Sialadenoma papilliferum-like intraductal papillary tumor with unveiling BRAF V600E and PIK3CA H1047R mutations: Case report with molecular analysis and literature review.

INTRODUCTION: Sialadenoma papilliferum (SP), a rare minor salivary gland tumor, shares morphological and genetic similarities with syringocystadenoma papilliferum. Recent studies have identified BRAF V600E or HRAS mutations in SP, suggesting its neoplastic nature. Despite being uncommon, SP poses diagnostic challenges due to its resemblance to other lesions like squamous papilloma. The emergence of sialadenoma papilliferum-like intraductal papillary tumor (SP-IPT) further complicates its classification, emphasizing the need for thorough investigation. CASE PRESENTATION: A 50-year-old male presented with a left palatal lesion histologically diagnosed as SP-IPT. Surgical resection revealed characteristic features, including papillary projections into cystically dilated ductal spaces. Immunohistochemistry confirmed positivity for pan-keratin AE1/AE3, cytokeratin 7, SOX10, and BRAF V600E. Whole-exome sequencing identified BRAF V600E and PIK3CA H1047R mutations. No recurrence was observed three months post-excision. DISCUSSION: SP-IPT's diagnostic complexity stems from its resemblance to SP without an exophytic papillary component. However, shared BRAF mutations suggest a close relationship between the two entities. Similarities with skin adnexal tumors underscore the importance of molecular markers in tumor classification. The identification of PIK3CA mutation in SP-IPT adds to its molecular diversity, warranting further investigation into its clinical significance. CONCLUSION: This study presents a case of SP-IPT with unique histological and molecular features, highlighting its diagnostic and therapeutic challenges. The co-occurrence of BRAF V600E and PIK3CA H1047R mutations suggests a distinct molecular profile in SP-IPT, necessitating further research to elucidate its biological behavior and clinical implications.

Ciliated Muconodular Papillary Tumors of the Lung Harboring STRN::ALK Fusion: Case Report and Review of the Literature.

Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor, typically occurring in middle-aged and elderly individuals. The molecular mutation spectrum of CMPT remains insufficiently explored. Commonly known driver gene alterations include KRAS, BRAF, EGFR, and ALK rearrangement. This report details the clinicopathological features of 2 patients presenting with CMPT as pulmonary nodules during clinical examinations. Microscopic analysis revealed tumors with glandular or papillary structures, consisting of mucinous cells, ciliated columnar cells, and basal cells. Notably, both patients exhibited STRN::ALK fusion, a finding not previously associated with CMPT. STRN::ALK fusion serves as a target for therapy in various tumors, including non-small cell lung cancer, thyroid cancer, and colon cancer. Consequently, we conducted a review of relevant literature, summarizing the clinicopathological and molecular characteristics of CMPT to facilitate further research. Our insights enhance the understanding of this uncommon tumor and contribute to the expansion of its molecular alteration spectrum.

[Papillary renal neoplasm with reverse polarity]. / Papillyarnaya opukhol' pochki s reversivnoi polyarnost'yu yader.

Papillary renal neoplasm with reverse polarity is a rare subtype of papillary renal cell tumors with unique morphology, specific molecular features and good prognosis. The article presents literature data and describes our own observation of a papillary kidney tumor with reverse nuclear polarity in a 73-year-old patient. The difficulties of preoperative diagnosis of a tumor are shown, histological and immunohistochemical criteria for diagnosis and differential diagnosis of this tumor with other kidney tumors are presented. This rare case is of interest for both pathologists and clinicians.

Neurogenic Monodermal Teratoma in the Scapula of a Child: A Case Report.

Background: Neurogenic monodermal teratomas (NMTs) have been reported in the ovaries but not from bone. Case Report: A 6-year-old girl had an incidentally discovered lesion in the right scapula. Upon removal, it was an NMT with predominant choroid plexus. The disease had not progressed for 31 months. Conclusion: Neurogenic monodermal teratomas can also occur in bone.

Multiple bronchiolar adenomas/ciliated muconodular papillary tumors of the bilateral lung with tumor budding and potential malignant transformation into squamous cell carcinoma: a case report and literature review.

Background: Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is a rare lung tumor characterized by ciliated, mucous and basal cells. Recently, some cases of driver mutations or malignant transformations have been reported. However, the nature of BA/CMPT remains controversial. Here, we report a case of bilateral pulmonary multiple BAs with tumor budding and squamous metaplasia. Case Description: A 55-year-old man presented with multiple small nodules in the lower lobes of the bilateral lungs on physical examination 7 years prior. During the past 3 years of regular follow-up, some nodules had slightly enlarged. Because the nodules were mostly solid, the patient underwent video-assisted thoracoscopic segmentectomy of the left lower lung. A postoperative pathological diagnosis of BA was made. In all lesions, the fusion and mutation of major driver genes were not detected by next-generation sequencing (NGS). No recurrence or metastasis was observed after 37 months of follow-up. Notably, all five resected lesions were BA/CMPT, and one lesion was accompanied by squamous metaplasia and tumor budding. Conclusions: Our report found that BA/CMPT with squamous metaplasia and tumor budding has the potential to transform into lung squamous cell carcinoma, expanding its connection with malignant transformation. Smoking may be one of the risk factors. We also found that BA/CMPT can be multiple lesions rather than a solitary lesion.

Two tumors with combined features of bronchiolar adenoma/ciliated muconodular papillary tumor and sclerosing pneumocytoma.

OBJECTIVES: Bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) and sclerosing pneumocytoma (SP) are both rare and morphologically unique peripheral lung tumors with indolent behavior. These tumors have not been previously described as showing overlapping morphologic features and are generally genetically distinct. METHODS: Two cases were recently encountered that show hybrid morphologic features between BA/CMPT and SP, and the morphology and immunophenotype are described in detail. RESULTS: Both cases showed interstitial round cells typical of SP (TTF1+, EMA+), as well as areas more typical of BA/CMPT. One case showed BRAFV600E expression in the BA/CMPT areas but not in the SP-like cells. CONCLUSIONS: Although it is possible that these cases represent collision tumors or are examples of unusual metaplastic epithelial changes in SP, they also raise the possibility that these 2 entities could occasionally coexist in true hybrid tumors.

Agenesis of Dorsal Pancreas and Solid Pseudopapillary Tumor: Ventral Pancreas Preserving Portal Vein Resection and Reconstruction Using a Peritoneal Graft.

A diabetic lady in her 40s was referred to surgical oncologists with epigastric pain associated with vomiting. Computed Tomography (CT) Abdomen with contrast demonstrated a mass arising from the head of the pancreas with the absence of dorsal pancreas, confirmed on magnetic resonance cholangio-pancreatography (MRCP). A core needle biopsy was done, and the tumor was revealed to be a solid pseudopapillary epithelial neoplasm. She underwent sub-total pancreatectomy preserving the duodenum and ventral pancreas as there was adequate free margin; however due to the tumor abutting the anterior wall of the portal vein, it was resected, and reconstruction was done using a peritoneal graft. The patient made a good recovery without any significant post-operative events.

Computed tomography (CT) characteristics and pathologic basis of ciliated muconodular papillary tumors of the lung.

Background: Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor with papillary architecture. Most studies have focused on the clinicopathological features of CMPT, while computed tomography (CT) characteristics have rarely been systematically described. Methods: A cohort of 27 patients with surgically resected CMPT were identified. Clinical and demographic features were recorded. Preoperative CT images of the CMPTs and the corresponding histopathological basis were also retrospectively analyzed. Results: All of the tumors appeared as solitary nodules. Pure ground glass, part-solid nodules and solid nodules were detected in 2/27 (7.4%), 17/27 (63.0%), and 8/27 (29.6%) patients, respectively. Twenty-one tumors (77.8%) were located in the lower lobe. The average tumor size was 1.21±0.74 (range, 0.44-3.46) cm. Eighteen (66.7%) of the 27 patients had tumors with well-defined margins and lobulated contours. Fifteen patients (55.6%) had air bronchograms in the tumor, and 19 patients (70.4%) had air-containing space. There were two patients whose tumor size was enlarged and accompanied by an increase in solid components, and one patient simply had an increase in tumor size at the preoperative follow-up duration. Notably, one patient with solid tumor components was finally diagnosed with CMPT accompanied by adenocarcinoma. Conclusions: CMPTs of the lung mostly manifest as solitary, lobulated, well-defined tumors with air-containing spaces on CT and often occur in the periphery of the pulmonary lower lobe. When CT findings meet these criteria, the possibility of CMPT should be considered. Additionally, CMPT can coexist with adenocarcinoma. Further investigation will contribute significantly to the biological properties of CMPT and its relationship to the potential for malignant transformation.

Mucous Gland Adenoma of the Lung: A Neoplastic Counterpart of Mucinous Bronchial Glands.

Mucous gland adenoma (MGA) is a rare benign tumor that usually arises in the proximal airway and consists of mucus-secreting cells resembling bronchial glands. Here, we report 2 cases of MGAs and describe their morphologic, immunohistochemical, and molecular profiles in comparison with 19 pulmonary tumors of 5 other histologic types with mucinous cells (invasive mucinous adenocarcinoma, mucoepidermoid carcinoma, mixed squamous cell and glandular papilloma, bronchiolar adenoma/ciliated muconodular papillary tumor, and sialadenoma papilliferum). Two MGAs were found in 1 male patient and 1 female patient, located in the bronchus and trachea, respectively. One MGA was examined by RNA sequencing, and no putative driver mutations (including BRAF, KRAS, and AKT1 mutations) or gene fusions were identified. In another case of MGA, V600E mutations of BRAF and E17K mutations of AKT1 were not detected by allele-specific real-time PCR or digital PCR, respectively. However, a gene expression analysis revealed that the MGA presented a specific RNA expression profile with multiple genes enriched in the salivary gland. The gene expression of NKX3.1 was significantly higher in the MGA case in comparison to normal control lungs (P < .001). We then examined NKX3.1 immunohistochemistry for 2 MGAs and 19 tumors of 5 other histologic types. NKX3.1 was positive in MGA (2/2, 100%), whereas all constituent cells, including mucinous cells, were negative for NKX3.1 in other histologic types (0%, 0/19). In normal lung tissue, NKX3.1 was positive for mucinous acinar cells of the bronchial glands. In conclusion, the gene expression profile, taken together with the histologic similarity between MGA and bronchial glands, and the preferred location of the tumors (proximal airways with submucosal glands) suggest that MGA is a neoplastic counterpart of mucinous bronchial glands. NKX3.1 immunohistochemistry can be a sensitive and specific ancillary marker that distinguishes MGA from other histologic mimics.

An Unusual Finding: Papillary Tumor of the Pineal Region.

A papillary tumor of the pineal region (PTPR) is a rare tumor of neuroepithelial origin formed from specialized ependymocytes of the subcommissural organ located in the lining of the posterior commissure, not the pineal gland itself. Patients with this type of tumor generally present with nonspecific symptoms secondary to obstructive hydrocephalus such as headache and vision changes. The mean age of patient presentation is 31, with a slight predominance in females. This type of tumor has a high rate of recurrence (56%) following surgical resection. This case study describes the presentation of this uncommon tumor in a 61-year-old woman, including presentation, imaging, surgery, and pathology findings.

Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma.

Ciliated muconodular papillary tumor/bronchiolar adenoma (CMPT/BA) is a recently introduced benign lung tumor. It remains unclear whether CMPT/BA is associated with a specific type of lung cancer (LC). We studied the clinicopathological characteristics and genetic profiles of the coexisting primary LC and CMPT/BA (LCCM) cases. We identified eight LCCM (0.4%) from the resected Stage 0-III primary LC (n = 1945). The LCCM cohort was male-dominant (n = 8), elderly (median 72 years old), and most were smokers (n = 6). In addition to the adenocarcinoma (n = 8), we detected two squamous cell carcinomas and one small cell carcinoma-in some cases, multiple cancer. The target sequence/whole exome sequence (WES) revealed no shared mutations between CMPT/BA and LC. One exceptional case was invasive mucinous adenocarcinoma harboring an HRAS mutation (I46N, c.137T>A), but it was likely to be a single nucleotide polymorphism based on variant allele frequency (VAF). Other driver mutations in LC included EGFR (InDel, n = 2), BRAF(V600E) (n = 1), KRAS (n = 2), GNAS (n = 1), and TP53 (n = 2). BRAF(V600E) was the most frequent mutation in CMPT/BA (60%). In contrast, LC showed no specific trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation profiles of CMPT/BA and LC in coexisting cases, suggesting mostly independent clonal tumorigenesis of CMPT/BA from LC.

Bronchiolar adenoma/ciliated muconodular papillary tumor mixed with adenocarcinoma in situ in the same tumor.

Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is defined as a benign tumor composed of epithelial and basal cells. Recently, some cases with driver mutations or malignant transformation have been observed. Thus, whether BA/CMPT is benign or malignant remains controversial. We herein report an extremely rare case of a 68-year-old woman with a CMPT accompanied by adenocarcinoma in situ (AIS). BA/CMPT existed inside the AIS. The BA/CMPT component did not show any driver mutations; however, the AIS component had an EGFR driver mutation in exon 19. The accumulation of cases and further studies are needed to discuss the malignant potential of BA/CMPT.

Solid Pseudopapillary Neoplasm of the Pancreas: A Clinicopathological Study of 12 Cases With Emphasis on Diagnostic Pitfalls.

INTRODUCTION: Solid pseudopapillary neoplasm of the pancreas (SPNP) is a rare primary neoplasm with distinct clinicopathological features. The tumor most commonly occurs in younger (premenopausal) women and is typified by low malignant potential and an excellent overall prognosis. METHODS: A retrospective search over 20 years at two referral tertiary care institutions (King Faisal Hospital and Research Center and King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia) revealed 12 female patients diagnosed with SPNPs. The reslts of ancillary studies performed at the time of diagnosis were also reviewed and placed in the context of current recommendations. RESULTS: The clinical and pathological findings were reviewed. All patients were females, aged 18 to 30 years. Eight patients presented with abdominal pain, of which two experienced significant weight loss, and four presented with abdominal mass/discomfort. The tumor size ranged from 1.5 and 15 cm. Two cases were initially diagnosed as neuroendocrine tumors (NETs). One of the cases presented as a multifocal disease. All patients were treated surgically with a follow-up period between one and 11 years. Only one patient presented with peritoneal metastasis after seven years of follow-up, but generally, all are doing well. CONCLUSIONS: We have analyzed 12 SPNP cases in our population over 20 years (2001-2021) in this study. In brief, SPNP is a low-grade malignant potential tumor. Even though SPNP is a recognized entity, diagnostic challenges can arise particularly in the setting of limited sampling. Pathologists must be aware of the classic morphological features of SPNP and the characteristic profile of immunohistochemistry and be able to differentiate SPNP from other mimickers, especially well-differentiated NETs of the pancreas, and ultimately to avoid misdiagnosis and unnecessary oncologic treatment. Adequate surgical resection with negative margins is associated with an excellent outcome.

Does Bladder Cancer with Inchworm Sign Indicate Better Prognosis after TURBT?

Background: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer (NMIBC). Nevertheless, pathologically diagnosed muscle invasive bladder cancers (MIBCs) are occasionally diagnosed from tissue obtained by transurethral resection of bladder tumor (TURBT) in patients with inchworm sign. Methods: We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following TURBT. Results: Of the 109 patients with inchworm sign, 94 (86.2%) and 15 (13.8%) were NMIBC and MIBC, respectively. Non-papillary tumors (hazard ratio (HR): 9.55, 95% confidence interval (CI): 2.07−44.10; p < 0.01) and tumors located in the bladder neck (HR: 7.73, 95% CI: 1.83−32.76; p < 0.01) were significant predictors of MIBC in bladder cancer with inchworm sign. Furthermore, recurrence-free survival (RFS) and progression-free survival were compared between patients with NMIBC with and without inchworm sign; however, no significant differences were found. In patients with NMIBC with inchworm sign, positive urine cytology was a prognostic factor for RFS (HR: 1.90, 95% CI: 1.04−3.48; p = 0.04). Conclusions: In bladder cancer with inchworm sign, 86.2% were NMIBC. Even in the case of inchworm sign, the presence of a non-papillary tumor or a bladder neck tumor before TURBT should be noted because of the possibility of MIBC. In this study, the inchworm sign was not a prognostic factor in patients with NMIBC.

Papillary tumor of the pineal region in pediatric patient - A case report.

Background: Papillary tumor of the pineal region (PTPR) represents a rare and histologically distinct subgroup of tumors originating in the pineal region. Few pediatric cases have been reported so far in the literature; therefore, clinical data are scarce. Case Description: We describe a case of PTPR in a 9-year-old girl who presented with a 5-month history of excessive appetite and weight gain. The patient underwent neuroimaging procedures and total gross surgical resection with postoperative adjuvant local radiotherapy, which from our experience was the best treatment choice as an attempt to avoid local recurrence. During 78-month follow-up, the patient from our study manifested no disease recurrence. Conclusion: PTPR should be included in the differential diagnosis of pineal region masses.

Low-Grade Ovarian Stromal Tumors with Genetic Alterations of the Wnt/ß-Catenin Pathway That Is Crucial in Ovarian Follicle Development and Regulation.

The Wnt signaling pathway is important in the normal development and regulation of ovarian follicles throughout the lifecycle of females. Dysregulation of the Wnt signaling pathway, genetically or epigenetically, with subsequent activation of ß-catenin has been implicated in tumorigenesis of a spectrum of ovarian neoplasms, from benign to malignant. We review the recent findings of the Wnt signaling pathway involved in regulating normal physiologic processes of the ovarian follicle cycle. We also review the ß-catenin mutations in a family of low-grade ovarian stromal tumors, focusing on characterizing their shared morphological features and the utility of immunohistochemistry of ß-catenin in facilitating the accurate diagnosis of these ovarian stromal tumors. The Wnt signaling pathway is one of the most critical mechanisms in regulating cell proliferation, differentiation, and morphogenesis. The Wnt signaling pathway comprises a diverse group of glycoproteins that serve as ligands and bind to transmembrane Frizzled family receptors. The ligand-receptor interactions activate the pathway and govern the downstream signaling cascades, ultimately affecting the transcriptional control of the cellular cytoskeleton, organelle dynamics, epithelial-mesenchymal interaction, and tissue remodeling in the ovary. Wnt signaling consists of two major pathways: a canonical pathway that is ß-catenin-dependent and a non-canonical Wnt pathway that is ß-catenin-independent. Canonical Wnt signaling is governed by the interaction of ß-catenin with other molecules to regulate cellular decisions related to proliferation and differentiation. Recent studies have demonstrated that the Wnt signaling pathway plays important roles in the development and regulation of ovarian folliculogenesis and oogenesis.

Ethanol Ablation as a Treatment in a Low-Risk Follicular Thyroid Cancer: A Case Report.

Thyroid nodules are relatively prevalent in clinical practice; they are found by palpation in 3-7% of the general population and by ultrasonography (US) in roughly 50%. Image-guided nonsurgical procedures such as ethanol ablation (EA) or radiofrequency ablation (RFA) have been proposed for a selected group of patients as alternatives to traditional treatments. We present a case of a low-risk follicular variant of papillary thyroid cancer treated successfully with EA after examination and identification of the nodule as an ideal candidate for the treatment proposed. We highlight the efficacy of EA in this case, and how this contributes to the existing literature to continue proposing this as a viable treatment option.

Bronchiolar adenoma with unusual presentation: Two case reports.

BACKGROUND: The clinicopathological features, immunohistochemical characteristics, and genetic mutation profile of two unusual cases of distal bronchiolar adenoma are retrospectively analyzed and the relevant literature is reviewed. CASE SUMMARY: Case 1 was a 63-year-old female patient who had a mixed ground-glass nodule, with mild cells in morphology, visible cilia, and bilayer structures in focal areas. Immunohistochemical staining for P63 and cytokeratin (CK)5/6 revealed the lack of a continuous bilayer structure in most areas, and no mutations were found in epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, Kirsten rat sarcoma, PIK3CA, BRAF, human epidermal growth factor receptor-2 (HER2), RET, and neuroblastoma RAS genes. Case 2 was a 58-year-old female patient who presented with a solid nodule, in which most cells were observed to be medium sized, the nuclear chromatin was pale and homogeneous, local cells had atypia, and cilia were found locally. Immunohistochemical staining for P63 and CK5/6 showed no expression of these proteins in mild cell morphology whereas the heteromorphic cells showed a bilayer structure. The same nine genes as above were analyzed, and HER2 gene mutation was identified. CONCLUSION: Some unresolved questions remain to be answered to determine whether the lesion is a benign adenoma or a part of the process of malignant transformation from benign adenoma of the bronchial epithelium. Furthermore, whether lesions with atypical bilayer structures are similar to atypical hyperplastic lesions of the breast remains to be elucidated. Moreover, clarity on whether these lesions can be called atypical bronchiolar adenoma and whether they are invasive precursor lesions is needed. Future studies should examine the diagnostic significance of HER2 gene mutation as a prognostic indicator.

Mucin distribution in bronchiolar adenoma/ciliated muconodular papillary tumor reveals organoid differentiation simulating the normal lung.

Bronchiolar adenoma/ciliated muconodular papillary tumor is a lung neoplasm exhibiting various degrees of proximal and distal bronchiolar differentiation. Here, we evaluated distribution of MUC5AC and MUC5B in bronchiolar adenoma/ciliated muconodular papillary tumor for comparison with that seen in normal respiratory tract. In normal respiratory tract, MUC5AC was mainly distributed in large bronchi, while MUC5B was distributed in bronchi, bronchioles, and submucosal glands. In bronchiolar adenoma/ciliated muconodular papillary tumor, MUC5AC was primarily distributed in luminal cells of large airspaces, and MUC5B was distributed in luminal cells of small airspaces and mucinous glands, in addition to large airspaces, regardless of distal or proximal differentiation. In particular, MUC5B was distributed in non-mucinous club and ciliated cells in both the normal respiratory tract and bronchiolar adenoma/ciliated muconodular papillary tumor. These results indicate that MUC5AC and MUC5B distribution in bronchiolar adenoma/ciliated muconodular papillary tumor is similar to that seen in normal respiratory tract, suggestive of organoid differentiation simulating the normal lung.