Low-grade central osteosarcoma (LGCOS), which arises from the intramedullary cavity of the metaphysis of long bones, occasionally exhibits extraosseous spread. Approximately 10-30% of patients with LGCOS exhibit dedifferentiation, but it is rare to experience a primary tumor with a dedifferentiated component. A 38-year-old female patient presented with right knee pain for two months. Imaging studies revealed a bone mass with extraosseous involvement. Wide resection was performed, and pathologic examination led to the diagnosis of LGCOS with a dedifferentiated extraosseous lesion. A single defect in the bone cortex constituted the boundary between the low- and high-grade components. The extraosseous high-grade component included more tumor cells with p53 overexpression and more murine double minute 2 (MDM2) copies compared with the low-grade component. These genetic mutations and copy number alterations can be associated with malignant transformation of LGCOS.

OBJECTIVE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications.
METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes.
RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group.
CONCLUSIONS: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

The dedifferentiation of the gastrointestinal stromal tumors (GISTs) has been reported in a small number of cases, usually under the pressure of the tyrosine kinase inhibitor (TKI) treatment. Herein, we described a de novo dedifferentiated GIST with the SDH deficiency in a 32-year-old Chinese woman. The tumor was located on the lesser curvature of the gastric antrum, measuring 4.1x9.1 cm2. Microscopically, the tumor was composed of 2 distinct morphological populations, mild epithelioid cells arranged in the multinodular growth pattern and hyperchromatic spindle cells arranged in the fascicular or sheet-like architecture. The two zones showed different immunophenotypes. The former proved to be an epithelioid GIST with the positive expression for C-KIT, DOG-1, and CD34, and the latter expressed the CKpan and P53, but negative for the C-KIT, DOG-1, and CD34. However, the SDHB staining was negative in both areas. Genetically, the next-generation sequencing (NGS) analysis showed the SDHC mutation (p.S48*) in both components and the MDM2 amplification was only in the spindle cell area. The lesion was diagnosed as the SDH-deficient GIST with the epithelial cell dedifferentiation. We proposed that the P53 associated gene alteration or other alternative escape mechanisms for the KIT-independent signaling pathways might play a role in the dedifferentiation.

We report the first case of bile duct mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) that had a mucinous carcinoma component. An 88-year-old man with biliary obstruction was diagnosed as having distal bile duct cancer using imaging examinations and endoscopic biopsy. The patient received the best supportive care without surgical resection for 13 months until death. An autopsy revealed a bulky mass involving the distal bile duct and multiple metastases in intra-abdominal lymph nodes, the liver, and the lungs. The primary cancer was microscopically diagnosed as a MiNEN, which consisted of mucinous adenocarcinoma and large cell-type neuroendocrine carcinoma (NEC) components. Metastatic lesions in the liver and lungs were composed of only NEC with rich extracellular mucin without adenocarcinoma cells. Using electron microscopy and immunohistochemistry, it was proved that all NEC cells in both primary and metastatic lesions had amphicrine features. On the basis of pathological findings, we thought that the MiNEN was initially derived from a mucinous adenocarcinoma that dedifferentiated to amphicrine NEC cells with mucin production.

Primary breast liposarcoma is an extraordinarily rare breast malignancy. Histological subtypes including dedifferentiated are confirmed after a thorough histopathological and immunohistochemistry analysis. Liposarcoma of the breast can mimic other breast lesions. Long-term follow-up is needed due to the risk of local recurrence and delayed dedifferentiation.

Epithelial myoepithelial carcinoma (EMC) is an uncommon low-to-intermediate grade salivary gland malignancy that accounts for 1% of all tumors arising in salivary glands. About 80% of these tumors affect the parotid gland. These lesions either arise de novo or from existing pleomorphic adenoma (PA). Histologically, these tumors reveal a biphasic cell population with inner ductal epithelial cells and peripheral myoepithelial cells. There are many histologic variants of EMC, but sebaceous, verocay-like differentiation and high-grade transformation is very rarely reported. This article describes a 48-year-old female patient diagnosed with EMC ex PA with unique histologic differentiation.

Malignant melanoma is known to have an altered phenotype and loss of differentiation markers for melanoma due to metastasis. Here, we report a case in which the expression of the immunohistochemical markers for melanoma was changed due to lymph node metastasis of primary cutaneous malignant melanoma. The patient, a male in his 60s, was diagnosed with malignant melanoma after undergoing excision of a skin mass. The additional excision specimen showed a small number of tumor cell clusters infiltrating the dermis. The biopsied lymph node showed completely different histological findings from those of the skin lesion and consisted of spindle-shaped tumor cells. An immunohistochemical study revealed no significant positive reactions in the lymph node tissue indicative of melanoma. The additional genetic study revealed BRAF V600e mutations in both the primary tumor and a lymph node. Together with the histological findings, the diagnosis was of metastasis of dedifferentiated melanoma to a lymph node. In summary, there is a risk of underestimation or misdiagnosis of melanoma as undifferentiated sarcoma or other tumors when melanoma metastasizes to lymph nodes and findings show a dedifferentiated or undifferentiated tumor. Therefore, as in this case, it is necessary to add a genetic study in order to make a comprehensive judgment.

Acinic cell carcinoma (ACC) is a low or intermediate-grade malignant epithelial neoplasm of the salivary glands that generally shows an indolent behavior. Most cases arise in the major salivary glands, especially the parotid gland. ACC is usually known as a low-grade malignant tumor; however, poorly differentiated and high-grade transformed variants have been reported and may tend to be late recurrence and metastasis. Our case was a 49-year-old woman with a history of a right parotid rapidly growing mass lesion, which was cytologically diagnosed as monomorphic adenoma on fine-needle aspiration (FNA). Finally, the diagnosis of ACC with dedifferentiated components was reported, followed by parotidectomy. After 30 sessions of radiotherapy, she presented with hemifacial paresis. An imaging examination of the brain showed intracranial hemorrhage, and she underwent a craniotomy. We performed histopathological and immunohistochemical (IHC) examinations and diagnosed metastatic ACC with dedifferentiated components. Few ACC cases with dedifferentiated components and with aggressive behavior have been reported in the literature , and to the best of our knowledge, this article is the first English report in Iranian population.

Dedifferentiated liposarcoma is a unique subtype of liposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.

Adamantinoma of long bones is a slow-growing, low-grade primary malignant bone tumor. It is a rare entity and accounts for less than 1% of all primary bone tumors, and in most cases, it occurs in the mid-axis of the tibia of adolescents and young adults. In this report, we describe the case of a 53-year-old woman with a diagnosis of adamantinoma of the left tibia who was initially treated surgically in 2004. Two years later, she presented with local relapse, for which she underwent new surgical management. The patient was referred to our practice 16 years after the initial diagnosis, and she presented with recurrence characterized by ipsilateral inguinal lymph node metastasis. The histological findings and immunohistochemistry were compatible with metastatic adamantinoma with high-grade differentiation, which ultimately required surgical salvage management.