Unique Histopathologic Features Research Articles

Trichofolliculoma - A Case Report.

Trichofolliculoma is a rare benign, hamartomatous adnexal tumour of the skin. Aetiology seems to be unclear. It is usually seen in adults, with no gender predilection. The most commonly involved sites are the face and scalp. It appears as a papule or nodule with small protruding hairs, which is a classic feature of the tumour. It has unique diagnostic and histopathological features that help in making a definitive diagnosis. Here, we report an exemplary case of an adult male patient aged 45 years with a gradual progressive diffuse swelling on the left side of the face for 1.5 years. Clinically, it was diagnosed as a sebaceous cyst, but after the biopsy histopathological evaluation was performed, and the diagnosis was confirmed as trichofolliculoma.

Chemoradiation Therapy as the Treatment of the Adenoide Cystic Cancer of the Bartholin Gland : About One Case Report and Review of the Literature

Adenoid cystic carcinoma (ACC) of the Bartholin's gland is a rare yet clinically significant malignancy Originating from the Bartholin's gland, situated in the vulvar region, ACC exhibits unique histopathological features and clinical behaviors. In our article, we describe a clinical case involving a 28-year-old female patient who initially presented with a painful swelling on the left labia majora. Initially misdiagnosed as simple Bartholin's gland inflammation, biopsy revealed cystic adenoid carcinoma of the Bartholin gland upon histopathological examination. Radiological evaluation revealed a locally advanced left vulvar lesion with no evidence of distant metastasis. Given the impracticability of surgical intervention, concurrent chemoradiation therapy was administered, resulting in favorable outcomes. ACC has been a diagnostic therapeutic challenge, there is currently no established therapeutic standard. Despite its infrequent occurrence, ACC warrants attention due to its potential for aggressive local invasion, distant metastasis, and propensity for recurrence.

ETMR-05. DEVELOPMENT OF NOVEL PRECLINICAL MODELS AND THERAPEUTIC STRATEGIES FOR ETMR

Abstract BACKGROUND Embryonal Tumor with Multilayered Rosettes (ETMR) is a very rare, aggressive pediatric brain tumor with a dismal 5-year overall survival rate. Few genetic aberrations in miRNA clusters and processing machinery have been detected in ETMRs with 90% of ETMR patients having the C19MC amplification. ETMRs show unique histopathological features which, together with the detection of C19MC or DICER alterations, are necessary for diagnosis. The cellular and molecular mechanisms underlying ETMR development are poorly understood, and targeted therapeutics have not been developed due to scarcity of preclinical models. To expand knowledge of ETMR biology and accelerate the design of novel and therapies, it is thus essential to develop preclinical models. METHODS We have generated two novel patient-derived ETMR cell lines from resected patient derived tumor samples (CTBP-03A and CBTP-139) and created three patient-derived xenograft (PDX) models (CTBP-03A, CBTP-139 and CBTP-38). We have used these unique patient-derived cell lines to identify mechanisms driving ETMR development and progression. To identify novel therapeutic targets, we conducted high-throughput drug screening (HTDS) utilizing 2480 approved and investigational drugs, against the CBTP-03A and CBTP-139 lines. RESULTS Among the candidate drugs showing an inhibitory effect on both lines, compounds were selected based on their activity, CNS penetration ability, mechanism of action, and bioavailability, if known. The top selected hits were screened in an all-versus-all format, totaling 1953 combinations. The rapidity of action and efficacy of the top choice compounds used as single agent or in double and triple combination was assessed by caspase glow and cell titer glow assays. This initial combination screen identified DNA replication stress, retinoid receptor agonist and FGF signaling as potential combinatorial targets. Data are currently being validated in vivo. CONCLUSIONS This is the first combinatorial HTDS on two novel patient-derived cell lines which highlighted potential drug combination strategies for the treatment of ETMR.

Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges.

FGFR3::TACC3 fusion is a driver, potentially targetable, genetic alteration identified in approximately 4% of high-grade diffuse gliomas and rare cases with low-grade histology. Herein, we review the genetic and epigenetic features of these tumors and highlight the challenges in their classification and grading. Diffuse gliomas with FGFR3::TACC3 fusion display unique histopathological and molecular features, including an oligodendroglioma-like appearance, calcifications, and CD34 extravascular immunoreactivity. High-grade tumors exhibit molecular alterations and a DNA methylation profile typical of glioblastoma, suggesting that they may represent a subtype clinically characterized by a slightly better prognosis. Tumors with low-grade morphology are genetically and epigenetically heterogeneous. Some, exclusive to adults, have molecular alterations typical of glioblastoma, although most do not match any methylation classes, using version 12.5 of the Heidelberg classifier. Another group, which mostly affects children or adolescents, lacks the molecular features of glioblastoma and has a DNA methylation profile similar to that of low-grade glioneuronal tumors. In conclusion, diffuse gliomas with FGFR3::TACC3 fusion do not constitute a distinct nosological entity, owing to their genetic and epigenetic diversity. Further studies are warranted to clarify the biological aggressiveness of tumors with low-grade histology to refine the grading and determine the optimal treatment strategy.

X-linked Alport syndrome presenting in mother and son with the same unique histopathological features

Alport syndrome has been linked to three different genes, that is, COL4A3, COL4A4 and COL4A5. It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with COL4A5-related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman’s capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and/or assemblies in Bowman’s capsule is more vulnerable to missense mutations in COL4A5 than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in COL4A-related disorders.

Plasma cell periodontitis: A rare disease entity with unique clinical and histopathological features

Abstract Plasmacytoid mucositis is a rare form of periodontal disease characterized by the infiltration of plasma cells into the gingival tissues. This case report highlights a unique case of plasmacytoid mucositis with periodontal involvement in a young woman. A 32-year-old female presented with gingival hyperplasia and cheilitis. The clinical examination revealed the presence of deep periodontal pockets, severe gingival inflammation, and bone loss. The patient was treated with a combination of nonsurgical periodontal therapy, systemic antibiotics, and oral hygiene instructions. After 2 months of the treatment, the patient showed significant improvement in the clinical parameters. This case report adds to the existing literature on this condition, emphasizing the importance of early diagnosis and prompt treatment. It highlights the need for a multidisciplinary approach involving periodontists, histopathologists, and microbiologists. The lesson to be learned from this case report is that plasmacytoid periodontitis should be considered and a biopsy should be performed to confirm the diagnosis.

Gingival Carcinoma Cuniculatum: A Case Series of Seven Cases with Emphasis on Immunohistochemical and Histochemical Features.

Oral carcinoma cuniculatum (CC) is a rare distinct variant of oral squamous cell carcinoma (OSCC) displaying unique clinical and histopathological features. CC is a locally aggressive malignancy with lower metastatic potential and has a tendency to invade the underlying bone yielding nonspecific clinical presentation resembling fungal/bacterial infections or osteomyelitis. Seven rare cases of gingival CC are reported with special emphasis on immunohistochemistry and special stains. Clinical and demographic profile were analysed and all cases were subjected to Ki-67 and p53 immunostaining and Ayoub-Shklar histochemical staining. For comparison, age and gender matched seven cases of conventional OSCC with bony involvement were recruited. IBM SPSS statistics software version 26 (IBM Analytics, Armonk, New York, U.S.) was used to analyse the data. All cases of CC lacked p53 expression in contrast to OSCC and demonstrated intermediate to high proliferation index in stroma also. The keratin staining and cytokeratin profile in OSCC and CC were also found to be statistically different. CC is a rare well differentiated variant of OSCC with different pathways involved in the pathogenesis. Local aggressive and invasive nature could be the result of unique interaction between epithelium and stromal elements. Oral health care provider must be familiar with this uncommon variant of OSCC.

The immunohistochemical expression Ki-67 In Polymorphous Low Grade Adenocarcinoma of the Salivary Glands

Background: Polymorphous Low Grade Adenocarcinoma is a rare malignant tumor of minor salivary glands. It has an unique histopathological, clinical and behavioural features. Most of its incidence has been presented in the palate. It shows a variety of growth patterns within the same one lesion, including cribriform, tubular, and solid areas that may mimic adenoid cystic carcinoma. The tumor cells histologically are characterized by lacking of nuclear atypical and hyperchromatism with rare mitoses. However, the prognosis of this tumor is good because of its low grade, although it has an unpredictable potential to metastasize.
 Objectives: To evaluate the histopathological expression of Ki-67 proliferation antigen in Polymorphous low grade adenocarcinoma and compare the results with the clinicopathological parameters and grading of the tumors.
 Materials and Methods: This study includes 20 cases with Polymorphous Low Grade Adenocarcinoma of minor salivary glands diagnosed histopathologically and treated surgically, were investigated for the immunohistochemical expression of Ki-67 antigen. Immunohistochemical staining was performed using a Labeled Strept- Avidin Biotin method (LSAB) and 0.05 (two-sided) was the level of significance.
 Results: Twenty cases of Polymorphous Low Grade Adenocarcinoma of salivary glands were histologically diagnosed in this retrospective study to evaluate the expression of Ki-67. The mean age for patients with PLGA was nearly (50.6). (12) (60%) cases were males and (8) (40%) cases were females and also male to female ratio was (1.5:1).
 In regarding to site distribution, the most common site was the palate followed by the submandibular gland and floor of the mouth. 
 Conclusions: it was observed that there is a higher rate of cellular proliferation in malignant tumors with high grade, indicating their role in the malignancy and aggressive behavior of these tumors.

The significance of T-BET-positive CD8 T-cells with diminished CD5 expression in Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare condition characterized by benign localized lymphadenopathy and clinical symptoms such as fever, sore throat, odynophagia, and leukopenia. Though the etiology of KFD is unknown, this condition is similar to viral infection, including increased infiltration of activated plasmacytoid dendritic cells. KFD exhibits three histological phases that reflect its progression status: proliferative, necrotic, and xanthomatous lesions. The expression loss of pan T-cell markers, such as CD2, CD5, and CD7, of infiltrating T-cells is observed in KFD cases, complicating the distinction from T-cell lymphoma. However, reports on the loss of their expression in KFD have been limited. Furthermore, the precise population of the T-cell subset in KFD is still unclear. Here, we focused on surface markers and transcription factors for T-cell differentiation and analyzed them immunohistochemically in 46 KFD cases. We observed diminished CD5 expression of CD8-positive (CD5dim CD8+) T-cells in the proliferative lesion of KFD cases. Furthermore, these CD5dim CD8+ T-cells expressed T-BET, a master regulator of type 1 helper T-cells. The upregulation of T-BET and downregulation of CD5 in CD8+ T-cells causes dysregulated activation and proliferation of CD8+ T-cells, potentially contributing to the unique histopathological features of KFD. Recognizing the frequent infiltration of T-BET-positive CD5dim CD8+ T-cells in KFD is important for distinguishing it from mature T-cell lymphoma. Our findings suggest that the immune response in KFD shares similarities with viral infections and highlight the importance of characterizing T-BET-positive CD5dim CD8+ T-cell populations for understanding KFD pathogenesis.

Low-Grade Gliomas: Histological Subtypes, Molecular Mechanisms, and Treatment Strategies.

Low-Grade Gliomas (LGGs) represent a diverse group of brain tumors originating from glial cells, characterized by their unique histopathological and molecular features. This article offers a comprehensive exploration of LGGs, shedding light on their subtypes, histological and molecular aspects. By delving into the World Health Organization's grading system, 5th edition, various specificities were added due to an in-depth understanding of emerging laboratory techniques, especially genomic analysis. Moreover, treatment modalities are extensively discussed. The degree of surgical resection should always be considered according to postoperative quality of life and cognitive status. Adjuvant therapies focused on chemotherapy and radiotherapy depend on tumor grading and invasiveness. In the current literature, emerging targeted molecular therapies are well discussed due to their succinctly therapeutic effect; in our article, those therapies are summarized based on posttreatment results and possible adverse effects. This review serves as a valuable resource for clinicians, researchers, and medical professionals aiming to deepen their knowledge on LGGs and enhance patient care.

Hibernoma mimicking a lipoma: A case report of a rare benign tumor

Hibernomas are rare, benign soft tissue tumors developed from fetal brown fat [1]. They account for around 1.6% of benign lipomatous tumors and present as progressive, slow-growing, painless subcutaneous masses [2]. Hibernomas resemble lipomas in their clinical behavior, but their unique imaging and histopathologic features may aid in differentiating them from each other [1]. We report a case of a 19-year-old Emirati woman who presented with painful lower back swelling for one year. The lesion was excised, and the histopathology revealed a diagnosis of hibernoma. The patient had an uneventful postoperative course and was discharged on the second postoperative day. The management approach of hibernomas varies as per the symptoms, our patient was managed with surgical intervention whereas asymptomatic patients can be observed. Surgical resection is the definitive treatment. No local recurrence has been reported.

A Translational Approach to Identifying and Targeting TNF Signaling in Idiopathic Multicentric Castleman Disease

Idiopathic multicentric Castleman disease (iMCD) is a rare, immunological illness with an unknown etiology. It is characterized by multiple enlarged lymph nodes with unique histopathological features and systemic inflammation resulting from cytokine release syndrome, which can rapidly develop into multiple organ failure and death. Inhibition of the pro-inflammatory cytokine interleukin-6 (IL-6) with siltuximab, the only FDA-approved therapy for iMCD, is an effective treatment for approximately one-half of patients. Patients who do not respond to IL-6 inhibition have few treatment options beyond cytotoxic chemotherapy. A better understanding of the pathogenic mechanisms underlying iMCD is critically needed to uncover new potential treatments for patients. To characterize the immune dysregulation in iMCD, our lab previously profiled serum analytes and circulating cell types in patient blood during active disease. Serum proteomic analyses identified tumor necrosis factor (TNF) signaling as a highly enriched pathway in both siltuximab responders and non-responders. Both immunophenotypic and serum proteomic data indicated that T cells, which can produce TNF, were activated in iMCD. However, whether TNF production by activated T cells was a key mechanism promoting iMCD was unclear. To determine if T cells contribute to the characteristic cytokine storm in iMCD, we investigated the ability of T cells from iMCD patients to produce different inflammatory cytokines including TNF. Upon stimulation with phorbol myristate acetate and ionomycin (PMA/I), both naïve and non-naïve CD4 + T cells from iMCD patients (n=9) produced significantly more TNF compared to healthy controls (n=9). There was a >2-fold increase in the frequency of TNF-expressing naïve CD4 + T cells from iMCD patients versus healthy controls. We also found a significant, yet marginal, increase in the frequency of TNF + non-naïve CD4 + T cells from iMCD patients. Although TNF and IFN-γ are both well-established markers of T cell activation, we did not observe a similar rise in interferon-gamma (IFN-γ) after stimulation in either CD4 + T cell subset. Taken together, these data indicate that CD4 + T cells in iMCD patients hyper-respond to stimulation specifically by producing excess TNF. In parallel to flow cytometric, proteomic, and T cell stimulation data, we leveraged KGML-xDTD, a knowledge graph-based machine learning framework, to predict potential novel drug treatments for iMCD. Utilizing 3,659,165 nodes and 18,291,237 edges in RTX-KG2 from 70 public biomedical sources, we trained a random forest-based machine learning algorithm on true positive and true negative treatment relationships. The top three novel predicted treatments for iMCD included two TNF inhibitors, adalimumab and certolizumab pegol, and the B cell depleting agent, rituximab, the second most prescribed drug for iMCD after siltuximab. We then used the reinforcement learning module of KGML-xDTD to predict the mechanism linking adalimumab to iMCD, which included IL-4, IL-6, IL-8, IL-10, STAT3, and CD4. These data reveal a potential new treatment strategy and further implicate TNF by CD4-expressing T cells in iMCD pathogenesis. In addition to our laboratory findings and predictive modeling data that suggest that TNF production by T cells promotes iMCD, we report the successful treatment of a highly refractory iMCD patient with off-label use of a TNF blocker. When a 50-year old iMCD patient was experiencing multi-organ system dysfunction and preparing for hospice care after not responding to IL-6 inhibition, IL-1 inhibition, Bruton's tyrosine kinase (BTK) inhibition, chemotherapy, and autologous stem cell transplantation, we initiated treatment with adalimumab alongside BTK inhibition. Within 3 days of the first infusion, the patient's symptoms and organ dysfunction began to improve and the patient has been in remission for over 6 months. We utilized a translational research approach including experimental and unbiased machine learning approaches to identify TNF as a novel therapeutic target that we inhibited to treat a highly refractory iMCD patient. Together, our data suggest that over-production of TNF, in part by activated T cells, promotes iMCD pathogenesis and highlight that further research is needed into TNF inhibition as a potential treatment strategy for iMCD.

Collision Tumour Comprising Desmoplastic Ameloblastoma and Squamous Odontogenic Tumour in the Anterior Maxilla: A Case Report.

Collision tumours, characterized by the simultaneous occurrence of two distinct neoplasms within the same anatomical site, are exceedingly rare in oral pathology. This case report presents an uncommon collision tumour involving desmoplastic ameloblastoma and squamous odontogenic tumour in the anterior maxilla of a 52-year-old male from the Indian population. Desmoplastic ameloblastoma is a variant of ameloblastoma known for its unique histopathological features, while squamous odontogenic tumour is a benign epithelial odontogenic tumour with distinctive clinical behaviour. The rarity of this occurrence emphasizes the need for accurate diagnosis and effective treatment strategies. This report discusses the clinical presentation, radiographic findings, and histopathological characteristics of this collision tumour. Through the presentation of this case, we aim to contribute to the understanding of these rare entities and their management considerations.

Primary unifocal thymic Rosai-Dorfman disease: an extremely rare challenge in diagnostic practice

Rosai-Dorfman disease (RDD) is currently considered a group of neoplastic diseases of unknown etiology, with monoclonal proliferation of histiocytes, showing unique histopathologic features and varying clinical presentation. Primary thymic RDD is an extremely rare extranodal form of this disorder. In this study, we describe the case of an otherwise healthy 64-year-old Chinese man who presented with an isolated, asymptomatic soft tissue density lesion in the anterior mediastinum detected by computed tomography. Histology of the surgical specimen revealed infiltration of thymic tissue by sheets of large histiocytes with mixed lymphocytes and plasma cells, and background fibrosis. Immunohistochemical staining of the histiocytes was positive for S100, CD68, CD163, OCT2 and cyclin D1, but negative for CD1a and BrafV600E expression, thus supporting a diagnosis of RDD. Primary thymic RDD is extremely rare and may be a diagnostic challenge when presenting as mediastinal lesion.

Odontogenic Keratocyst: Unique and Non-Specific Histopathologic Features

Odontogenic Keratocyst: Unique and Non-Specific Histopathologic Features

Anaplastic oligodendroglioma WHO grade 3: Rare brain tumor

The anaplastic oligodendrogliomas are uncommon gliomas. It is clinically significant to know this entity as they have unique clinical, histopathological and molecular features. We present a 43 year female having complaint of headache, tingling numbness, giddiness. Which was of 2 year duration, off and on, and was increased in last 15 days. MRI brain (plain + contrast) showed a large heterogenously enhancing cortical based solid-cystic lesion with surrounding edema in left frontal lobe with mass effects and midline shift. On radiological features impression was suggestive of high grade glial neoplasm and advised biopsy. In our case on histopathology reported as anaplastic oligodendrogliomas WHO CNS grade 3 of left frontal lobe. Patient was treated with surgery, and chemotherapy. We are presenting this rare case of anaplastic oligodendrogliomas for it’s clinical, Histopathological and radiological findings.

Odontogenic-like neoplasms of the rabbit cheek: pathological features and comparison to cutaneous trichoblastoma and jaw-associated ameloblastoma.

Odontogenic neoplasms demonstrate unique histopathological features and are thought to arise from the germinal tissues of the developing tooth germ, effectively restricting their anatomic origin to the tooth-bearing regions of the jaw and directly associated soft tissues of the oral cavity. Ectopic odontogenic-like neoplasms located in the skin of cats, rabbits, and human beings challenge these assumptions. Here we describe the clinical, pathological, and immunohistochemical features of 6 spontaneously occurring odontogenic-like neoplasms arising in the cutaneous tissue of the cheek in client-owned pet rabbits, including ameloblastoma-like (n = 3), ameloblastic fibroma-like (n = 2), and ameloblastic carcinoma-like neoplasms (n = 1). Microscopically, all the cheek tumors featured neoplastic epithelium exhibiting odontogenic architectural structures (plexiform ribbons, anastomosing trabeculae, follicles, cysts, and irregular structures with rounded botryoid protuberances) and 1 or more cardinal odontogenic epithelial features (basal palisading, antibasilar nuclei, and central stellate reticulum-like cells). The pancytokeratin, cytokeratin 5/6, cytokeratin 14, and vimentin immunohistochemical patterns of these odontogenic-like lesions were most similar to those of jaw-associated ameloblastoma and differed from those of cutaneous trichoblastoma. All neoplasms were narrowly excised, and for lesions with clinical follow-up information, none had evidence of recurrence 1-7 months after surgical removal. Although evidence suggests that these odontogenic-like tumors of the rabbit cheek may be derived from ectopic rests of transformed tooth germ, the histogenesis of these lesions remains unresolved.

Basosquamous cell carcinoma: A specific finding of a basaloid squamous cell transition

Basosquamous cell carcinoma is a relatively rare tumor with unique histopathological features of both basal and squamous cell carcinoma. Herein, we report a case of basosquamous cell carcinoma on the face of an elderly male.

Mammary Paget's Disease of Young Females: Case Reports and Comparison With Middle-Aged and Elderly Patients.

Mammary Paget's disease (PD) in young women has seldom been reported. The aim of this study was to improve the knowledge of the clinicopathological characteristics in young patients with PD to provide a basis for the precise treatment of young patients. The medical records and pathological slides of 8 young patients (younger than 40 years old) with PD were reviewed. The data of 20 patients over 40 years old within the same period were used as controls. The average age was 32.00 ± 3.96 years for the young patient group, with the youngest aged 27 years. The first symptom, physical examination, Paget cell morphology, and immunohistochemical marks were the same in different age groups. But young patients have varied tumor distribution patterns, fewer interstitial inflammatory cells, and advanced pathological local lymphatic metastasis than older patients in the same period. PD in young women has unique histopathological features. These manifestations seem to provide personalized treatment for PD treatment in young patients. More research is needed to clarify the significance of this research.

Minocycline-Induced Hyperpigmentation: Importance of Early Diagnosis

A 75-year-old woman on hemodialysis for end-stage renal failure due to polycystic kidney disease developed dark spots on her limbs. She had been treated for extended spectrum beta-lactamase–producing Escherichia coli bacteremia by a rectovaginal fistula and was on long-term oral minocycline (cumulative dose 45 g). Physical examination revealed dark patches on her forearms and lower legs but no trunk hyperpigmentation or visual impairment. Blood tests were normal. Skin biopsy confirmed minocycline-induced hyperpigmentation. Minocycline-induced pigmentation is categorized into types I–IV, each with unique clinical and histopathological features. Types I and II are reversible upon discontinuing minocycline, whereas types III and IV are permanent. The patient was diagnosed with type II pigmentation, generally occurring with a cumulative dose exceeding 70–100 g; however, her lower dose (45 g) led to pigmentation, possibly influenced by her vitamin D deficiency. Clinicians should evaluate the antimicrobial indication and treatment period, considering not only the benefits but also the side effects and antimicrobial resistance. If minocycline is used, attention should be paid to minocycline-induced hyperpigmentation, and this possibility should be communicated to patients to enable early detection.