Challenging Case of Anaplastic Thyroid Cancer With Unusual Clinical and Histological Features: A Diagnostic Dilemma With Undifferentiated Pleomorphic Sarcoma.

Thyroid cancer is a common malignancy worldwide, and its incidence is increasing rapidly, especially in women. In the majority of cases, it presents solely with a palpable neck swelling. Less commonly, the disease manifests with symptoms of advanced stages, such as superior vena cava (SVC) obstruction and indications of recurrent laryngeal nerve invasion. Anaplastic thyroid cancer is a rare variant of thyroid cancer and is considered to have one of the poorest prognoses, and its diagnosis and treatment are challenging. On the other hand, undifferentiated pleomorphic sarcoma is a differential diagnosis with many clinical and histological similarities, which can only be confirmed through immunohistochemical studies. We herein report a challenging case of a 69-year-old female patient who presented with obstructive symptoms, diagnosed with anaplastic thyroid cancer exhibiting unusual clinical and histological features.

Clinical utility of immunohistochemical subtyping in patients with small cell lung cancer.

OBJECTIVES: Molecular subtyping of small cell lung cancer (SCLC) tumors based on the expression of four transcription factors (ASCL1, NEUROD1, POU2F3, and YAP1) using immunohistochemical (IHC) staining has recently emerged as a proposed approach. This study was aimed to examine this subtyping method in Asian patients with SCLC and investigate its correlation with treatment efficacy. MATERIALS AND METHODS: Seventy-two tumor samples from patients with SCLC, including de novo cases and those transformed from EGFR-mutant tumors, were analyzed. IHC staining was used to measure the expression of the four transcription factors and conventional SCLC markers. Subtypes were defined based on relative expression levels. The treatment response and outcome of patients receiving immune checkpoint inhibitors and chemotherapy were also reviewed. RESULTS: ASCL1 was the most common subtype, observed in 55.2 % of the samples, followed by NEUROD1 (26.9 %) and POU2F3 (9 %). No tumor exhibited predominant YAP1 positivity, while 41.8 % of the samples demonstrated positivity for two subtype markers. Approximately 50 % of the patients experienced a subtype switch after disease progression. Patients with the ASCL1/NEUROD1 (SCLC-A/N) subtype had similar progression-free survival (PFS) compared to non-SCLC-A/N patients after treatment with immune checkpoint inhibitors plus chemotherapy. Transformed SCLC patients had significantly worse PFS than de novo SCLC patients after chemoimmunotherapy. (2.1 vs. 5.4 months, P = 0.023) CONCLUSIONS: This study revealed the challenges associated with using IHC alone for molecular subtyping, highlighting the frequent co-expression of subtypes and temporal changes following treatment. Further research is warranted to explore the prognostic and therapeutic implications of IHC subtyping in patients with SCLC.

Diagnostic value of endoscopic ultrasound-guided tissue acquisition with rapid on-site evaluation performed by endoscopists in immunohistochemistry-required solid pancreatic lesions / 中华胰腺病杂志

Objective:To evaluate the diagnostic value of rapid on-site evaluation (ROSE) performed by endoscopists for solid pancreatic lesions requiring tissue for immunohistochemistry (IHC) staining with different approach of endoscopic ultrasound-guided tissue acquisition (EUS-TA).Methods:After screening 1 573 cases who underwent EUS-TA operation at the Endoscopy Center of Peking Union Medical College Hospital between August 2018 and October 2022, a total of 65 cases of solid pancreatic lesions whose diagnosis rely on IHC staining was collected and summarized with clinical data of each case. Among 65 cases, there were 46 cases of pancreatic neuroendocrine tumors (PNETs), 13 cases of pancreatic solid pseudo-papillary tumors (SPTs), and 6 cases of lymphomas and mesenchymal. Patients were categorized into ROSE group (36 cases) and non-ROSE group (29 cases) according to the presence or absence of endoscopists performed ROSE during EUS-TA operation. They were further divided into subgroups of FNA-ROSE (26 cases), FNB-ROSE (10 cases), FNA-non-ROSE (24 cases) and FNB-non-ROSE (5 cases) according to the type of EUS-TA. Diagnostic accuracy and IHC success rate were compared between different groups and subgroups. Binomial logistic multifactorial regression analysis was used to evaluate the influence of ROSE and EUS-TA type on diagnostic accuracy and IHC success rate.Results:There were no statistically significant differences between ROSE group and non-ROSE group in terms of age, gender, bilirubin level, CA19-9 level, lesion site, lesion size, composition ratio of diagnosis, and surgical rate. The differences in mean size of lesions, needle gauge, location of puncturation, and number of needle pass between subgroups were not statistically significant. The diagnostic accuracy was 88.9% in ROSE group and 79.3% in non-ROSE group, and the difference between the two groups was statistically significant ( P=0.023). The diagnostic accuracy of FNA-ROSE group was higher than that of FNA-non-ROSE group (88.5% vs 75.0%), but the difference was not statistically significant ( P>0.100). The differences in diagnostic accuracy and success rate of IHC between FNB-ROSE group and FNB-non-ROSE group were not statistically significant. Binomial logistic multifactorial regression analysis did not reveal any independent influences on diagnostic accuracy. Conclusions:ROSE performed by endoscopists improved diagnostic accuracy of EUS-TA in solid pancreatic lesions requiring IHC staining, and therefore is potentially valuable for improving the diagnostic efficiency of EUS-TA for such diseases.

Sarcomatoid Intrahepatic Cholangiocarcinoma: A Rare and Aggressive Primary Liver Cancer.

Sarcomatoid intrahepatic cholangiocarcinoma (S-iCCA) is a rare variant of primary liver cancer with a poor prognosis due to local aggressive expansion and frequent metastases. The pathogenesis remains unclear, but theories suggest epithelial-mesenchymal transition, biphasic differentiation of pluripotent stem cells, or sarcomatoid re-differentiation of immature multipotent carcinoma cells. Chronic hepatitis B and C, cirrhosis, and age above 40 are plausible contributors. Diagnosis of S-iCCA requires immunohistochemical evidence of both mesenchymal and epithelial molecular expression. Early detection and total resection are the current mainstay approach. We report a case of metastatic S-iCCA in a 53-year-old male with alcohol use disorder who underwent en bloc right hepatic lobectomy, right adrenalectomy, and cholecystectomy.

Loss of Human Epidermal Receptor 2 Expression in Formalin-Fixed Paraffin-Embedded Breast Cancer Samples and the Rescuing Effect of Enhanced Antigen Retrieval and Signal Amplification.

As an important therapeutic target in breast cancer, HER2 expression assessed by immunohistochemistry plays a critical role in breast cancer treatment. Recent advances in HER2 antibody-drug conjugate therapy have enabled patients with HER2-low expression breast cancer to benefit from the drugs. However, it is not known whether the HER2-low expression in breast cancer FFPE blocks would be lost as storage time increased. In this study, we aimed to assess the loss of HER2 antigenicity in stored FFPE blocks of breast cancer and the rescue effect of modifying the protocol of antigen staining. We selected archived HER2-low breast cancer FFPE blocks with stored time ranging from 1 year to over 15 years and re-detected the expression of HER2. Our study showed that HER2 antigenicity loss increased with storage time and could cause false negativity in HER2-low detection. Moreover, we showed that by either increasing the antigen retrieval time or applying the tyramide signal amplification (TSA) kit, the HER2 signal can be rescued and detected in about half of the cases with HER2-low loss without causing false positivity.

Pericardial Epithelioid Inflammatory Myofibroblastic Sarcoma: An Atypical Presentation.

Sarcomas are a diverse group of cancers of mesenchymal origin. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an uncommon and hardly reported neoplasm that is a malignant variant of the typically benign inflammatory myofibroblastic tumor (IMS). We discuss an exceedingly rare case of a 53-year-old patient with primary EIMS of the pericardium who presented in impending hemodynamic collapse. A transthoracic echocardiogram revealed a large circumferential pericardial effusion with tamponade physiology and an echogenic intrapericardial mass compressing the right ventricle to near obliteration. She underwent emergent sternotomy with resection and one cycle of chemotherapy with liposomal doxorubicin before having recurrent metastatic pericardial and pleural effusions, ultimately leading to her unfortunate passing.

A Collision Tumor in the Breast Consisting of Invasive Ductal Carcinoma and Malignant Melanoma.

Collision tumors are rare neoplasms that consist of at least two different cell lineages at the same site. Given the many possible combinations that can occur, collision tumors, while rare, have been reported in multiple locations such as the stomach, bladder, and thyroid. Collision tumors are rarely found in breast tissue, with only a few cases reported in the literature. We herein report a unique case of a 79-year-old woman with a history of melanoma who presented with a left breast mass that was subsequently found to have invasive ductal carcinoma (IDC) and metastatic melanoma in the breast tissue. This is one of the first reported combinations of these two malignancies.

Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer.

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.

Detection of early myocardial cell death in owl monkeys (Aotus nancymai) using complement component C9 immunohistochemistry in formalin-fixed paraffin-embedded heart tissues: A retrospective study.

BACKGROUND: Owl monkeys are commonly used in biomedical research which is affected by the high incidence of cardiomyopathy in this species. Occasionally, owl monkeys with no clinical signs of heart disease are found dead and at necropsy show no, or very mild, cardiomyopathy. A possible explanation for sudden death is acute myocardial infarction; however, early myocardial changes may be difficult to assess by conventional stains and light microscopy. METHODS: Complement component C9 immunohistochemistry was performed in paraffin-embedded heart tissue samples from owl monkeys who died suddenly, or were euthanized due to sickness, to determine whether these animals suffered from acute myocardial infarcts. RESULTS AND CONCLUSION: C9 deposits were found in the myocardium of 19 out of 20 (95%) animals. The findings in this study suggest owl monkeys suffer from acute myocardial infarcts, and complement component C9 immunohistochemistry may be a useful diagnostic tool.

Prognostic Factor Utility of BAP1 Immunohistochemistry in Uveal Melanoma: A Single Center Study in Spain.

Even today, the mortality rate for uveal melanoma (UM) remains very high. In our research, we sought to determine which pathological and clinical features were correlated with the prognosis of UM. BAP1 (BRCA1-Associated Protein 1) gene mutation has been analyzed as one of the strongest predictors for metastasis in UM. The BAP1 gene codifies the BAP1 protein which has a tumor suppressor function. The presence of this protein can be determined by BAP1 immunohistochemical staining. Eighty-four uveal melanoma patients and forty enucleated eyeballs were examined. Metastasis was present in 24 patients. Nuclear BAP1 staining was low in 23 patients. The presence of a higher large basal diameter tumor (p < 0.001), tumor infiltrating lymphocytes (p = 0.020), and a lack of nuclear BAP1 immunostaining (p = 0.001) ocurred significantly more often in the metastatic group. Metastasis-free survival was lower in patients with low nuclear BAP1 staining (p = 0.003). In conclusion, to the best of our knowledge, this is the first time that BAP1 staining has been studied in uveal melanoma in a Spanish community. We believe that this technique should become routine in the pathological examination of uveal melanoma in order to allow adequate classification of patients and to establish an individual follow-up plan.

Exploring the Rare Etiology of Severe Anemia in an Immunocompromised Patient.

Pure red cell aplasia (PRCA) is a rare cause of profound anemia, marked by very low reticulocyte count and near to complete absence of erythroid precursor cells in the bone marrow. PRCA can be congenital such as in the case of children with Diamond- Blackfan anemia or acquired, which is often triggered by exposure to certain viruses or drugs. Management depends on the underlying etiology of PRCA. Here, we present the case of a young male with underlying acquired immunodeficiency syndrome, who presented with a hemoglobin of 2.6 g/dL, initially thought to be secondary to gastrointestinal blood loss, but was later discovered to have parvovirus-induced PRCA.

Increased carbohydrate antigen 19-9 expression in a thymic neuroendocrine tumor.

Here, we report a case of carbohydrate antigen (CA) 19-9-producing mediastinal neuroendocrine tumor (NET) (atypical carcinoid). A 54-year-old woman with no specific relevant medical history was referred to our hospital because of increased CA19-9 (95.3 U/ml) detected on health screening. Chest computed tomography (CT) revealed an anterior mediastinal mass without localized lymphadenopathy. Thoracic surgery was performed and the histopathological diagnosis was thymic CA19-9-positive NET. The patient developed mediastinal lymph node metastasis at 1 year (CA19-9: 413 U/ml) and multiple bone metastases 4 years (CA19-9: 2303 U/ml) after surgery. Increased CA19-9 levels paralleled the clinical courses of relapse. To our knowledge, this is the first report of CA19-9-producing thymic NET.

MiT family translocation renal cell carcinoma in an elderly male.

Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulate differentiation in melanocytes and osteoclasts. Renal cell carcinomas (RCCs) associated with Xp11 translocations have gene fusions involving TFE3, which has multiple gene partners; RCCs with t(6:11) translocations have MALAT1-TFEB gene fusions. These tumors are histologically diverse, often have papillary, alveolar, and nested growth pattern with clear and eosinophilic cells and psammoma bodies and are seen commonly in children and young adults, accounting to 40% of pediatric RCCs and 1.6%-4% of adult RCCs. The mean and median patient age is 31 years. Thus, distinguishing t-RCC from its morphologic, immunophenotypic, and molecular mimics has important clinical implications. Directed ancillary testing is an essential aspect to t-RCC cases and may include a panel of immunohistochemical stains, such as PAX8, pancytokeratins, AMACR, CD10, and TFE-3. We, hereby report a case of TFE3 positiveXp11 translocation renal cell carcinoma in a 52-year-old male which is unusual.

Clinicopathological correlation and post-resection outcomes of hepatic angiomyolipoma.

BACKGROUNDS/AIMS: Angiomyolipoma is a rare neoplasm of mesenchymal origin derived from perivascular epithelioid cells. Due to rarity, hepatic angiomyolipoma (HAML) has been often misdiagnosed as hepatocellular carcinoma (HCC) or other hypervascular liver tumors based on imaging studies. This study investigated the clinicopathological correlation and post-resection outcomes of HAML. METHODS: This retrospective observational study included 40 patients who underwent hepatic resection (HR) for HAML between 2008 and 2018. RESULTS: Mean age of the patients was 42.6±11.4 years and there were 30 (75.0%) females. Hepatitis B and C virus infection was present in 8 patients (20.0%) and 1 patient (2.5%), respectively. Preoperative diagnoses on imaging studies were HCC in 23 (57.5%) patients, HAML in 14 (35.0%) patients, focal nodular hyperplasia in 2 (5.0%) patients, and hepatic adenoma in 1 (2.5%) patient. Percutaneous liver biopsy was performed in 10 (25.0%) patients and HAML was diagnosed in all patients. Only 3 patients (7.5%) showed a slight elevation in the level of liver tumor markers. Major HR was performed in 10 (25.0%). Laparoscopic HR was performed in 9 (22.5%). The mean tumor size was 4.8±3.9 cm and single tumor was present in 38 (95.0%) patients. Currently, all the patients are alive without tumor recurrence during the follow-up observation period of 75.7±37.3 months. CONCLUSIONS: HAML is a rare form of primary liver tumor and is often misdiagnosed as HCC or other hypervascular tumors. Although HAML is benign in nature, it has malignant potential, thus resection is indicated if the tumor grows or malignancy cannot be excluded.

Prognosis of hepatic epithelioid hemangioendothelioma after living donor liver transplantation.

Background: Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. Due to its rarity and protean behavior, the optimal treatment of hepatic EHE has not yet been standardized. This single-center study describes outcomes in patients with hepatic EHE who underwent living donor liver transplantation (LDLT). Methods: The medical records of patients who underwent LDLT for hepatic EHE from 2007 to 2016 were reviewed. Results: During 10-year period, four patients, one man and three women, of mean age 41.3±11.1 years, underwent LDLT for hepatic EHE. Based on imaging modalities, these patients were preoperatively diagnosed with EHE or hepatocellular carcinoma, with percutaneous liver biopsy confirming that all four had hepatic EHE. The tumors were multiple and scattered over entire liver, precluding liver resection. Blood tumor markers were not elevated, except that CA19-9 and des-γ-carboxy prothrombin was slightly elevated in one patient. Mean model for end-stage liver disease score was 10.8±5.7. All patients underwent LDLT using modified right liver grafts, with graft-recipient weight ratio of 1.11±0.19, and all recovered uneventfully after LDLT. One patient died due to tumor recurrence at 9 months, whereas the other three have done well without tumor recurrence, resulting in 5-year disease-free and overall patient survival rates of 75% each. The patient with tumor recurrence was classified as a high-risk patient based on the original and modified hepatic EHE-LT scoring systems. Conclusions: LDLT can be an effective treatment for patients with unresectable hepatic EHEs that are confined within the liver and absence of macrovascular invasion and lymph node metastasis.

Distinct Histopathology Characteristics in Empty Nose Syndrome.

OBJECTIVES/HYPOTHESIS: Empty nose syndrome (ENS) is a controversial disorder and the change of histopathology has never been discussed. This study aimed to conduct a structured histological review to improve the diagnosis and understanding of ENS. Further immunohistochemical staining of transient receptor potential channel melastatin 8 (TRPM8) was performed. STUDY DESIGN: A prospective case-control study in a tertiary medical center. METHODS: Consecutive patients with ENS who were diagnosed and received surgical intervention after failure of conservative management were included. Patients with benign pituitary gland tumor receiving transsphenoidal excision were enrolled as control group. Biopsy of inferior turbinate was obtained during surgery for histological review and immunohistochemical staining. RESULTS: Seventeen patients with ENS and six patients as a control group were established for structured histological review. Patients with ENS presented significantly more squamous metaplasia, a higher rate of submucosal fibrosis, and a lower submucosal gland number grading. Additionally, a unique histological change called goblet cell metaplasia was found in the ENS group. The respiratory epitheliums of ENS were mostly intact with preservation of ciliated cells and goblet cells. The ENS group had a significantly lower expression level of TRPM8. CONCLUSIONS: The nasal mucosa of ENS experienced some airway remodeling and thermoreceptors downregulation, which contribute to clinical symptoms. The distinct histology of ENS included preserved respiratory epithelium and goblet cell metaplasia, accompanying with characteristics similar to atrophic rhinitis. Biopsy of the inferior turbinate may help diagnose ENS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E14-E18, 2021.

Overlapping tumor-specific expression of p53, p16INK4a, and sirtuin 1 in Bowen's disease: A case report.

Understanding the impact of inactivating mutations in SIRT1 on the p53 and p16 tumor suppressor genes may yield new insight into the oncogenic mechanisms underlying Bowen's disease.

NKX3.1 Identifies Prostatic Origin of Dural Metastasis in the Setting of Negative Prostate-Specific Antigen Stain.

No clear guidelines exist for the appropriate diagnostic workup of an intracranial mass suspected to be a metastasis from unknown primary origin. Dural metastasis from prostatic origin is very rare. Patients with a known history of metastatic prostate cancer who present with a newly discovered lesion on brain imaging require neurosurgical biopsy to confirm diagnosis prior to initiating treatment. Intracranial metastasis from prostate cancer is rare, and dural metastasis is rarer than intraparenchymal metastasis. Current consensus guidelines support immunohistochemical staining with classic markers such as prostate-specific antigen (PSA) to identify prostatic origin. However, PSA detection of prostate metastases declines with higher Gleason scores and in patients undergoing androgen deprivation therapy. NKX3.1 is another stain that is highly sensitive and specific for prostate. Our patient was a 54-year-old man with a history of metastatic prostate cancer who presented with new-onset seizures. Brain imaging revealed a dural-based lesion with surrounding vasogenic edema and midline shift. The patient underwent resection of the lesion, which was stained with multiple cancer markers. Prostate-specific antigen was negative, but NKX3.1 was positive indicating a prostatic origin for the mass. He underwent a craniectomy to remove the lesion and was given steroids. However, he succumbed to his illness several months later. Here, we document the first report to our knowledge of a patient with prostate metastasis to the dura that is PSA negative, but NKX3.1 positive.

Caspase-3, p53 and Bcl-2 expression in basal cell carcinoma of the eyelid.

INTRODUCTION: Eyelid tumours mostly originated from skin and its appendeges. External carcinogens like UV radiation causes cell damages in the eyelid skin and contributes to carcinogenesis. Apoptosis is a very important mechanism to prevent these damage and probable neoplatic change. AIM: To compare caspase-3, p53 and Bcl-2 levels between patients with basal cell carcinoma (BCC) of the eyelid and healthy individuals. MATERIAL AND METHODS: Pathology archives from October 2012 to April 2015 were scanned for BCC biopsies of the eyelid and tissue removed during blepharoplasty and entropion procedures. A total of 36 specimens were found. The specimens were divided into two groups: BCC group and controls (consisting of eyelid tissue removed during routine blepharoplasty). The pathology specimens were then stained using p53, Bcl-2 and caspase-3 stains and the intensity of staining was graded on a 0-3 scale. RESULTS: Samples from a total of 36 patients were included in the study. Eighteen (50.0%) patients were female. There were 13 patients in the BCC group and 23 patients in the control group. The mean age was 66.0 ±10.8 years in the BCC group, and 65.61 ±11.22 years in the control group. The caspase-3 staining was lower in the BCC group than in the control group. No significant differences were found between the BCC group and the control group in terms of p53 levels or Bcl-2 levels (both of them, p = 1.000). CONCLUSIONS: The caspase-3 level was lower in the BCC group. This result suggests that these enzymes can play a significant role in carcinogenesis of eyelid BCC.

Primary Gastrointestinal Stromal Tumor Presenting as an Isolated Lung Mass.

Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal (GI) tumors, representing a small portion of soft tissue tumors of the abdominal cavity. Extraintestinal gastrointestinal stromal tumors (EGISTs) are uncommon forms of GISTs that present outside the GI tract. There have only been a rare number of reported cases of EGIST presenting above the diaphragm. We present the case of a 50-year-old female with shortness of breath, and found to have bilateral pleural effusions and left-sided lung mass. The initial lung mass aspiration was negative for malignancy; yet, pleural fluid was suggestive of malignancy, and repeat biopsy and immunohistochemical stain were diagnostic for GIST. Ultimately, the patient underwent video-assisted thoracoscopic surgery, pleurodesis with doxycycline, and adjuvant therapy with imatinib. This is a report of primary EGIST presenting as an isolated lung lesion with no involvement of the GI tract. In patients with suspected malignancy, it is of paramount importance to obtain a detailed history, including remote signs and symptoms, while performing a thorough work-up. Especially in the lung where initial biopsies can be skewed due to inflammation and atelectasis, repeat biopsies may be necessary to obtain an accurate diagnosis.