High-Grade Malignant Peripheral Nerve Sheath Tumor Arising From Common Peroneal Nerve Neurofibroma.

This article presents a case report of a 45-year-old male with neurofibromatosis type I (NF1) who developed a high-grade malignant peripheral nerve sheath tumor (MPNST) originating from a neurofibroma within the common peroneal nerve over popliteal fossa. MPNSTs are aggressive tumors associated with NF1, causing significant mortality. The patient underwent tumor resection surgery and received postoperative radiation therapy. Follow-up examinations showed no impairment of motor function and no tumor recurrence after regular MRI evaluation for four years. This article explores the challenges of distinguishing benign neurofibromas from malignant MPNST via MRI image and biopsy, and achieving a balance between tumor excision and preserving nerve functionality during surgical treatment. However, caution is warranted due to the risk of recurrence.

Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract.

DEK::AFF2 carcinoma of the sinonasal tract is an emerging entity. The tumor is typically characterized by papillary proliferation of non-keratinizing squamous epithelial cells with monotonous cytologic features, which may mimic other sinonasal tumors. The confirmation of this gene fusion has thus far relied solely on next-generation sequencing, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction (RT-PCR). This current study aimed to validate an immunohistochemical assay for AFF2 C-terminus as an ancillary marker. We first analyzed publicly available RNA sequencing data of sinonasal tumors from the national center for biotechnology information (NCBI) sequence read archive and identified 3 DEK::AFF2 carcinomas out of 28 sinonasal tumors. The gene expression of AFF2 was significantly higher in the fusion-positive cases compared to the wild-type tumors (p < 0.001), while DEK was not. We then optimized an immunohistochemical assay with an anti-AFF2 C-terminus antibody for ancillary diagnosis. Seventeen DEK::AFF2 carcinomas, including 11 cases with predominantly low-grade morphology and one showing glandular differentiation, as well as 78 DEK FISH-negative sinonasal tumors were evaluated by AFF2 immunohistochemistry (IHC). Sixteen of the 17 DEK::AFF2 carcinomas showed nuclear AFF2 expression in ≥30% of tumor cells, including one decalcified case that failed FISH and RT-PCR confirmation. The one case that was negative for AFF2 IHC in the tumor cells also lacked expression in the internal positive control. It was thus considered a failure of the IHC rather than a truly negative case and was excluded from the statistical analysis. All DEK FISH-negative sinonasal tumors were negative for nuclear AFF2 expression. The nuclear expression of AFF2 IHC showed 100% sensitivity and specificity for DEK::AFF2 carcinoma. Accordingly, AFF2 IHC is a highly sensitive and specific ancillary marker that distinguishes DEK-AFF2 carcinoma from the other sinonasal tumors with overlapping morphological features and may be an especially useful alternative for decalcified specimens.

DEK-AFF2 fusion-associated papillary squamous cell carcinoma of the sinonasal tract: clinicopathologic characterization of seven cases with deceptively bland morphology.

A novel DEK-AFF2 fusion has been recently identified in four cases of basaloid to nonkeratinizing squamous cell carcinoma (SCC) in the sinonasal tract and middle ear with high-grade morphology. The exceptional response to immune checkpoint inhibitor in the first reported case highlights the potential clinical importance of identifying tumors with DEK-AFF2 fusions. We herein reported the first series of seven cases of DEK-AFF2 fusion-associated sinonasal SCC with deceptively bland morphology, including four cases of low-grade papillary Schneiderian carcinoma, which is a recently described tumor type with unknown molecular underpinnings. The DEK gene rearrangement was confirmed by DEK break-apart fluorescence in situ hybridization and DEK-AFF2 fusion transcripts were detected by reverse transcription polymerase chain reaction. In contrast to the previously reported DEK-AFF2 fusion-positive high-grade carcinomas, these tumors had a monotonous and bland morphology and were all initially diagnosed as sinonasal papilloma (SP) of various types, with or without dysplasia or carcinoma in situ. The tumor was characterized by mixed exophytic and inverted patterns, broad papillary fronds, acantholytic change, cellular monotony, dense neutrophilic infiltrates, and peripheral palisading. All tumors were diffusely positive for p40 or p63 and negative for NUT and p16. Molecular drivers associated with SP, including EGFR and KRAS mutations and both high and low-risk human papillomavirus infection, were negative in all cases. Although there was no overt stromal invasion or desmoplastic reaction in the initial specimens, these tumors tended to progress locoregionally through a prolonged clinical course and occasionally develop lymph node metastases, high-grade transformation, or extensively local destruction eventually leading to death. These justify more aggressive clinical management. Therefore, we propose the new terminology "DEK-AFF2 fusion-associated papillary SCC of the sinonasal tract" to better describe this clinicopathologically and molecularly distinct entity.

Extensive-Stage Small Cell Carcinoma Transformation From EGFR Del19-Mutant Lung Adenocarcinoma on Gefitinib at the Twelfth-Year Follow-Up Case Report.

INTRODUCTION: The acquired resistance mechanisms in patients with epidermal growth factor receptor (EGFR)-mutant lung cancer, particularly adenocarcinoma (ADC), following treatment with an EGFR tyrosine kinase inhibitor (TKI) have received extensive investigations. The phenotypic transformation to small cell carcinoma (SCCT) has been estimated to occur in approximately 3 to 10% of patients treated with an EGFR-TKI. The prognosis after SCCT is extremely poor. CASE STUDY: We report about SCCT that occurred 45 months after the initial diagnosis of ADC in an East Asian never-smoker woman with advanced-stage EGFR Del-19-mutant lung ADC treated with combined chemoradiotherapy before the era of insurance coverage for EGFR-TKIs in this country and subsequently gefitinib; deletion at codon 746-750 in exon 19 of the EGFR gene was ascertained in the original formalin-fixed paraffin-embedded lung biopsy tissue. Spinal cord compression at thoracic-12 level from SCCT was successfully relieved with neurosurgical treatment, chemotherapy with etoposide and cisplatin, and radiotherapy, while gefitinib treatment was maintained. Eleven months later, SCCT relapsed in the lung parenchyma, which was resected and was found to be sensitive to second-line weekly topotecan. Prophylactic cranial irradiation was subsequently administered. SCCT was confirmed by MALDI-TOF MS analysis of formalin-fixed paraffin-embedded tissues demonstrating the same exon 19 deletion. At the 12th-year follow-up, the patient remains relapse free with very good performance status. The novelty of this case is the successful interdisciplinary team effort to correct the spinal cord compression by maintaining the patient in an ambulatory state, non-stop use of gefitinib justified by the presence of activating EGFR mutation in SCCT tumor cells, and aggressive dose-intensive chemotherapy and radiotherapy for the SCCT that leads to an unprecedented prolonged remission and survival. This case also supports the observation that SCCT is chemotherapy sensitive, and thus, re-biopsy or complete tumor excision is recommended to understand the mutation profiles of the current tumor. Aggressive prudent administration of systemic chemotherapy obtaining optimal dose intensity leads to the successful management of the patient.

A dedifferentiated solitary fibrous tumor of the parotid gland: a case report with Cytopathologic findings and review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT) is a ubiquitous mesenchymal neoplasm but it rarely occurs in the parotid gland. The histological features are variable, with the majority having spindle cell morphology and non-specific branching (staghorn) ecstatic vascular pattern. SFT ranges from benign to overtly malignant. Dedifferentiation within SFTs represents an abrupt transition from a well-differentiated component to a high-grade area, the latter most often including poorly differentiated epithelioid/round cell or high-grade spindle cell morphology. To the best of our knowledge, dedifferentiated SFT in the parotid gland has not been previously reported. CASE PRESENTATION: A 33-year-old woman presented with a soft tissue tumor in the right parotid gland that had been present for 6 months. Fine needle aspiration (FNA) cytology indicated epithelioid morphology in the dedifferentiated component of the tumor, along with metachromatic myxoid matrix. The tumor was initially interpreted as a salivary gland neoplasm of uncertain malignant potential (SUMP).Right partial parotidectomy was performed, and microscopic examination of the resected specimen revealed a malignant spindle cell tumor with a central epithelioid/anaplastic component. The tumor cells were diffusely positive for CD34, STAT-6 and FLI-1, and negative for pan-cytokeratin, CAM5.2, p63, S100 protein, CD31, SMA, and calponin.ERG and Ki67 immunostaining showed an accentuated nuclear staining pattern in the central dedifferentiated area. There was no overexpression of p53 or p16. The patient is currently undergoing regular follow-up and is 11 months postresection with no evidence of recurrence or distant metastasis. CONCLUSIONS: Unlike the typical spindle cell morphology of conventional SFTs, malignant SFTs can show areas of dedifferentiation mimicking an epithelial neoplasm. FNA of dedifferentiated SFTs of the parotid gland may show, a combination of atypical epithelioid cells and metachromatic myxoid/collagenous matrix, which is a less emphasized cytological feature of SFT and may lead to misdiagnosis as a more common parotid gland epithelial neoplasm.

Primary Vaginal Melanoma With Rhabdoid Features: A Case Report and Literature Review.

Primary vaginal melanoma is a rare mucosal neoplasm, which is more aggressive than cutaneous melanoma. Information regarding its morphologic patterns is limited. In particular, the rhabdoid phenotype, mostly observed in metastatic or recurrent cutaneous melanomas, has yet to be reported at this anatomic location. Hence, a potential diagnostic difficulty may arise because of the inability to recognize this unusual histologic variant and its immunohistochemical aberrance. In this report, we describe the case of a primary vaginal melanoma in a 62-year-old woman, who exhibited both rhabdoid and small blue round cell morphologies, absence of S100 protein, and aberrant expression of desmin, CD56, and FLI-1. This report can facilitate the task of expanding the morphologic spectrum of vaginal melanoma, and prevent misdiagnosis and inadequate medical treatment.

The Risks for Ovarian, Endometrial, Breast, Colorectal, and Other Cancers in Women With Newly Diagnosed Endometriosis or Adenomyosis: A Population-Based Study.

OBJECTIVE: Recent studies report a link between endometriosis and ovarian cancer (OC). Using a population-based cohort study to confirm the association between endometriosis and cancer is desirable. We thus examined the magnitude of the risks of OC, endometrial cancer (EC), breast cancer, colorectal cancer (CRC), and other cancers in women with newly diagnosed endometriosis or adenomyosis (internal endometriosis). METHODS/MATERIALS: Women older than 20 years with claims data between 2003 and 2005 were identified from the Longitudinal Health Insurance Dataset containing 1 million individuals randomly sampled from the National Health Insurance Research Database. Those with preexisting malignancies, hysterectomy, or oophorectomy were excluded. The endometriosis cohort (n = 2266, including 768 cases of pure adenomyosis) and comparison cohort (n = 9064), formed by 1:4 matching, were followed up until incidence cancer, dropout, or December 31, 2008. Outcome measures included cancer incidence and adjusted hazard ratio by Cox model adjusted for age group, comorbidities, and endometriosis medication use. RESULTS: With 9842 person-years of follow-up in endometriosis cohort and 36,274 person-years of follow-up in comparison cohort, there were increased risks of all cancers (adjusted hazard ratio, 1.8; 95% confidence interval, 1.4-2.4), OC (4.56, 1.72-12.11), and EC (4.05, 1.20-13.66). The ovarian endometriosis group was associated with increased risk of subsequent OC (4.37, 1.07-17.83). The adenomyosis group was strongly associated with both OC (5.50, 1.95-15.50) and EC (5.13, 1.36-19.40). Increased risk of subsequent CRC was observed in women with adenomyosis with coexistent endometriosis at other sites (13.04, 2.21-77.04). However, no statistically significant increased risk of breast or other cancers was observed. CONCLUSIONS: Having limitations such as lacking of parity information which may affect the magnitude of risk estimates, this study demonstrates that ovarian endometriosis has a 4-fold increased risk of OC. Adenomyosis may associate with a 4- to 5-fold increased risk of OC and EC, and unexpectedly, a 13-fold increased risk of CRC.

Reappraisal of the etiology of extracorpuscular non-autoimmune acquired hemolytic anemia in 2657 hospitalized patients with non-neoplastic disease.

INTRODUCTION: Unlike autoimmune hemolytic anemia (AIHA), literature on the etiological study of non-autoimmune hemolytic anemia (non-AIHA) is scarce. The incidence and prevalence of non-AIHA in different geographic regions are largely unknown perhaps owing to the lack of perspective investigation and different profiles of etiologies from different geographic regions. We aimed to examine the real-world etiology or mechanisms of the non-hereditary non-AIHA from a nationwide population-based administrative claim database in Taiwan. PATIENTS AND METHODS: The National Health Insurance Research Database of Taiwan was adopted for this research. The studied population was total inpatient claim records including both pediatric and adult patients, contributed by a population of 23 million insured individuals in Taiwan. From 2002 to 2008, we retrieved 3,903 patients having no pre-existing malignancy discharged after inpatient management for acquired hemolytic anemia, which was defined as coding in discharge diagnoses containing ICD-9-CM code 283. By contrast, ICD-9-CM code 282 and all of the sub-codes are for hereditary hemolytic anemias. RESULTS: AIHA accounted for 32% of the total cases. Among 2,657 patients with non-AIHA, mechanical or microangiopathic mechanism accounted for 19% of cases; hemolytic-uremic syndrome (HUS) 4%, hemoglobinuria because of hemolysis from external causes such as paroxysmal nocturnal hemoglobinuria (PNH) and march hemoglobinuria 7%, and chronic idiopathic hemolytic anemia or other unspecified non-AIHA 69%. We looked further for specific etiology or mechanism for this group of patients with non-hereditary extrinsic non-AIHA (n = 2,657). The explanatory disease states or conditions were splenomegaly; alcohol use disorder (spur cell hemolysis); heart-valve prosthesis; malignant hypertension; disseminated intravascular coagulation; transfusion reaction; dengue fever-induced hemolytic anemia; direct parasitization; snake, lizard, or spider bite; and Wilson's disease with internal toxin mechanism. All these cases can explain up to 34.6% of all the non-hereditary extrinsic non-AIHA cases. Fragmentation hemolysis (HUS, heart-valve prosthesis, malignant hypertension, and disseminated intravascular coagulation) accounted for 7.4% of non-AIHA hospitalized patients with non-neoplastic disease. CONCLUSIONS: This article is the first one to clearly demonstrate that the non-neoplastic-induced HUS requiring hospitalization cases in Taiwan, which has a population of over 23 million were 110 over a span of seven years, 16 cases per year. Although the etiologies of non-AIHA are well known and described in the literature, this work added the statistical percentages of the various etiologies of non-AIHA in Taiwan.