Rare Subtype Research Articles

Amelanotic Melanoma—Biochemical and Molecular Induction Pathways

Amelanotic melanoma (AM) is a subtype of hypomelanotic or completely amelanotic melanoma. AM is a rare subtype of melanoma that exhibits a higher recurrence rate and aggressiveness as well as worse surveillance than typical melanoma. AM shows a dysregulation of melanin production, cell cycle control, and apoptosis pathways. Knowing these pathways has an application in medicine due to targeted therapies based on the inhibiting elements of the abovementioned pathways. Therefore, we summarized and discussed AM biochemical and molecular induction pathways and personalized medicine approaches, clinical management, and future directions due to the fact that AM is relatively rare. AM is commonly misdiagnosed. Hence, the role of biomarkers is becoming significant. Nonetheless, there is a shortage of biomarkers specific to AM. BRAF, NRAS, and c-KIT genes are the main targets of therapy. However, the role of BRAF and KIT in AM varied among studies. BRAF inhibitors combined with MAK inhibitors demonstrate better results. Immune checkpoint inhibitors targeting CTLA-4 combined with a programmed death receptor 1 (PD-1) show better outcomes than separately. Fecal microbiota transplantation may overcome resistance to immune checkpoint therapy of AM. Immune-modulatory vaccines against indoleamine 2,3-dioxygenase (IDO) and PD ligand (PD-L1) combined with nivolumab may be efficient in melanoma treatment.

PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer.

The heterogeneity of ovarian cancer (OC) has made developing effective treatments difficult. Nowadays, hormone therapy plays a growing role in the treatment of OC; however, hormone modulators have had only limited success so far. To provide a more rigorous foundation for hormonal therapy for different OC subtypes, the current study used a series of bioinformatics approaches to analyse the expression profiles of genes encoding membrane progesterone (PGRMC1, progestins and the adipoQ receptor [PAQR] family), and androgen (zinc transporter member 9 [ZIP9], OXER1) receptors. Our work investigated also their prognostic value in the context of OC. We found differences in expression of ZIP9 and OXER1 between different OC subtypes, as well as between patient tumour and normal tissues. Expression of mRNA encoding PAQR7 and PAQR8 in a panel of OC cell lines was below the qPCR detection limit and was downregulated in tumour tissue samples, whereas high expression of PGRMC1 and PAQR4 mRNA was observed in rare subtypes of OC cell lines. In addition, chemical inhibition of PGRMC1 reduced the viability of rare OCs represented by COV434 cells. In conclusion, PGRMC1 and PAQR4 are promising targets for anticancer therapy, particularly for rare subtypes of OC. These findings may reflect differences in the observed responses of various OC subtypes to hormone therapy.

Comparative analysis of testicular and non-testicular choriocarcinoma: a population-based study

Background: Germ cell tumors (GCTs) are common solid tumors in young men, originating in the testicles or outside the gonads. Choriocarcinoma, a rare and aggressive subtype, primarily affects females but can also occur in males. Treatment options depend on the stage and location of the tumor, with early recognition being crucial for better outcomes. Comparative studies between testicular and non-testicular choriocarcinoma are crucial for understanding distinct features and prognoses. Methods: The study utilized SEER*Stat software to extract data and applied statistical methods such as chi-square analysis and Kaplan-Meier method. Inclusion criteria focused on patients diagnosed with choriocarcinoma between 2000 and 2018, while exclusion criteria eliminated cases without histological confirmation or with other tumors. Results: Among 363 patients, 270 (74.4%) had testicular CC, and 93 (25.6%) had non-testicular CC. Notably, testicular CC was more common in white patients, which could indicate demographic or environmental factors at play. Patients with testicular CC were more likely to undergo surgery, suggesting a significant treatment trend. It’s worth exploring whether patient preferences or observed post-surgery improvements contribute to this pattern. Testicular CC had a higher 5-year OS rate of 54% versus 29%, and a higher 5-year CSS rate of 56.3% versus 31.9%, respectively. Conclusion: This study reveals distinct characteristics and treatment responses in testicular and non-testicular choriocarcinoma, emphasizing the need for personalized management based on subtype. Our findings highlight racial disparities in incidence and the efficacy of surgical intervention for both types, while chemotherapy benefits extragonadal cases and radiotherapy’s role requires further evaluation.

The diagnostic challenge of differentiating Tumefactive Multiple Sclerosis (TMS) from other brain lesions: a case report and literature review on a rare subtype of MS

Introduction and Importance: This case report is a clinical diagnosis walk through of a rare subtype of Multiple sclerosis (MS). It gives an overview of how Tumefactive multiple sclerosis (TMS) is systematically narrowed down as the definitive diagnosis. Case Presentation: Our 29 year old male patient presented to the emergency department. He collapsed after experiencing pain over his right frontotemporal region followed by a seizure witnessed by his family. Magnetic Resonance Imaging of the brain displayed a diffuse enlargement and abnormal T2 weighted and FLAIR hyperintense signals in the diagnostic impressions described by the radiologist of the right temporoparietal region. Clinical Discussion: Liquefactive Multiple Sclerosis, also known as tumefactive multiple sclerosis or Marburg-type multiple sclerosis, is a rare subtype of the neurological disorder that can be difficult to diagnose. Unlike the traditional form of Multiple sclerosis (MS), Tumefactive multiple sclerosis (TMS) can present as a brain tumor and must be diagnosed with a biopsy rather than via magnetic resonance imaging (MRI) and clinical findings alone. Patients can typically present with headache, cognitive abnormalities, mental confusion, aphasia, apraxia, seizures, and weakness. Here, we discuss the presentation, disease diagnosis process and patient management. Conclusion: The patient was stabilized and discharged with a referral to the neurosurgery and neurology departments for outpatient consultation for future clinical management and treatment of their condition.

Expansion Properties of the Young Supernova Type Iax Remnant Pa 30 Revealed

The recently discovered Pa 30 nebula, the putative type Iax supernova remnant associated with the historical supernova of 1181 AD, shows puzzling characteristics that make it unique among known supernova remnants. In particular, Pa 30 exhibits a complex morphology, with a unique radial and filamentary structure, and it hosts a hot stellar remnant at its center, which displays oxygen-dominated, ultrafast winds. Because of the surviving stellar remnant and the lack of hydrogen and helium in its filaments, it has been suggested that Pa 30 is the product of a failed thermonuclear explosion in a near- or super-Chandrasekhar white dwarf, which created a subluminous transient, a rare subtype of the Ia class of supernovae called type Iax. We present here a detailed study of the 3D structure and velocities of a full radial section of the remnant. The Integral Field Unit observations, obtained with the new red channel of the Keck Cosmic Web Imager spectrograph, reveal that the ejecta are consistent with being ballistic, with velocities close to the free-expansion velocity. Additionally, we detect a large cavity inside the supernova remnant and a sharp inner edge to the filamentary structure, which coincides with the outer edge of a bright ring detected in infrared images. Finally, we detect a strong asymmetry in the amount of ejecta along the line of sight, which might hint at an asymmetric explosion. Our analysis provides strong confirmation that the explosion originated from SN 1181.

Differentiating MYCN-amplified RB1 wild-type retinoblastoma from biallelic RB1 mutant retinoblastoma using MR-based radiomics: a retrospective multicenter case–control study

MYCN-amplified RB1 wild-type (MYCNampRB1+/+) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCNampRB1+/+ from the most prevalent RB1-/- retinoblastoma using pretreatment MRI and radiomics. Ninety-eight unilateral retinoblastoma patients (19 MYCN cases and 79 matched controls) were included. Tumors on T2-weighted MR images were manually delineated and validated by experienced radiologists. Radiomics analysis extracted 120 features per tumor. Several combinations of feature selection methods, oversampling techniques and machine learning (ML) classifiers were evaluated in a repeated fivefold cross-validation machine learning pipeline to yield the best-performing prediction model for MYCN. The best model used univariate feature selection, data oversampling (duplicating MYCN cases), and logistic regression classifier, achieving a mean AUC of 0.78 (SD 0.12). SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCNampRB1+/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCNampRB1+/+ and RB1-/- retinoblastoma subtypes.

Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.

Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM. This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02). Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.

Lung enteric-type adenocarcinoma with gastric metastasis: a rare case report and literature review

Lung enteric-type adenocarcinoma (ETAC) is a rare subtype of non-small cell lung cancer (NSCLC), comprising approximately 0.6% of all primary lung adenocarcinomas. It is characterized by a tendency for early metastasis and a prognosis comparable to that of common lung adenocarcinoma. This case report described a patient with lung-ETAC who developed gastric metastasis. The patient underwent treatment with chemotherapy and a PD-1 inhibitor, resulting in disease remission with a progression-free survival (PFS) of 8 months. The follow-up time was 13 months. This case report was aimed to enhance understanding of the biological behavior of this rare tumor and provide insights into potential future treatment strategies.

Nomogram predicts cervical lymph node metastasis of pathological subtypes of papillary thyroid carcinoma.

Pathological subtypes of papillary thyroid carcinoma (PTC) are important factors in thyroid cancer. Some rare subtypes exhibit extensive lymph node metastasis. These pathological subtypes should receive more attention in clinical practice. Patients with different pathological subtypes of PTC were selected from the SEER database. Logistic regression, random forest, and bootstrap aggregating (bagging) methods were employed to screen for risk factors associated with cervical lymph node metastasis in the training cohort. A nomogram was established based on the model with the largest area under the curve (AUC) and evaluated using calibration curves. Decision curve analysis (DCA) was used to evaluate the clinical benefit to patients. The nomogram was validated in depth by 200 iterations of tenfold cross-validation. A total of 7,882 patients were included in the analysis, with 5,516 patients in the training group and 2,366 patients in the testing group. The logistic regression model achieved the highest AUC of 0.7396. Sex, age, race, extension (extrathyroidal extension), pathological type, and primary tumour size were identified as independent risk factors for cervical lymph node metastasis (p < 0.05). The calibration curve indicated that the model was well calibrated. DCA indicated that the nomogram model had good clinical practicability. In clinical practice, it is important to consider the pathological subtypes of PTC. The established nomogram can serve as a predictive tool for assessing cervical lymph node metastasis.

Delayed Surgical Management of a Giant Rhabdomyomatous Meningioma: A Case Report

Background and Importance: Rhomboid meningioma (RM) is one of the rare and aggressive types of meningioma, typically classified as a central nervous system grade III anaplastic meningioma by WHO. In this report, we present an unusual case of RM. Case Presentation: The patient was a 67-year-old man, living in Kermanshah City, Iran. He came to a neurosurgery clinic with a chief complaint of a huge and unusual mass on his skull. Following the brain computed tomography scan and magnetic resonance imaging, the diagnosis of meningioma was considered. The patient underwent surgical intervention for the excision of the mass. Immunohistochemical findings demonstrated the diagnosis of RM (WHO grade III). Conclusion: RM is a rare and aggressive subtype of meningiomas with a high growth rate and poor prognosis. Early diagnosis and treatment especially in invasive ones can prevent many unpleasant and critical complications; although tumor location has a pivotal role in determining treatment strategy.

Primary Large-Cell Neuroendocrine Carcinoma of the Breast

Breast neuroendocrine carcinoma (NECB) is a rare type of breast tumor. Large-cell neuroendocrine carcinomas of the breast (LCNECB) are a special and rare histological subtype of NECB. Here, we present a case of a 59-year-old woman who was diagnosed with an LCNECB. A mass in the upper outer quadrant of the right breast was revealed via imaging. A histological examination showed the tumor cells were composed of clusters of large cells with obvious atypia that were polygonal or irregularly shaped. The patient underwent a right-breast-conserving radical surgery and sentinel lymph node biopsy (SLB). A histopathological examination revealed that the tumor of the right breast was 2.5 × 2 cm in size with vascular invasion, and the sentinel lymph node was negative. The immunohistochemical results showed that the tumor cells were diffuse and positive for chromogranin A (CgA), synaptophysin (Syn), and INSM1. The patient successfully completed chemotherapy and radiotherapy and is currently undergoing endocrine therapy.

Carotid artery stenting for symptomatic carotid near occlusions: Feasibility, safety and outcome analysis.

Extracranial internal carotid stenosis (EICS) is a well-established cause of stroke. Carotid near-occlusion (CNO), either distally collapsed or not, is a rare sub-type of EICS with conflicting data regarding the necessity for treatment. The aim of this study is to evaluate the results of carotid artery stenting (CAS) for patients with symptomatic CNOs. Institutional review board (I06-420-23) approval was obtained for this retrospective study. Consecutive data from January 2019 to January 2023 was obtained. Sixty-five patients underwent 66 procedures for symptomatic CNOs. Diagnosis of CNOs were made with DSA images. Treatment decisions were made by a multidisciplinary team. Patient data including age, gender, clinical presentation, affected side, complications (initial/ follow-up), and pre and post mRS scores were recorded and analyzed. There were 22 female and 43 male patients with symptomatic CNOs (mean age: 71.52 ± 9.32 years). The mean time from symptom-to-treatment was 3.91 weeks ± 3.74 weeks (ranging from 0 to 20 weeks). There were eight events recorded in the 30 days period after CAS; five (7.7%) were cerebral hyperperfusion syndrome (one causing haemorrhage) and three (4.5%) ischemic complications. Permanent neurologic deficit rate was 6% and 61 patients (94%) mRS scores were unchanged during last follow-up. Mean follow-up period was 22.94 ± 16.67 months (ranging from 0.5 to 60 months). Our study demonstrated that in the complex population of patients with symptomatic CNOs, CAS is a feasible option with acceptable rate of permanent neurologic deficits. Further studies are needed to assess its safety and long-term efficacy.

Identification of a novel variant in the LAMB3 gene in a patient with a distinct junctional epidermolysis bullosa laryngo-onycho-cutaneous syndrome phenotype.

Junctional epidermolysis bullosa (JEB) represents a rare mechanobullous genodermatosis, characterized by fragility and blister formation of the skin and mucous membranes. Within the JEB spectrum, laryngo-onycho-cutaneous (LOC) syndrome is a rare subtype that manifests with excess granulation tissue of the eyes, nails, skin, and larynx. Thus far, the LOC subtype has been linked predominantly to mutations in LAMA3, disrupting the epidermal basement membrane zone. We present a unique case of a congenitally affected female with numerous cutaneous eroded plaques, oral ulcers, nail dystrophy, and laryngeal involvement phenotypically consistent with the rare JEB LOC subtype. Genetic testing revealed a previously unreported homozygous variant in the LAMB3 gene (p.C316Y) highlighting a novel variant in the LAMB3 gene and its association with the LOC phenotype of JEB.

Solid-basaloid Variant of Mammary Adenoid Cystic Carcinoma – Report of an Unusual Case with Literature Review

Abstract Introduction/Objective Adenoid cystic carcinoma (AdCC) of breast is a rare subtype of malignancy, constituting approximately 0.1% of all breast carcinomas. The solid-basaloid variant (SB-AdCC) is exceedingly uncommon. Here, we present such an unusual case of SB-AdCC. Methods/Case Report A 64-year-old woman who underwent screening mammography presented with abnormal findings, revealing a hypoechoic ovoid, lobulated nodule at 7:00 of the left breast, which prompted an ultrasound- guided biopsy. Histologically, the biopsy cores demonstrated a 9 mm infiltrative round, solid nests with focal “cribriforming” areas. It was composed of monomorphic basaloid epithelial cells with marked nuclear atypia and high mitotic count. High-grade ductal carcinoma in situ, solid papillary carcinoma, and nonspecific invasive carcinoma were in differentials. Immunohistochemical (IHC) staining expressed positivity for CD117 and CK 5/6, while p63, SMMHC, and synaptophysin were negative. MYB gene rearrangement confirmed by fluorescence in situ hybridization. As expected, the tumor lacked ER, PR, and HER2 expression by IHC. Left breast mastectomy and axillary lymph node dissection have been scheduled. Results (if a Case Study enter NA) NA Conclusion Per literature review, the mean age of SB-AdCC at diagnosis was 68 years (33-84 years) with an average tumor size of 25 mm (12-70 mm). It had more aggressive behavior, with a higher propensity for lymph node metastasis, locally recurrence, and distant metastasis. The median disease-free survival was 46.5 months versus 151.8 months in those with class AdCC. Notably, neovascularization has emerged as a strong independent predictor of outcome in SB-AdCC. Most patients were treated with surgical excision, axillary lymph node dissection, and/or adjuvant chemotherapy. Limited studies demonstrated that neoadjuvant chemotherapy may induce an excellent response. Furthermore, a distinct molecular mutation enriched in NOTCH and CREBBP genes has been identified, which could be novel potential therapeutic target. Thus, awareness of this extremely rare breast cancer subtype and accurate differentiation from other entities are paramount for appropriate management strategies.

A Case Series of a Rare Parotid Gland Oncocytic Mucoepidermoid Carcinoma

Abstract Introduction/Objective We analyzed two cases of oncocytic mucoepidermoid carcinoma (OMEC) of the parotid gland which highlight the diagnostic challenges of oncocytic salivary gland neoplasms. OMEC’s are a rare type of salivary gland tumor commonly arising from the parotid gland that can easily be mistaken as benign. Proper pathologic diagnosis of these masses is critical, as it guides therapeutic intervention and has prognostic significance. Methods/Case Report In this case series, two patients were analyzed retrospectively for unilateral parotid masses. Results (if a Case Study enter NA) In a 67-year-old female, an MRI and biopsy were performed. Only a differential diagnosis could be provided, which favored oncocytoma or oncocytic carcinoma. Due to this uncertainty, a complete excision of the mass was performed. Considering the cytomorphology, immunohistochemistry (CK5/6 and P63 in oncocytes), and mucicarmine special stain highlighting scattered mucocytes, the patient was diagnosed with a low- grade OMEC. In our second case, an 80-year-old female, FNA of a posterior left ear mass 1 year prior revealed a low- grade oncocytic proliferation. With the presence of a left parotid mass one year later, additional imaging was performed and showed increased T2 hyperintensity on MRI, which caused concern for the clinicians. A superficial limited parotidectomy was performed and a differential of oncocytoma versus oncocytic variant of mucoepidermoid carcinoma was rendered. Further tumor characterization with fluorescence in situ hybridization (FISH) demonstrated a MAML2 translocation which guided diagnosis of OMEC. Conclusion With approximately 30% of all malignant salivary gland tumors being constituted by mucoepidermoid carcinoma, the ability to accurately diagnose even this rare subtype, oncocytic mucoepidermoid carcinoma, is of significant importance and relevance to pathologists in many practice settings. Herein we demonstrate the utility of H&amp;E morphology, immunohistochemistry, and MAML2 FISH in diagnosing OMEC in the setting of oncocytic salivary gland lesions. Future avenues, including tumor molecular profiling, will aid in elucidating clinicopathologic characteristics of this entity.

Synchronous endometrial and minor salivary gland carcinomas – role of molecular diagnostics amid lack of clinical suspicion

Abstract Introduction/Objective Synchronous malignancies account for 3-5% of all tumor diagnoses but can be challenging to detect if one or both tumors are rare histologic subtypes and clinical suspicion is lacking. Molecular diagnostics are critical for accurate diagnosis in these difficult cases to guide appropriate patient care. Methods/Case Report We report the case of a 49-year-old female who was diagnosed with a high-grade, mixed- histology endometrial adenocarcinoma a few years back. She was found to have hilar and mediastinal nodal carcinoma of uncertain differentiation a couple of months after her initial diagnosis, clinically labelled as metastatic endometrial carcinoma. Following neoadjuvant chemotherapy, her hysterectomy showed complete pathologic response, and was found to be POLE ultramutated on NGS. Follow-up PET scan in 2023 showed progression of hilar/endobronchial thickening, as well as interval increase in size of mediastinal nodes, again presumed to be endometrial metastases, despite the POLE mutant status. Repeat sampling was performed from both the sites, along with comprehensive molecular profiling. Cytology from the nodes and surgical pathology from the endobronchial lesion showed similar morphology consisting of hyperchromatic basaloid cells in cribriform arrangement with tubular structures containing myxoid stromal material, negative for PAX-8, ER, p40, and TTF1 immunostains, inconsistent with endometrial metastasis. Molecular studies including FISH and NGS showed MYB1::NFIB fusion characteristic of adenoid cystic carcinoma and absence of POLE mutation, definitively refuting the clinically suspected progression of endometrial metastasis. Molecular testing confirmed that the endobronchial tumor and mediastinal nodal involvement were caused by a second primary, distinct from her POLE-ultramutated endometrial carcinoma which disappeared with chemotherapy. Her extended molecular workup also revealed a pathogenic mutation in BRIP1, suggesting a genetic cancer predisposition syndrome requiring referral for genetic counseling. Results (if a Case Study enter NA) NA Conclusion Molecular pathology is an invaluable tool for unravelling diagnostic complexity. Pathologists must integrate cytomorphology, molecular genetics and knowledge of cancer biology to steer the clinical teams towards the best patient care.

Case Report : Undifferentiated Synovial Sarcoma Presenting as a Large Thoracic Mass: A Rare and Challenging Diagnosis

Background: Undifferentiated synovial sarcoma (USS) is a rare and aggressive subtype of soft tissue sarcoma. Its presentation as a large thoracic mass poses significant diagnostic and therapeutic challenges.  Case Presentation: A 34-year-old male presented with a three-month history of progressive chest pain and hemoptysis. Imaging studies revealed a large, cystic thoracic mass with pleural effusion. Initial serological testing suggested hydatid cyst, but subsequent testing revealed negative Echinococcus (Hydatid) IgG antibodies.  Diagnostic and Therapeutic Interventions: Repeat fine-needle aspiration cytology (FNAC) was deferred due to revised ultrasound findings indicating a solid fibrocystic vascular lesion. Bronchial artery embolization (BAE) was performed to control life- threatening hemorrhage. Thoracotomy and en-bloc mass excision were subsequently undertaken.  Histopathological Diagnosis: Histopathological examination of the resected specimen revealed undifferentiated synovial sarcoma and spindle cell sarcoma.  Clinical Implications: This case highlights the importance of correlating imaging and serological findings, managing vascular complications, and the efficacy of BAE in controlling hemorrhage. The significance of thoracotomy and mass excision in achieving diagnostic clarity and therapeutic success is underscored.  Conclusion: Undifferentiated synovial sarcoma presenting as a large thoracic mass poses significant diagnostic and therapeutic challenges. A multidisciplinary approach, incorporating imaging, serological testing, and surgical intervention, is crucial for achieving optimal patient outcomes.

Malignant Rhabdoid Tumor masquerading as Neuroblastoma: A rare Case-report

Abstract Introduction/Objective Malignant rhabdoid tumors (MRT) predominantly impact infants and young children, typically occurring around the age of 15 months. While they can emerge from soft tissues throughout the body, but commonly initiate in the kidneys. Neuroblastoma-like characteristics are seldom observed within the varied phenotypes of malignant rhabdoid tumors. Here, we present an exceptionally rare and distinctive subtype of malignant rhabdoid tumor exhibiting features akin to neuroblastoma localized within the unusal parapharyngeal space. Methods/Case Report A 2-month-old female presented to the ED with an enlarging right cervical neck mass. The mother reported a one-week history of upper respiratory tract symptoms and noticed an enlarging mass of her right neck. CT reported a “parapharyngeal abscess with airway compression”. The patient was started on Augmentin with no significant improvement. Repeat CT with contrast demonstrated an enlarging rim-enhancing 3 cm mass involving the right parapharyngeal space, trachea, and right carotid arteries. Laryngoscopy and incisional biopsy of right neck lymph nodes demonstrated a high-grade malignancy with prominent nucleoli, high N/C ratio and scant cytoplasm. The tumor tested positive for CD 99, synaptophysin, and neurofilament, leading to the initial diagnosis of neuroblastoma. However, molecular analysis uncovered the loss of INI-1 on 22q11.2, prompting a reevaluation and a final diagnosis of MRT with neuroblastoma-like characteristics was made. Results (if a Case Study enter NA) NA Conclusion A range of tumors displaying distinct “rhabdoid” cytological features are collectively termed as malignant rhabdoid tumors (MRTs). Conventional immunohistochemistry (IHC) staining for CD99, synaptophysin, neurofilament, and myogenin might suggest neuroblastoma, Ewing sarcoma, or rhabdomyosarcoma. However, the absence of INI-1 expression provides a definitive diagnosis. INI-1 loss, a purported tumor suppressor gene located on chromosome 22q11.2, solidifies the tumor’s classification as malignant rhabdoid tumor (MRT). Additionally, a positive neurofilament stain in MRT is crucial for diagnostic and therapeutic assessments. This differentiation is vital, given the dismal prognosis of MRT with a 5-year survival rate of less than 10%.

Not All Therapy-Related Neoplasms are Myeloid: A Case Report of Rare B-ALL With t(5;14) Following Alkylating Agent Treatment

Abstract Introduction/Objective Most therapy-related hematologic neoplasms are myeloid (t-MN). Although not recognized as a distinct entity in the WHO classification of hematologic neoplasms, therapy-related acute lymphoblastic leukemia (t- ALL) cases have been previously reported. ALL incidence increases with any previous malignancy and is higher in those with previous treatment, supporting the concept of therapy-related ALL. B lymphoblastic leukemia/lymphoma (B- ALL) with t(5:14) is a rare subtype of the ALL (&amp;lt;1%) harboring a IL-3/IGH gene translocation. We present the first case of B-ALL with t(5;14) following treatment with alkylating agents for breast carcinoma. Methods/Case Report A 79-year-old female received docetaxel, carboplatin, trastuzumab, pertuzumab, Herceptin and radiotherapy for an invasive ductal breast carcinoma. Two years later, she developed progressive pancytopenia requiring a bone marrow biopsy. Results (if a Case Study enter NA) The bone marrow aspirate smears demonstrated B-ALL with 25% blasts, limited neutrophilic maturation, moderate erythroid dysplasia, and decreased megakaryocytes with occasional atypical forms. On the biopsy, atypical megakaryocytes and lymphoblasts were positive for TP53 immunohistochemical stain. On flow cytometry, blasts were positive for CD19, cCD79a, CD22, CD10, TdT, and HLA-DR and only 6% were positive for CD34. Next generation sequencing showed TP53 and NRAS mutation. Karyotyping revealed 46, XX, t (5;14) (q33; q13) and trisomy 21. Conclusion B-ALL with t (5;14); IGH/IL3 fusion has not been previously reported following treatment with alkylating agents. The presence of morphologic myeloid dysplasia developing after chemotherapy with alkylating agents support causality being therapy related rather than an independent process. The case expands the breadth of known therapy- related hematologic neoplasms and raises questions regarding the mechanisms of leukemogenesis.

An unusual liver tumor with challenging morphologic features and immunophenotype: A case report of metastatic HPV-driven basaloid anal squamous cell carcinoma

Abstract Introduction/Objective Basaloid squamous cell carcinoma (BSCC), a rare subtype of squamous cell carcinoma, occurs most commonly in esophagus, lungs, and head and neck. Anal BSCC is extremely rare and has a 10-20% rate of metastasis. High-risk HPV (HR-HPV) is the main causative agent. BSCC occurrence in an atypical site without a known primary tumor, and with atypical immunoprofile can be a diagnostic challenge. Methods/Case Report We report an 83-year-old female with history of breast carcinoma who presented for worsening chest pain. Imaging studies showed pulmonary nodules, 1.8 cm hepatic mass, and pelvic nodules. Liver biopsy showed infiltrating nests of carcinoma with solid and cribriform patterns and luminal necrosis. Some tumor nests had basaloid features with peripheral palisading. Tumor was positive for CK7 and pankeratin; and negative for ER, SOX10, GATA3, GCDFP-15 (Breast markers), CDX2 (GI marker), P63 and P40 (squamous markers), INSM1, Synaptophysin (Neuroendocrine) and TTF1 (lung adenocarcinoma). There was microfocal staining with CK20 and SATB2. Tumor morphology and immunophenotype were not entirely specific to the site of origin. Further search into patient’s medical history showed a recent anal mucosal biopsy revealing a high-grade squamous epithelial lesion with diffuse P16 reactivity. The slides for the anal lesion were reviewed and showed morphologic features similar to the liver biopsy. Additional studies showed both tumors were positive for HR-HPV ISH, P16 (diffuse), and CK5/6 (patchy); and negative for P63. The morphologic features and immunoprofile were supportive of metastasis from HPV-driven BSCC of anus. Subsequent PET Scan revealed a rectal/anal mass. Results (if a Case Study enter NA) NA Conclusion For tumors with unusual morphology and immunophenotype, complete medical history review, and communication with clinician are important tools in achieving correct diagnosis. HR-HPV ISH is a new tool that can be very useful in reaching correct diagnosis in metastatic anogenital or oropharyngeal squamous carcinomas with basaloid features.