypothetical development from either preexisting pleomorphic adenoma (PA) or de novo and the clonal relationship between highly heterogeneous carcinomatous and sarcomatous components. METHODS AND RESULTS: We performed clinicopathological and molecular (targeted RNA sequencing) analyses on a large series of 16 cases and combined this with a comprehensive literature search (111 cases). Extensive sampling (average 11.6 blocks), combined with immunohistochemistry and molecular studies (PA-specific translocations including PLAG1 or HMGA2 proven in 6/16 cases), enabled the morphogenetic identification of PA in 15/16 cases (93.8%), by far surpassing a reported rate of 49.6%. Furthermore, we demonstrated a multistep (intraductal/intracapsular/extracapsular) adenoma-carcinoma-sarcoma-progression, based on two alternative histogenetic pathways (intraductal, 56.3%, versus myoepithelial pathway, 37.5%). Thereby, early intracapsular stages are identical to conventional carcinoma ex PA, while later extracapsular stages are dominated by secondary, frequently heterologous sarcomatous transformation with often large tumour size (>60 mm). CONCLUSION: Our findings strongly indicate that SCS (almost) always develops from PA, with a complex multistep adenoma-carcinoma-sarcoma-sequence, based on two alternative histogenetic pathways. The findings from this novel approach strongly suggest that SCS pathogenetically is a rare (3-6%), unique, and aggressive variant of carcinoma ex PA with secondary sarcomatous overgrowth. In analogy to changes of terminology in other organs, the term "sarcomatoid carcinoma ex PA with/without heterologous elements" might be more appropriate.

Cutaneous pleomorphic adenoma of the periocular region - a case series.

Mixed tumour of the skin is a rare entity also known as chondroid syringoma and pleomorphic adenoma. These usually present as slow-growing skin nodules with a smooth surface, clear boundaries, and no ulceration. Case series exist describing pleomorphic adenomas in the periocular region including the lids and orbit, separate to the more familiar lacrimal gland pleomorphic adenoma. These may arise from accessory or ectopic lacrimal gland tissue but in the eyelids are more likely to arise from sweat glands in the skin. Histopathological analysis of these lesions is important to identify complete excision, minimising recurrences and in identifying rare but potential malignant transformation. We describe the clinical features and outcomes in three cases of pleomorphic adenoma with two at the medial canthus (including one recurrence) and one in the brow region.

Corticomedullary mixed tumour resembling a small adrenal gland-involvement of cancer stem cells: case report.

BACKGROUND: Adrenal corticomedullary mixed tumours are very rare. Its mechanism is rarely reported. Here we report the first case of a corticomedullary mixed tumour resembling a "small adrenal gland" with distinct arrangement of the cortical and medullary layers. We further hypothesize regarding the tumorigenic mechanism of this tumour. CASE PRESENTATION: A 58-year man had been diagnosed with diabetes and hypertension for 3 years. His 24-h urine vanillylmandelic acid (VMA) levels were slightly elevated. An abnormal circadian cortisol rhythm was noted, and his cortisol levels were not suppressed by dexamethasone. Abdominal computed tomography (CT) revealed a right adrenal gland lesion (diameter, 30 × 38 mm), while an enhanced CT showed enhancement and hypervascularization. The tumour was positive for adrenocorticotropic hormone, chromogranin A (CGA), and steroidogenic factor-1 (SF-1) on the tumour surface. Acetaldehyde dehydrogenase 1(ALDH1), CD44, CD133, Nestin, Nerve growth factor receptor (NGFR), and Sex determining region y-box 9(SOX9) staining were positive. Although administration of medications for diabetes and hypertension was stopped until surgery was performed, the blood sugar level and blood pressure were maintained after surgery. CONCLUSIONS: This is the first report about a possible mechanism by which cancer stem cells induce adrenal corticomedullary tumours.

Keloid of Pinna Revealed a Chondroid Syringoma in Disguise.

Cutaneous mixed tumor or chondroid syringoma is a rare benign, skin appendageal tumor prevalent in areas of the head and neck. It represents the cutaneous counterpart of the pleomorphic adenoma of salivary glands. Its clinical presentation often misguides the clinician to underdiagnose it as a reactive lesion. We report the case of a 94-year-old male admitted for excision of cutaneous carcinoma concurrently with a chondroid syringoma of the pinna provisionally misdiagnosed as a keloid.

Ameloblastic Fibro-odontoma - A Case Report of Two Uncommon Cases.

Rationale: Ameloblastic fibro-odontoma (AFO) is a rare mixed odontogenic tumour with a preferential location in the posterior mandible and with a variety of radiological aspects. We report two clinical cases of AFO in two rare locations and with unusual radiological aspects. Patient Concerns: The first patient is a 37-year-old female with an asymptomatic intraoral swelling located in the anterior mandibular. The second patient is a 16-year-old girl with a chief complaint of missing maxillary canine. Diagnosis: Both cases were diagnosed with AFO. Treatment: For the first patient, a biopsy was performed, and for the second one, the lesion was surgically excised. Outcomes: The first patient is under regular surveillance and the other was followed up for one year without any evidence of recurrences. Take-away Lessons: Despite many efforts, the nature, histology and therapy of these lesions remain very confusing.

"The correlation between histopathological pattern and surgical treatment for palatal pleomorphic adenoma. Can we choose a more conservative approach?"

Pleomorphic adenoma (PA) is the most prevalent benign salivary gland tumor. Although rare, among the minor salivary glands, palatal PA exhibits the highest incidence. Unlike other benign tumors, PA infiltrates the surrounding tissues, posing challenges for complete removal through conservative measures. Surgeons often resort to aggressive surgical procedures involving resection of adjacent tissue to ensure clear margins and prevent recurrence. This study aims to analyze diverse histological characteristics of palatal PA, seeking statistical correlations for early prediction of tumor aggressiveness. The goal is to facilitate the preservation of the periosteum during surgical resection and attain conservative surgical margins. A retrospective histopathological investigation encompassed 18 patients diagnosed with palatal PA who underwent surgical treatment at Hadassah Medical Centre, Jerusalem, Israel. Evaluated parameters included tumor size, pseudocapsule thickness, tumor-periosteum distance, and the presence of pseudopodia and satellite nodules indicating tumor penetration. Statistical significance was set at P < 0.05. Tumors of varying sizes, whether large or small, lack consistent features. Neither tumor size, pseudocapsule thickness, nor tumor-periosteum distance displayed correlations with tumor penetration features. Palatal PA exhibits varied histological attributes impacting surgical technique. The absence of correlations among these attributes impedes early prediction of tumor aggressiveness, casting doubt on periosteum preservation. The periosteum is sufficiently robust to contain the tumor and should be excised. There is no data to support either ostectomy or a through-and-through surgical resection as part of the treatment.

Cutaneous Mixed Tumour: A Rare Presentation of a Scrotal Lump Mimicking an Accessory Testis.

Cutaneous mixed tumour (CMT), also known as chondroid syringoma (CS), is a rare benign tumour composed of epithelial, myoepithelial, and mesenchymal components with an incidence of less than 0.01% of primary skin tumours. It is more common in males and typically presents as a painless slow-growing firm mass in the subcutis of the head and neck region. Genital regions are very rarely involved. We present the case of a 50-year-old male with a 10-year history of an asymptomatic gradually enlarging mass in the upper scrotum. A surgical excision was performed. Microscopic examination showed features of CMT. This case highlights the diagnostic challenges associated with scrotal CMT and surgical management of these lesions. Additionally, we endorse the recommended terminology of CMT used by the fifth edition of WHO Classification of Skin Tumours (2023).

Benign Chondroid Syringoma on Chin: A Case Report and Literature Review.

Chondroid syringoma is a cutaneous adnexal tumor originating from sweat glands origin. It is rare in occurrence and usually benign, having an incidence of 0.01 to 0.098%. As these tumors are uncommon, their diagnosis is missed many times and are misdiagnosed. Hence in any case of facial skin swelling increasing slowly in size, this entity should be kept in mind as one of the possibilities and differential diagnosis. Histopathological examination of the excision biopsy gives the definitive confirmatory diagnosis. Surgically excising the swelling locally along with a surrounding normal tissue cuff is the standard treatment given which prevents recurrence. Hereby we present a 35-year-old case of facial chondroid syringoma having a focal component of eccrine hidrocystoma, keratinous cyst as well as syringocystadenoma papilliferum on the chin that was clinically suspected to be an epidermoid cyst or mucocele.

A rare osteolytic lesion in the mandible: A diagnostic dilemma.

Odontogenic myxofibroma is a benign tumour that is rarely encountered in any bone other than jaws. It accounts for only 3-11% of all odontogenic tumours. The pathogenesis of these tumours is still controversial and may arise from myxomatous degeneration or fibrous stroma or from the mesenchymal portion of the tooth germ. Clinically, they are slow-growing and can cause gradual expansion of the cortical plates, loosening, displacement of teeth, and rarely root resorption. Biologically, the tumour is locally aggressive with a high recurrence rate, which warrants extensive surgical treatment. Here, we present a case of central odontogenic myxofibroma in a 45-year-old female resulting in the extensive involvement of the mandible within a month.

Intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma: A case report.

BACKGROUND: The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors. This is, to the best of our knowledge, the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature. CASE SUMMARY: A 61-year-old woman presented to the emergency department for evaluation of painless jaundice. Contrast-enhanced computed tomography (CT) of the abdomen and chest showed a periampullary tumor mass measuring 15 mm × 12 mm × 14 mm, with no evidence of locoregional and distant metastases, for which she underwent pancreatoduodenectomy. Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with high-grade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%. No positive lymph nodes were identified. Her postoperative course was uneventful. Postoperatively, she remained under close surveillance. Multiple liver metastases were observed on follow-up CT 8 mo after the surgery, so systemic therapy with cisplatin and etoposide was initiated. CONCLUSION: The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown. Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy, close patient surveillance is advised after radical resection of the primary tumor.

Mixed tumour of the skin of the lower lip: A case report and review of the literature.

Mixed tumour of the skin or chondroid syringoma (CS) is a rare and mostly benign neoplasm of the sweat glands. Although CS is frequently located on varied parts of the head and neck region, the lower lip is a rarely reported site. The present report describes a case of CS of the lower lip in a 58-year-old male as an expository case to further emphasise the need for proper diagnosis, appropriate treatment and prognostic evaluation. The patient presented with a round, non-tender, slightly hard and mobile mass beneath the mucocutaneous junction of his left lateral side of the lower lip. Radiology revealed a mass measuring 11x11x7 mm3 in size at a depth of ~2 mm. Furthermore, magnetic resonance T1- and T2-weighted images showed slightly low and high signal intensities, respectively. A provisional diagnosis of benign tumour of the lower lip was made, and surgical excision biopsy taken under local anaesthesia, while considering the patient's cosmetic appearance. Histopathology demonstrated features akin to apocrine gland, chondroid and myxoid stroma consistent with the diagnosis of benign CS. No evidence of recurrence or satellites were recorded after a follow-up of nearly 2 years. Although rare, a high index of suspicion for CS among other cutaneous adnexal tumours of the lower lip is necessary. In addition, interprofessional collaboration in the management of such oral tumours could enhance patient satisfaction amid prevailing intraoral and aesthetic concerns.

Pleomorphic adenoma of hard palate: a case report.

Pleomorphic adenoma is a benign mixed tumor, which is composed of myoepithelial and epithelial cells. A fibrous capsule separates these cells from the surrounding tissues. Pleomorphic adenoma is the most common salivary gland tumour accounting for 40-70% of all major and minor salivary gland tumours. It is also the commonest minor salivary gland benign tumours accounting for 70% of all tumours. Hard palate is the commonest site followed by upper lip, buccal mucosa, tongue, floor of mouth, retromolar trigone. This case report discusses a case of pleomorphic adenoma of hard palate in an old man after complete excision of the tumour, which was confirmed by a biopsy specimen.

Understanding of tumourigenesis in canine mammary tumours based on cancer stem cell research.

Mammary tumours occur frequently in female dogs, where such tumours exhibit complexity when examined histologically. These tumours are composed not only of proliferative luminal epithelial cells, but also of myoepithelial cells and/or mesenchymal cells with cartilage and osseous tissues in a solitary mass. The origin of this complexed histogenesis remains speculative, but cancer stem cells (CSCs) are likely involved. CSCs possess self-renewing capacity, differentiation potential, high tumourigenicity in immunodeficient mice, and resistance to chemotherapy and radiation. These cells are at the apex of a hierarchy in cancer tissues and are involved in tumour initiation, recurrence, and metastasis. For these reasons, understanding the properties of CSCs is of paramount importance. Analysis of the characteristics of CSCs may contribute to the elucidation of the histogenesis underlying canine mammary tumours, formulation of novel CSC-targeted therapeutic strategies, and development of biomarkers for early diagnostic and prognostic applications. Here, we review research on CSCs in canine mammary tumours, focusing on: (1) identification and properties of CSCs; (2) hypotheses regarding hierarchal structures in simple type, complex type and mixed tumours of the canine mammary gland; and (3) current and prospective studies of CSC metabolism.

Mixed adenoneuroendocrine carcinoma (MANEC) of the ampulla of Vater in a Chinese patient: A case report.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour of the gastrointestinal tract with both epithelial and neuroendocrine components. We describe a case of a 57-year-old man who presented with yellow sclera and dark urine. Contrast-enhanced computed tomography (CT) showed enlargement of the intra and extrahepatic bile ducts and a neoplastic lesion at the end of the common bile duct which was indistinguishable from the adjacent head of the pancreas and duodenum. A pancreaticoduodenectomy was performed and histopathological examination of resected samples showed that tumour was a complex lesion with adenocarcinoma and neuroendocrine components positive for neuroendocrine markers (chromogranin A and synaptophysin) with a Ki-67 labelling index of 40%. The patient was diagnosed with MANEC in the ampulla of Vater with a neuroendocrine carcinoma component of approximately 70%. Ampullary MANECs are highly aggressive tumours with a high risk for distant metastases and a poor prognosis. Therefore, establishing a standard therapeutic strategy is crucial.

Malignant Chondroid Syringoma: A Report of Two Cases with a Sarcomatous Mesenchymal Component.

Malignant chondroid syringoma (MCS; malignant mixed tumour) is a rare neoplasm typically arising on the extremities and trunk. We are report 2 unique cases of MCS, one occurring on the scalp of a 78-year-old man and the other on the trunk of a 72-year-old woman. Both tumours harboured malignant epithelial and malignant mesenchymal components. The latter was represented by liposarcoma in the first case. The malignant components of the second tumour comprised spindle cell squamous cell carcinoma (SCC) and osteosarcoma. Origin from a pre-existing benign chondroid syringoma was clearly evident in both neoplasms. The presence of heterologous malignant mesenchymal components, however, is hitherto unreported in the context of MCS, while a spindle cell SCC component is exceptionally rare. The 2 cases presented herein highlight an expanded morphological spectrum of MCS, with resultant blurring of the boundaries between MCS and cutaneous carcinosarcoma.

An Uncommon Occurrence of Pleomorphic Adenoma in the Submandibular Salivary Gland: A Case Report.

BACKGROUND: Pleomorphic adenoma is a salivary gland tumour and mostly found in the parotid gland and quite uncommon in the submandibular gland. Pleomorphic tumours are a mixed tumour (benign mixed tumour) consisted of epithelium, myoepithelium, and mesenchyme and made of a view component variation of it. CASE REPORT: We reported a fifty-three years old man with pleomorphic adenoma that has been complaining swelling on the left neck for the last twenty years and treated with surgical excision. Computed tomography of the neck showed soft tissue tumour in the left submandibular. CONCLUSIONS: The best management for pleomorphic adenoma is surgery, the tumour tissue must be removed as a whole because the remaining parts of a tumour can easily become recurrent or turn into a malignant tumour.

[Sarcomatoid carcinoma of larynx. A histological challenge?] / Carcinoma sarcomatoide de laringe. ¿Un reto histológico?

INTRODUCTION: Sarcomatoid carcinoma can occur in any part of the body; in the head and neck it occurs most frequently in the major salivary glands, with only about 1% of cases found in the larynx. As it has both epithelial and mesenchymal components, there are many theories concerning its origin and it can prove a diagnostic challenge. CASE REPORT: A 76 year old male smoker presented with dysphonia. Vocal cord injury was found on examination but no lymphadenopathy or metastases were present. Laryngeal microsurgery was performed with complete excision of the lesion. Histopathology showed it to be a carcinosarcoma which showed intense and diffuse positivity for vimentin and focal positivity for AE1-AE3, CK5 and p63. The patient underwent radiotherapy as complementary treatment. DISCUSSION: Sarcomatoid carcinoma usually presents with obstructive symptoms such as dysphonia. Prognosis depends on the stage and the presence or not of metastases. Both epithelial markers EMA, cytokeratin (AE1-AE3), epithelial membrane antigen, Ki 67 and mesenchymal markers such as vimentin, desmin, S-100 may be positive in these tumours. Recommended treatment for T2-T1 stages is an excisional biopsy which can be followed by adjuvant radiotherapy; radiotherapy alone has also been successful. T3-T4 stages can be treated with local excision, partial laryngectomy or total laryngectomy with subsequent ganglion emptying and concomitant radio and chemotherapy.

Osteosarcoma Arising in Carcinosarcoma De Novo Parotid Gland in a Young Man: An Unusual Case with Review of Literature.

Carcinosarcoma of the parotid gland, a true malignant mixed tumour is extremely rare. It may occur in a pre-existing pleomorphic adenoma or arise de novo. We report a case of carcinosarcoma de novo harbouring an osteosarcomatous element in a 35-year-old man along with review of the reported cases. Excision was done and histopathologic examination confirmed the diagnosis. Long term follow up has been recommended for these tumours owing to their high propensity of recurrence and metastasis. Our case discusses the importance of histopathology and limitation of preoperative imaging in the diagnosis of such an aggressive neoplasm; emphasizing the fact that possibility of carcinosarcoma should be kept in mind while dealing with salivary gland lesions even at a younger age.

A Case Report of Rare Carcinoma Ex Pleomorphic Adenoma of Submandibular Gland and its Detailed Description.

A 65-year-old female patient reported with a chief complaint of swelling in the left lower region of the jaw since two years. On clinical examination, the swelling was present on the mandibular left posterior region and measuring approximately 6.2 cm antero-posteriorly × 6.2 cm mediolaterally × 8.7 cm superioinferiorly. Initially, it was non tender but eventually it became tender. Fine needle aspiration was done to rule out any salivary gland pathology and report obtained was carcinoma ex pleomorphic adenoma. Then, excisional biopsy was taken and tissue sent for histopathology. Histopathological diagnosis was benign adenoma with carcinoma. Later serial sections of tissue were studied and came to the conclusion of carcinoma ex pleomorphic adenoma which was non invasive type and showed bizarre cells with neoplastic changes. Benign part was composed of myxomatous area with partial capsule. Neoplastic cells showed invasion into capsule and few necrotic areas were also present. Overall interpretation was favoured Non invasive carcinoma ex pleomorphic adenoma. So here, we reported a case of Carcinoma ex Pleomorphic Adenoma (CAEXPA) which is a deadly and rare variant of salivary gland malignancy.