Uncommon Tumor Research Articles

Urachus carcinoma initially presenting only as a liver metastasis, a diagnostic and therapeutic challenge: First case in literature

Introduction: Urachal carcinomas are uncommon malignant neoplasms comprising only 0.01% of all adult cancers. Most patients were aged from 58 to 64 years at diagnosis with 60 years being the median. It usually metastasizes to the lungs (22%), bones (22%), and liver (16%). Presentation: We report a case of a 71-year-old female patient initially presented with two large liver masses and a small nodule on the anterior side of the bladder. The symptoms were non-specific with abdominal discomfort. The final diagnosis of Urachal Adenocarcinoma was finalized with a biopsy of the bladder mass. The patient initially received six doses of FOLFOX6 without improvement and then Gem-Carbo, showing improvement after six doses. Finally, the patient received two doses of FOLFIRI-B with no response and kept deteriorating and died after 19 months of treatment. Discussion: About 90% of patients are symptomatic and hematuria is the most typical presenting symptom at diagnosis. The low incidence and the histopathologic similarities to adenocarcinoma from various sources pose a difficulty in recognizing the tumor. Our study presents the only case of a urachal carcinoma first manifesting with abdominal mass resulting from liver metastasis with no prior symptoms of urological origins. Also, our study presents the first attempt of using FLOFIRI-B to treat metastatic UraC. Conclusion: This case highlights the necessity for clinicopathological correlation to make the correct diagnosis and the challenges in the treatment which urges the need for further research to identify more effective treatment strategies for this rare cancer.

Correlation of Morphological Appearance of Peritoneal Lesions at Laparotomy and Disease at Pathological Assessment in Patients Undergoing Cytoreductive Surgery for Peritoneal Malignancy: Results of Phase I of the PRECINCT Study in 707 Patients

BackgroundThe PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumors) is a prospective, multicenter, observational study. This report from phase I of PRECINCT outlines variations in recording the surgical peritoneal cancer index (sPCI) at experienced peritoneal malignancy centers and the incidence of pathologically confirmed disease in morphologically different peritoneal lesions (PL).MethodsThe sPCI was recorded in a prespecified format that included the morphological appearance of PL. Six prespecified morphological terms were provided. The surgical and pathological findings were compared.ResultsFrom September 2020 to December 2021, 707 patients were enrolled at 10 centers. The morphological details are routinely recorded at two centers, structure bearing the largest nodule, and exact size of the largest tumor deposit in each region at four centers each. The most common morphological terms used were normal peritoneum in 3091 (45.3%), tumor nodules in 2607 (38.2%) and confluent disease in 786 (11.5%) regions. The incidence of pathologically confirmed disease was significantly higher in ‘tumor nodules’ with a lesion score of 2/3 compared with a lesion score of 1 (63.1% vs. 31.5%; p < 0.001). In patients receiving neoadjuvant chemotherapy, the incidence of pathologically confirmed disease did not differ significantly from those undergoing upfront surgery [751 (47.7%) and 532 (51.4%) respectively; p = 0.069].ConclusionsThe sPCI was recorded with heterogeneity at different centers. The incidence of pathologically confirmed disease was 49.2% in ‘tumor nodules’. Frozen section could be used more liberally for these lesions to aid clinical decisions. A large-scale study involving pictorial depiction of different morphological appearances and correlation with pathological findings is indicated.

Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives.

Gastrointestinal tumors, the second leading cause of human mortality, are characterized by their association with inflammation. Currently, progress in the early diagnosis and effective treatment of gastrointestinal tumors is limited. Recent whole-genome analyses have underscored their profound heterogeneity and extensive genetic and epigenetic reprogramming. Epigenetic reprogramming pertains to dynamic and hereditable alterations in epigenetic patterns, devoid of concurrent modifications in the underlying DNA sequence. Common epigenetic modifications encompass DNA methylation, histone modifications, noncoding RNA, RNA modifications, and chromatin remodeling. These modifications possess the potential to invoke or suppress a multitude of genes associated with cancer, thereby governing the establishment of chromatin configurations characterized by diverse levels of accessibility. This intricate interplay assumes a pivotal and indispensable role in governing the commencement and advancement of gastrointestinal cancer. This article focuses on the impact of epigenetic reprogramming in the initiation and progression of gastric cancer, esophageal cancer, and colorectal cancer, as well as other uncommon gastrointestinal tumors. We elucidate the epigenetic landscape of gastrointestinal tumors, encompassing DNA methylation, histone modifications, chromatin remodeling, and their interrelationships. Besides, this review summarizes the potential diagnostic, therapeutic, and prognostic targets in epigenetic reprogramming, with the aim of assisting clinical treatment strategies.

The Largest Phyllodes Breast Tumor in The World: A Case Report

Phyllodes tumor of the breast is an uncommon fibroepithelial neoplasm constituting 0.3% to 0.5% of female breasttumors. Complete wide local excision is frequently used for treatment and risk reduction in local recurrence. This article aims to report the largest phyllodes breast tumor ever reported worldwide. We report the case of a 24-year-old Thai woman was admitted to our hospital with a massive ulcerofungating right breast mass. Her physical examination revealed a 59 cm diameter mass over her right upper body, in which most parts were infected and ulcerated. A right mastectomy was then performed after the patient had already been treated with intravenous antibiotics for infection control and when her nutrition status had improved. This was followed by Vacuum-Assisted closure of the wound, and split-thickness skin graft, which could be performed after there was a good granulation growth at the wound base. Additionally, after histopathology examination, a 59x53x26 cm malignant Phyllodes tumor with free margins, weighing 14,500 grams, in which there was around 20% tumor necrosis, 12/10 high power fields (HPFs) of Mitosis, and the unaffected nipple was observed. The patient was discharged from the hospital after 45 days, and there was no evidence of local and distant recurrence after a one-year follow-up. Phyllodes tumors are considered unusual fibroepithelial breast tumors that have various biological behaviors, in which surgical resection is a major option for treatment.

Uterine tumors mimicking ovarian sex cord tumors with rhabdoid differentiation: a clinicopathologic study of 4 cases: A case series analysis.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) with rhabdoid features are uncommon mesenchymal neoplasms exhibiting diverse histological patterns, including significant rhabdoid morphology. A thorough comprehension of their clinicopathologic features is crucial for precise diagnosis and effective management. This study presents 4 cases of UTROSCT with rhabdoid features, diagnosed in patients aged 31 to 58. Varied recurrence patterns were observed, including similar recurrent lesions to the primary tumors with subsequent mortality, initial invasion and lymph node metastasis, and presence of only primary tumor. Histopathological examination revealed diverse morphological patterns, prominently featuring rhabdoid differentiation. Immunohistochemical analysis showed expression of hormone receptors, sex cord, smooth muscle, and epithelial markers, notably WT1, CD56, and CD99. Molecular analysis identified ESR1-NCOA2 fusions and ESR1 and NCOA2/3 rearrangements, indicating a potential association between these genetic alterations and extensive rhabdoid differentiation. Various treatments were administered post-recurrence, including chemotherapy and targeted therapies. However, poor clinical outcomes were observed in all cases. Despite aggressive treatments, including chemotherapy and targeted therapies, poor clinical outcomes were observed, highlighting the aggressive nature of UTROSCT with significant rhabdoid differentiation. This case series emphasizes the importance of detailed pathological reporting, comprehensive molecular testing, and thorough tumor staging in UTROSCT cases with rhabdoid features. Enhanced understanding of the clinicopathologic characteristics of UTROSCT with rhabdoid differentiation is crucial for accurate diagnosis, prognostication, and management strategies.

Hippo pathway effectors YAP, TAZ and TEAD are associated with EMT master regulators ZEB, Snail and with aggressive phenotype in phyllodes breast tumors

BackgroundPhyllodes tumors (PTs) of the breast are uncommon fibroepithelial neoplasms that tend to recur locally and may have metastatic potential. Their pathogenesis is poorly understood. Hippo signaling pathway plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. Hippo signaling dysfunction has been implicated in cancer. Recent evidence suggests that there is cross-talk between the Hippo signaling key proteins YAP/TAZ and the epithelial-mesenchymal transition (EMT) master regulators Snail and ZEB. In this study we aimed to investigate the expression of Hippo signaling pathway components and EMT regulators in PTs, in relation to tumor grade. MethodsExpression of Hippo signaling effector proteins YAP, TAZ and their DNA binding partner TEAD was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 86 human phyllodes breast tumors (45 benign, 21 borderline, 20 malignant), in comparison with tumor grade and with the expression of EMT-related transcription factors ZEB and Snail. ResultsNuclear immunopositivity for YAP, TAZ and TEAD was detected in both stromal and epithelial cells in PTs and was significantly higher in high grade tumors. Interestingly, there was a significant correlation between the expression of YAP, TAZ, TEAD and the expression of ZEB and SNAIL. ConclusionsOur results originally implicate Hippo signaling pathway in PTs pathogenesis and suggest that an interaction between Hippo signaling key components and EMT regulators may promote the malignant features of PTs.

Pediatric atypical teratoid/rhabdoid tumor in the cauda equina with rapid tumor progression: illustrative case.

Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon malignant neoplasm and rarely occurs in the spinal space, especially in the cauda equina. Only 8 cases of pediatric AT/RT of the cauda equina have been reported. Therefore, its clinical behavior and optimal treatment remain unclear. The authors describe the case of a 9-year-old boy who presented with progressive back and left leg pain. Initial magnetic resonance imaging showed an intradural extramedullary lesion at the L3-4 level, which progressed rapidly to the L2-5 level within a month. He underwent partial resection of the tumor with an L2-5 laminectomy. The histopathological diagnosis was AT/RT. He received adjuvant chemotherapy and radiotherapy, and his gait disturbance improved postoperatively. At 6 months' follow-up, disease recurrence was not observed. Although extremely rare, AT/RT should be included in the differential diagnosis for prompt therapeutic intervention. Safe resection with minimal functional impairment, followed by postoperative chemoradiation, can lead to tumor control and improve neurological function. https://thejns.org/doi/10.3171/CASE24219.

Interdigitating Dendritic Cell Tumour: A Rare Case Report with Review of Literature

Background and Aims: Interdigitating dendritic cell tumour/sarcoma (IDCS) is an exceedingly uncommon and aggressive tumour with a dismal prognosis. IDCS arises from antigen-presenting cells, which involve nodal and extranodal sites. The aim of the study is to evaluate a case of IDCS and its diagnostic challenges. Methods: A 21-year-old female with no comorbidities, a bone marrow aspirate and biopsy and an excision biopsy of the lymph node shows atypical mononuclear infiltrates that were immunohistochemically positive for S100-diffuse, CD68, LCA and Ki67. Results: Here, we report a single case of IDCS with a tumour arising from the lymph node and bone marrow infiltration. Discussion: IDCS is an aggressive disease with uncertain behaviour; strong suspicion is required to establish a diagnosis.

Descriptive epidemiology of 399 histologically confirmed newly diagnosed meningeal solitary fibrous tumours and haemangiopericytomas in France: 2006-2015.

Meningeal solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) are uncommon tumours that have been merged into a single entity in the last 2021 WHO Classification of Tumors of the Central Nervous System. To describe the epidemiology of SFT/HPC operated in France and, to assess their incidence. We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed SFT/HPC between 2006 and 2015. Our study included 399 SFT/HPC patients, operated in France between 2006 and 2015, in one of the 46 participating neurosurgical centres. The incidence reached 0.062, 95%CI[0.056-0.068] for 100,000 person-years. SFT accounted for 35.8% and, HPC for 64.2%. The ratio of SFT/HPC over meningioma operated during the same period was 0.013. SFT/HPC are about equally distributed in women and men (55.9% vs. 44.1%). For the whole population, mean age at surgery was 53.9 (SD ± 15.8) years. The incidence of SFT/HPC surgery increases with the age and, is maximal for the 50-55years category. Benign SFT/HPC accounted for 65.16%, SFT/HPC of uncertain behaviour for 11.53% and malignant ones for 23.31%. The number of resection progresses as the histopathological behaviour became more aggressive. 6.7% of the patients with a benign SFT/HPC had a second surgery vs.16.6% in case of uncertain behaviour and, 28.4% for malignant SFT/HPC patients. Meningeal SFT and HPC are rare CNS mesenchymal tumours which both share common epidemiological characteristics, asserting their merging under a common entity. SFT/HPC incidence is less that one case for 1 billion per year and, for around 100 meningiomas-like tumours removed, one SFT/HPC may be diagnosed. SFT/HPC are equally distributed in women and men and, are mainly diagnosed around 50-55years. The more aggressive the tumour, the higher the probability of recurrence.

Various Markers of Neuroendocrine Tumor: A Narrative Review.

Neuroendocrine tumors (NETs) are uncommon tumors that develop from specialized endocrine cells. Thyroid medullary carcinoma, phaeochromocytomas, pituitary tumors, carcinoid, and gastroenteropancreatic NET are just a few examples of the diverse group known as NET. In recent times, they have garnered significant interest due to their ease of palliation and ability to reveal the long-term impact of the specific hormone raised. Neuroendocrine indicators, particularly chromogranin A, are very helpful in the diagnostic process. Accurate biomarkers that can be employed for NET diagnosis, prognosis and follow-up, therapy stratification, and treatment response evaluation are greatly needed. Due to the great diversity of neuroendocrine neoplasms, particular biomarkers must be developed in order to diagnose, treat, and identify them. The several NET biomarkers covered in this review will aid in the fight against this uncommon illness.

Malignant Phyllodes Tumour with Heterologous Osteosarcomatous differentiation and Osteoclast-like giant cells: Case Report of an uncommon neoplasm

Background: Phyllodes tumour (PT), an uncommon fibroepithelial neoplasm accounts for less than 1% of all primary tumours of the breast. MPT with osseous differentiation often gets misdiagnosed on imaging as benign giant calcifications resulting in treatment delay. We describe a rare case of MPT with heterologous osteosarcomatous differentiation and osteoclast-like giant cells and review the literature to discuss clinical-radiological findings, differential diagnosis and treatment options. Case Presentation: A 34-year-old female presented with a right breast lump. Mammography showed a high-density irregular mass with amorphous dense calcification, suggesting neoplastic aetiology. Preoperative core needle biopsy raised the possibility of a phyllodes tumour versus giant cell tumour. Wide local excision was performed to confirm the diagnosis which revealed the presence of a biphasic tumour with osteoid-like matrix and numerous osteoclastic giant cells. Immunohistochemistry was used to rule out metaplastic carcinoma or carcinosarcoma. The stromal cells were negative for panCK and P63 and positive for vimentin, CD10 and BCL-2. The osseous component was positive for Osteonectin and SATB2. Thus, a final diagnosis of malignant phyllodes tumour with heterologous osteosarcomatous differentiation and osteoclast-like giant cells was made. Conclusion: MPT with osteosarcomatous differentiation is a rare and challenging entity associated with a poor clinical outcome. Accurate diagnosis requires a multidisciplinary approach involving breast surgeons, pathologists and radiologists with careful histopathological examination. Wide local excision with close surveillance is crucial for timely detection of tumour recurrence and metastasis.

Solid pseudopapillary tumour of the pancreas: an uncommon pancreatic tumour in Sri Lanka

Introduction and objectives: Solid pseudopapillary tumour of the pancreas (PST) is a rare exocrine pancreatic tumour commonly involving the body and the tail of the pancreas. It's seen predominantly in young women. Even patients who present with metastatic disease have good survival after resection. We looked at our experience with this rare tumour.Methods: Prospectively collected proforma-based data were analysed.Results: 14 patients underwent surgery for PST from November 2011 to October 2022. 13 (93%) were females. The median age was 28 years (15-50). Nine (64.3%) patients presented with abdominal pain, and 3(21.4%) had an abdominal mass at presentation. Only 2(14.3%) patients were incidentally detected. The median tumour diameter was 7.2cm (2-18).7(50%) had involvement of the pancreatic body, 6(43%) had involvement of the head of the pancreas, and one had involvement of both the head and the body of the pancreas. Only one patient (7.14%) had liver metastasis at presentation. Distal pancreatectomy was performed in 6(43%), Whipple’s pancreaticoduodenectomy in 6(43%), enucleation in 1(7.14%) and total pancreatectomy in 1(7.14%). In addition, liver metastasectomy was done in 1(7.14%) patient. There were no major complications. None received adjuvant treatment. At a median follow-up of 22 months, there were no recurrences.Conclusions: PST in our cohort were in young females who had excellent survival after surgical resection. Involvement of the head of the pancreas was common compared to the predominantly distal disease in the available literature.

Intramuscular lipomas posing diagnostic and pre-operative counselling challenges in a low-resource setting: A case series

IntroductionIntramuscular lipomas (IMLs) are uncommon primary adipose tissue tumours deep within the muscle. A high likelihood of misdiagnosing them as other benign and malignant masses necessitates imaging studies to confirm the diagnosis and plan treatment. Ultrasonography is useful but CT and MRI provide a more accurate diagnosis. While diagnostic tests are suitable, they may not always be accessible or affordable in low-resource settings. We present three cases of IMLs that emphasise the difficulties posed by limited resources and the significance of a comprehensive medical history and physical examination in low-resource settings. Presentation of casesThe patients included a 57-year-old male with a distal right thigh mass, a 65-year-old female with a proximal right thigh mass, and a 60-year-old female with a mass at the left scapular area. The three patients underwent surgical excision and had an uneventful postoperative course, with no reported recurrence during their ongoing follow-up. DiscussionThe management of IMLs is not complicated if the requisite resources are available. Conversely, in low-resource settings with limited diagnostic facilities and human expertise, management may take a challenging path. Patient 1, despite undergoing diagnostic tests confirming IML, initially declined treatment due to challenges with pre-operative counselling. Patients 2 and 3 lacked health insurance and could not afford diagnostic imaging tests. ConclusionHealthcare professionals in low-resource settings should familiarise themselves with the clinical characteristics and pathology of IMLs to minimise misdiagnosis and ensure appropriate counselling is provided to patients. IMLs are slow-growing mostly asymptomatic benign swelling. On physical examination, they are usually non-tender, soft, masses, not fixed to the bed or overlying tissue. The overlying skin is normal and lymphadenopathy is absent.

Unusual neuroendocrine tumor in unusual site: a case report and review of literature

Paragangliomas (PGL) are uncommon tumors that develop in the extra-adrenal chromaffin cells of the autonomic nervous system. They are usually found in the retroperitoneum along the abdominal para-aortic region. PGL arising near the pancreas are extremely rare. These tumors can be difficult to diagnose as they can resemble more common pancreatic tumors, making it challenging for clinicians, radiologists, and pathologists alike. In this report, we describe a case of PGL that originated in the pancreaticoduodenal groove, which was initially diagnosed as a neuroendocrine tumor arising from the second part of the duodenum. The patient underwent pancreas-preserving surgery to remove the tumour.

Comparative Analysis of Supratentorial Intraventricular Tumors in Adults and Pediatrics in a Developing Country: Clinicopathological Features, Surgical Management, and Outcomes.

Supratentorial intraventricular tumors, encompassing lateral and third ventricular tumors, are uncommon intracranial neoplasms, typically slow-growing and benign, manifesting symptoms only upon reaching a substantial size. This study aims to identify optimal surgical approaches, assess the prevalence and characteristics of these tumors, and evaluate postoperative outcomes among pediatric and adult age groups. A retrospective comparative study at a tertiary care hospital from January 2014 to June 2020 included 165 patients (68 pediatrics, 97 adults) meeting inclusion criteria for intraventricular tumor management. Data covered demographic factors, clinical history, neurological assessments, neuroimaging, surgical approaches, histopathological diagnoses, immunohistochemical features, adjuvant therapies, follow-up status, postoperative complications, and morbidity/mortality. Ventricular tumor incidence showed male preponderance in both adults (M:F = 1.2:1) and pediatrics (M:F = 3:1). Lateral ventricles were the most common location. Pediatric cases exhibited more frequent calcifications on computed tomography scans (35.6% vs. 29.5%). Grade II and III tumors were more prevalent in adults within the lateral ventricle (27.1 and 1.9%) compared with pediatrics (6.5 and 8.4%). The third ventricle predominantly featured benign lesions, with pediatric patients experiencing significantly longer hospital stays (16.12 ± 21.94 days vs. 9.58 ± 6.21 days) (p = 0.006). Adults and pediatric patients showed a significant difference in high-grade lateral ventricle tumors (p-value = 0.002*). Supratentorial ventricular tumors are relatively more prevalent in children than adults, presenting challenges due to size and bleeding risks. Surgical resection is the primary treatment, with a focus on the optimal approach for gross total excision to reduce recurrence risk.

Demographic and clinical data of patients with spinal epidural angiolipomas

Spinal epidural angiolipomas are rare, benign, mesenchymal tumors. It remains unclear whether spinal epidural angiolipomas are genuinely rare or merely underreported. Herein, we assessed the demographic and clinical characteristics of patients with spinal epidural angiolipoma. We collected data from patients with spinal epidural angiolipoma from three sources. First, we retrospectively analyzed data from patients diagnosed with spinal epidural angiolipoma in our hospital between January 1, 2014, and December 31, 2023. Second, we performed a literature review of studies retrieved from PubMed. Third, we retrieved detailed data of patients with spinal angiolipoma from the Surveillance, Epidemiology, and End Results (SEER) database. We conducted a descriptive analysis to investigate the demographic and clinical characteristics of patients with spinal epidural angiolipoma. At our institution, three patients were diagnosed with spinal epidural angiolipoma. Additionally, we identified 116 patients from the literature review and 15 patients from the SEER database. We reviewed the treatment history and imaging features of the three patients from our institution. The descriptive analysis of the data collected from the literature review was consistent with previous reports. For example, 63.0% of lesions were located at the thoracic level. 31.9% of these lesions involved two vertebral bodies, while 75.6% involved 2–4 vertebral bodies. The most common symptoms experienced by patients were back pain, paraparesis, and numbness in the legs. Surgery was the primary treatment option for most patients, and complete tumor resection was achieved in the majority of patients. The male:female ratio was 1:1.4, the median age at diagnosis for the patients from the literature was 49 years old, and the median follow-up was 24 months. Notably, most of the reports came from Asia and there were few reports from Africa. The findings from the SEER database indicated a male:female ratio of 2:1. The peak incidence, which is typically reported in the fifth decade of life, was not observed. We presented three cases of spinal epidural angiolipoma and supplemented our findings with a literature review and population-based analysis according to the SEER database for the United States population. We believe that our research will enhance clinicians’ comprehension of this uncommon tumor.

Uterine Angioleiomyoma: Clinical and Histopathologic Differentiation of an Underrecognized Mimicker of Uterine Leiomyoma.

Angioleiomyoma is an uncommon benign neoplasm of mesenchymal origin that arises from perivascular smooth muscle cells. This soft tissue neoplasm usually occurs in the dermal or subcutaneous tissues of the extremities, head and neck, or trunk with fewer than 40 reported angioleiomyomas arising in the uterine corpus. Herein we report a uterine angioleiomyoma in a 44-year-old G5P4 Hispanic woman with a longstanding history of recurrent abdominal pain, pelvic organ prolapse, abnormal uterine bleeding, anemia, and hypertension. The patient underwent surgical treatment with total laparoscopic hysterectomy with bilateral salpingectomy and a uterosacral ligament suspension. Uterine angioleiomyoma was diagnosed post-operatively based on gross and microscopic features. The location of the uterine angioleiomyoma within the myometrium corresponded with contrast enhancement apparent on preoperative imaging. This and other uterine angioleiomyomas have characteristic imaging, macroscopic, and microscopic features which distinguish it from leiomyoma. Enhancing awareness of this underrecognized entity will facilitate precise diagnosis and thereby enable improved understanding of the clinicopathological characteristics of uterine angioleiomyoma.

Clinicopathologic and molecular study of superficial CD34-positive fibroblastic tumours mimicking atypical fibrous histiocytoma (dermatofibroma).

Superficial CD34-positive fibroblastic tumour (SCD34FT) is an uncommon but distinctive low-grade neoplasm of the skin and subcutis that shows frequent CADM3 expression by immunohistochemistry (IHC). In this study, prompted by an index case resembling 'atypical fibrous histiocytoma (FH)' that was positive for CADM3 IHC, we systematically examined a cohort of tumours previously diagnosed as 'atypical FH' by applying CADM3 and fluorescence in situ hybridization (FISH) for PRDM10 rearrangement, to investigate the overlap between these tumour types. Forty cases of atypical FH were retrieved, including CD34-positive tumours (n = 20) and CD34-negative tumours (n = 20). All tumours were stained for CADM3. All CADM3-positive tumours were evaluated by FISH to assess for PRDM10 rearrangement. Eleven CD34-positive tumours (11/20, 55%) coexpressed CADM3 and were reclassified as SCD34FT. None (0/20) of the CD34-negative atypical FH were CADM3-positive. Reclassified SCD34FT (10/11) arose on the lower extremity, with frequent involvement of the thigh (n = 8). Features suggestive of atypical FH were observed in many reclassified cases including variable cellularity, spindled morphology, infiltrative tumour margins, collagen entrapment, epidermal hyperpigmentation, and acanthosis. Variably prominent multinucleate giant cells, including Touton-like forms, were also present. An informative FISH result was obtained in 10/11 reclassified tumours, with 60% (6/10) demonstrating PRDM10 rearrangement. A significant subset of tumours that histologically resemble atypical FH, and are positive for CD34, coexpress CADM3 and harbour PRDM10 rearrangement, supporting their reclassification as SCD34FT. Awareness of this morphologic overlap and the application of CADM3 IHC can aid the distinction between SCD34FT and atypical FH.

Aggressive Metastatic Insulinoma in a Patient of Diabetes Mellitus with Documentation on Dual-Tracer PET-CT ([68Ga]Ga-DOTATATE and [18F]FDG): Clinical Benefits with Combined Chemo-PRRT Approach

AbstractInsulinoma is a relatively uncommon pancreatic neuroendocrine tumor, with approximately 10% of the cases being malignant. Diabetes mellitus (DM) with concurrent insulinoma is very rare and the diagnosis of such condition is easily missed as it can be misconstrued as improved glycemic control. Therefore, persistent hypoglycemic symptoms even after stopping antidiabetic medications may be considered for insulinoma. Herein, we present a patient with DM and pancreatic insulinoma with extensive hepatic and skeletal metastases on dual-tracer positron emission tomography/computed tomography (PET/CT) ([68Ga]Ga-DOTATATE and [18F]fluorodeoxyglucose). Given the extensive disease, the patient was treated with a combination of peptide receptor radionuclide therapy (PRRT) and chemotherapy (capecitabine and temozolomide). During therapy, patient showed early clinical and imaging response for insulinoma leading to unmasking of poor glycemic control necessitating requirement of insulin administration for DM. The patient did not experience any life-threatening hypoglycemia during the chemo-PRRT treatment and showed an improvement in quality of life. Unfortunately, the disease progressed at the 4th cycle, 10 months after the initiation of PRRT. We conclude that combined chemo-PRRT may be considered an effective treatment option for patients with metastatic insulinoma and DM owing to its favorable imaging response and effective symptom control.

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR’s, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.