Clear Cell Variant Research Articles

Renal cell carcinoma in a transplanted kidney: a retrospective evaluation

IntroductionKidney transplantation is the optimal treatment modality for patients with end-stage chronic kidney disease. The long-term mortality of kidney recipients is 48–82% lower than that of patients on the waiting list. However, the risk of developing malignancies in these patients is twice as high as in the healthy population. Specifically, the incidence of renal cell carcinoma (RCC) in transplant recipients is 10–30 times higher than in non-transplanted patients. The reason for the increased risk is poorly understood, but is most likely related to continuous immunosuppressive therapy. The problem of kidney graft neoplasia has not been adequately addressed in the medical literature.ObjectiveTo determine the incidence of renal cell carcinoma in transplanted kidneys, enhance the efficacy of its treatment, and study the etiology of RCC development.Materials and methodsA retrospective analysis of RCC incidence in kidney grafts was conducted in 3,270 patients who underwent kidney transplantation between 2013 and 2023. We evaluated the effectiveness of surgical interventions for these complications. Patients with histologically confirmed RCC of the transplanted kidney underwent genetic study to determine the etiology of the neoplasm.ResultsThe incidence of RCC in transplanted kidneys was found to be 0.95% (n = 31), 28 patients underwent laparoscopic resection of the renal transplant tumor, 2 patients were treated with radiofrequency ablation of the tumor. Transplantectomy was performed in 1 patient.ConclusionLaparoscopic resection is an effective and safe method for the treatment of RCC in kidney transplants. Transplanted kidney cancer originates from the donor tissue. The clear cell variant of transplanted kidney cancer is a genetically determined disease.

Long-Term Oncologic Outcomes of Off-Clamp Robotic Partial Nephrectomy for Cystic Renal Tumors: A Propensity Score Matched-Pair Comparison of Cystic versus Pure Clear Cell Carcinoma.

Few data are available on survival outcomes of partial nephrectomy performed for cystic renal tumors. We present the first long-term oncological outcomes of cystic (cystRCC) versus pure clear cell renal cell carcinoma (ccRCC) in a propensity score-matched (PSM) analysis. Our "renal cancer" prospectively maintained database was queried for "cystRCC" or "ccRCC" and "off-clamp robotic partial nephrectomy" (off-C RPN). The two groups were compared for age, gender, tumor size, pT stage, and Fuhrman grade. A 1:3 PSM analysis was applied to reduce covariate imbalance to <10% and two homogeneous populations were generated. Student t- and Chi-square tests were used for continuous and categorical variables, respectively. Ten-year oncological outcomes were compared between the two cohorts using log-rank test. Univariable Cox regression analysis was used to identify predictors of disease progression after RPN. Out of 859 off-C RPNs included, 85 cases were cystRCC and 774 were ccRCC at histologic evaluation. After applying the PSM analysis, two cohorts were selected, including 64 cystRCC and 170 ccRCC. Comparable 10-year cancer-specific survival probability (95.3% versus 100%, p = 0.146) was found between the two cohorts. Conversely, 10-year disease-free survival probability (DFS) was less favorable for pure ccRCC than cystRCC (66.69% versus 90.1%, p = 0.035). At univariable regression analysis, ccRCC histology was the only independent predictor of DFS probability (HR 2.96 95% CI 1.03-8.47, p = 0.044). At the 10-year evaluation, cystRCC showed favorable oncological outcomes after off-C RPN. Pure clear cell variant histology displayed a higher rate of disease recurrence than cystic lesions.

Enigma of Acantholytic and Clear Cell Changes in Oral Squamous Cell Carcinoma.

Only limited cases have been reported about the clear cell variant of squamous cell carcinoma occurring in the oral cavity. The present study regards the case showing the histopathological features of both the clear cell and acantholytic variants of oral squamous cell carcinoma. A review of the literature has been done to understand the pathogenesis of those changes. Also, a hypothesis has been given that the clear cell changes could be the consequences of the cascades of the acantholytic process and not a separate entity. Therefore, more research is required to confirm this hypothesis and understand the prognosis of the lesion.

Recent Advances in The Diagnosis of Well-Differentiated Colon Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are rare tumors that appear with secondary symptoms based on the release of vasoactive peptides and hormones into the blood as an answer to a signal from the nervous system. Neuroendocrine neoplasms of the colon are epithelial neoplasms with neuroendocrine differentiation and are classified in step with the foremost recent WHO 2022 classification as well- differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinoma- mas (NECs. NETs can be divided into serotonin-producing enterochromaffin-cell neuroendocrine tumor and glicentin-PYY-producing L-cell neuroendocrine tumor. Compared to NECs, NETs are often idle lesions occurring as incidental findings, being generally characterized by indolent course and relatively frequent ab- since of specific symptoms, which underscores the significance of establishing a prompt and accurate diagnosis, colonic neuroendocrine tumors generally presenting as a large tumor with local or distant metastasis (generally liver) at the time of diagnosis. While utmost colon NETs are considered non-aggressive tumors, a few cases may show a more aggressive clinical course. Clinical/pathological characteristics to select cases at high threat of recurrence/metastases are sadly inadequately consolidated. Diagnosis is based on the combination of clinical presentation, biochemical markers, endoscopy, imaging and confirmed by histopathology. Differential diagnostic for NETs can cause various problems: the rare appendiceal tubular and clear cell variants (which may be confused with non-neuroendocrine cancers). This review presents the updates in established diagnostic tests and tests that require further development, investigation, and validation before use [1,7].

Case Report] Clear Cell Carcinoma of the Ovary with Disseminated Intravascular Coagulation and Haemoperitoneum with Tumour Rupture

We report a 34-year-old woman with haemoperitoneum and acute disseminated intravascular coagulation (DIC) following rupture of ovarian clear cell carcinoma (OCCC), the first documented case. Although DIC is known to be associated with ovarian cancer, acute DIC with bleeding in clear cell variants is not reported. A patient with a right adnexal lesion was found to have anaemia with thrombocytopenia. Intra-abdominal bleeding with the rupture of a malignant ovarian cyst associated with DIC was found to be the cause. After surgery, DIC resolved, indicating OCCC can be the aetiology for acute DIC and bleeding. Practitioners must know this rare but potentially fatal association between OCCC and acute DIC.

Case Report] Clear Cell Carcinoma of the Ovary with Disseminated Intravascular Coagulation and Haemoperitoneum with Tumour Perforation

We report a case of a 34-year-old woman with haemoperitoneum and acute disseminated intravascular coagulation (DIC) following the rupture of ovarian clear cell carcinoma (OCCC), the first documented case of its kind. Although DIC is known to be associated with ovarian cancer, acute DIC with bleeding in the clear cell variant has not been reported. The patient, who had a right adnexal lesion, was found to have anaemia and thrombocytopenia. Intra-abdominal bleeding due to the rupture of a malignant ovarian cyst associated with DIC was identified as the cause. After surgery, the DIC resolved, suggesting that OCCC can be an aetiology for acute DIC and bleeding.

Management of Cutaneous Squamous Cell Carcinoma (Clear Cell Variant) in Bovine - A Case Report

Tumors of the bovine gastrointestinal tract are rare, possibly because of the low age of the sample population (Bertone, 1990). Neoplasia in cattle carries a poor prognosis because of early adenocarcinoma metastasis and the high fatality of lymphosarcoma. Squamous cell carcinoma is the second most rude type of skin cancer, with basal cell carcinoma being the most common (Rinker et al., 2001). Squamous cell carcinoma has been documented in bovine (Musser et al., 1993). Clear-cell squamous cell carcinoma is a rare variant of squamous cell carcinoma, first described by Kuo (1980) as a skin tumor. The exact etiology is unclear, but ultraviolet radiation has been suggested as a possible cause in humans (Lawal et al., 2013). This report documents a case of cutaneous squamous cell carcinoma (clear cell variant) in perianal region of a cow and its successful surgical management.

Immunohistochemical characterization of clear cell variant of hepatocellular carcinoma in a sheep

The cadaver and viscera of a mature female sheep (Ovis aries) underwent routine abattoir meat inspection. The liver was expanded by an infiltrative neoplastic mass comprising multifocal to coalescing, well-demarcated, pink to white–yellow nodules, up to 25 mm in diameter. An unencapsulated, moderately densely cellular, infiltrative neoplasm was present within the hepatic parenchyma. The neoplastic cells were arranged in solid sheets and acini supported by a moderately fine collagenous vascularized stroma. The neoplastic cells were moderately sized and polygonal, with clearly delineated cell borders and a moderate amount of cytoplasm that was clear or exhibited either globular eosinophilic deposits or fine fibrillar eosinophilic strands. The neoplastic cell nuclei were round and centrally located. The chromatin was lightly stippled and there was frequently a single, prominent, basophilic nucleolus. There were eight mitoses in 10 high-power fields (2.37 mm2). Most of the neoplastic cells had intense cytoplasmic immunolabelling for arginase 1, with frequent concurrent nuclear positivity, and mild to moderately intense punctate cytoplasmic labelling for hepatocyte specific antigen (Hep Par-1). The neoplastic cells did not label with anti-cytokeratin 19 antibody. Based on the histological appearance and the immunolabelling pattern, the neoplasm was diagnosed as the clear cell variant of a hepatocellular carcinoma.

Histological pattern of nephrectomy specimens: A fifteen-year review

Background: Nephrectomy is the surgical removal of all or part of a diseased kidney in a living person. Pathological assessment of the tissue specimen is required in most cases for eventual diagnosis and disease prognostication. Objective: To demonstrate the pathological patterns of nephrectomy specimens in Nnewi, South East Nigeria. Methods: The data of all the nephrectomy specimens submitted to the Department of Histopathology of the Nnamdi Azikiwe University Teaching Hospital, Nnewi, as well as Triple Green Diagnostic Clinics Ltd, Nnewi, from 2007 to 2021 were retrospectively reviewed. Their pathological features were analyzed. Results: Of the 153 nephrectomy specimens, 141 that had complete data were used for the study. Those that had neoplastic lesions were 84(59.6%), while 57(40.4%) were non-neoplastic. Of the neoplastic lesions, 79 (94%) were malignant and renal cell carcinoma (RCC) accounted for 60%, with a mean age of 48.8±18.1 years and median age 52.5 years. RCC occurred commonly in the sixth decade of life (26%) with male preponderance (56%) and predominantly involving the left kidney (64%). Clear cell variant of renal cell carcinoma was the most common (52%), followed by papillary variant (34%). Nephroblastoma was the most common malignancy in the first decade with a modal age of 2years. Chronic pyelonephritis was the most common non-neoplastic lesions. Conclusion: Nephrectomy is done for a wide range of renal pathology, with more done for neoplastic conditions than non-neoplastic ones.

Clear-Cell Mesothelioma of Uterine Corpus: Diagnostic Challenges in Intraoperative Frozen Sections

The clear-cell variant of epithelioid mesothelioma is an extremely rare neoplasm of the peritoneum. It shares histomorphologic features overlapping with a wide variety of tumors including carcinomas and other non-epithelial neoplasms. The diagnosis of peritoneal clear-cell mesothelioma is not always straightforward, despite known immunohistochemistry (IHC) markers. Due to its rarity, this entity may be diagnostically confused with other clear-cell neoplasms, particularly in intraoperative frozen sections. Here, we present a case of clear-cell mesothelioma originating in the uterine serosa that was initially misdiagnosed as clear-cell adenocarcinoma in the intraoperative frozen section. Microscopically, the tumor showed diffuse tubulocystic spaces of variable size lined by clear cells with moderate nuclear atypia. Immunohistochemical staining confirmed the diagnosis of clear-cell mesothelioma. Recognition of this entity, albeit rare, is important as the diagnosis may significantly affect the management considerations. The judicious use of an IHC panel helps to distinguish this tumor from other mimickers.

Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance.

The clear cell variant of renal cell carcinoma (ccRCC) is the most common renal epithelial malignancy and responsible for most of the deaths from kidney cancer. Patients carrying inactivating mutations in the Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several types of tumors including ccRCC. Normally, the Hypoxia Inducible Factor alpha (HIF-α) subunits of the HIF heterodimeric transcription factor complex are regulated by oxygen-dependent prolyl-hydroxylation, VHL-mediated ubiquitination and proteasomal degradation. Loss of pVHL function results in elevated levels of HIF-α due to increased stability, leading to RCC progression. While HIF-1α acts as a tumor suppressor, HIF-2α promotes oncogenic potential by driving tumor progression and metastasis through activation of hypoxia-sensitive signaling pathways and overexpression of HIF-2α target genes. One strategy to suppress ccRCC aggressiveness is directed at inhibition of HIF-2α and the associated molecular pathways leading to cell proliferation, angiogenesis, and metastasis. Indeed, clinical and pre-clinical data demonstrated the effectiveness of HIF-2α targeted therapy in attenuating ccRCC progression. This review focuses on the signaling pathways and the involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer oncogenic potential downstream of the VHL-HIF-2α signaling axis in ccRCC. Discussed as well are current treatment options (including receptor tyrosine kinase inhibitors such as sunitinib), the medical challenges (high prevalence of metastasis at the time of diagnosis, refractory nature of advanced disease to current treatment options), scientific challenges and future directions.

Clear-cell Variant of Mucoepidermoid Carcinoma Presenting as a Palatal Mass in a 10-Year-old Boy.

The clear-cell variant of mucoepidermoid carcinoma (MEC) involving minor salivary glands is extremely rare in children. We report a case of clear-cell variant MEC in the minor salivary gland in a 10-year-old boy who presented with a mass of the right hard palate. Fine-needle aspiration showed features suggestive of clear-cell variant of MEC. Microscopically, the tumor cells showed predominant clear cells and scattered mucous cells. There was increased mitotic activity (6/mm2). No tumor necrosis or nuclear pleomorphism was identified. The tumor cells were positive for cytokeratin 7 (CK7), tumor protein p63, P40 (ΔNp63), CK5/6 and mucicarmine. Rearrangement of mastermind-like transcriptional coactivator 2 (MAML2) (11q21) gene was present in the tumor cells by fluorescence in situ hybridization, supporting the diagnosis of an intermediate-grade clear-cell variant of MEC. A right infrastructure maxillectomy for palate carcinoma with negative margins was performed. Grossly, the tumor was a 2.1 cm well-circumscribed, friable, pale tan mass with focal areas of cystic change. The final pathological diagnosis was clear-cell variant of MEC, intermediate grade, pT2. Post surgery, the patient recovered and was doing well, with no tumor recurrence or metastasis at the 6-month follow-up. To the best of our knowledge, this is the first documented case of clear-cell variant MEC in a child. Due to low to intermediate tumor grade, an overtly aggressive treatment should be avoided in a child.

Метастаз светлоклеточного варианта почечно-клеточного рака в корне языка

This article presents a rare clinical case of metastasis of a clear cell variant of renal cell carcinoma in the root of the tongue 4 years after right-sided nephrectomy. The patient underwent supporting laryngoscope surgery with a CO2-laser (removal of the formation of the root of the tongue) with a preliminary imposition of a tracheostomy, without complications. According to the results of the morphological study, the structures of a clear cell malignant tumor were revealed.

Chromophobe renal cell carcinoma with rare distant metastasis

Metastasis accounts for the most common tumor of the central nervous system (CNS) in adults. Renal cell carcinoma (RCC) is one of the common carcinoma showing brain metastasis, with a predilection for clear cell variant. Chromophobe RCC (ChRCC) in contrast to clear cell RCC shows far less common distant metastasis. When they metastasize, commonly involve the liver, lungs, and lymph nodes. ChRCC metastasizing to the brain is extremely rare. Isolated brain metastasis from RCCs is also uncommon. We report an unusual case of a 54-year-old woman with ChRCC with isolated metastasis to the brain, 2 years after radical nephrectomy for renal mass.

CLEAR CELL VARIANT OF SQUAMOUS CELL CARCINOMA PENIS – A CASE REPORT

Carcinoma penis is a rare malignancy in males. The World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs classifies squamous cell carcinoma of the penis into human papillomavirus (HPV) and non HPV related. Among the HPV-related Squamous cell carcinomas of the penis, clear cell variant is a rare. Here we report a case of clear cell variant of squamous cell carcinoma of penis with bilateral inguinal lymph node metastasis. We have treated this patient with radical surgery, wide excision and bilateral inguinal lymph node dissection followed by post operative chemo radiation. But during radiation itself the disease progressed, with rapid recurrence of inguinal lymph node metastasis, finally end up with palliative chemotherapy. Clear cell carcinoma is an aggressive form of cancer, with frequent metastasis to the inguinal lymph nodes, as seen in this case. Immunohistochemistry examination P16 was absent. So it is considered as clear cell variant of squamous cell carcinoma. Clinical experience with penile carcinoma is limited because of their rarity.

Incidental Diagnosis and Treatment of Renal Cell Carcinoma in a Kidney Pre-Transplant Recipient

Introduction:Renal cell carcinoma (RCC) accounts for 80–90% of all kidney cancers with peak age incidence between 60–70 years. The three commonest symptoms are haematuria, flank pain and flank mass. The best treatment option for chronic kidney disease is renal transplantation. Chronic kidney disease is one of the risk factors for RCC. Most cases are diagnosed after renal transplantation; diagnosis during work up for renal transplantation in an asymptomatic patient is rare, especially in environment where patients hardly receive cure for kidney cancer because most cases are diagnosed late, at the advanced stage of the disease. Case Presentation: A 62-year-old male on management for chronic kidney disease who was diagnosed with right renal tumour during work up for renal transplantation. He had right radical nephrectomy with histology report revealing localized RCC (clear cell variant). He is currently on observation for 2 years before transplantation. Conclusion: Diagnosis of RCC in an asymptomatic patient during work up for renal transplantation is rare. The prognosis of this disease is improved significantly if diagnosed and treated before renal transplantation.

Papillary Renal Cell Carcinoma with Massive Hemorrhage: An Autopsy Case Report

Abstract Introduction/Objective Spontaneous renal hemorrhage is a rare complication of various kidney pathologies. It can be due to renal artery aneurysms, arteriovenous malformations, cystic renal diseases, renal calculus, coagulation disorders, as well as neoplastic lesions like angiomyolipoma and renal cell carcinoma (RCC). Individuals present with sudden flank or scapular pain, hypovolemic shock, termed as Wunderlich syndrome (WS). 30-35% cases of WS are from spontaneously ruptured RCC, commonly clear cell variant (70%) followed by papillary (10-15%) and chromophobe variant (4-6%). We present an autopsy case of a papillary variant RCC identified as a small kidney mass with a pathogenetic correlation behind the intractable bleeding. Methods/Case Report An 81-year-old Caucasian man with a history of atrial fibrillation, on long-term Xarelto treatment, was found to have a 1.2 cm incidental mass in the right kidney. He started experiencing right-sided scapular pain, then rapidly became hypotensive, drowsy. CT scan revealed a large right-sided perinephric and retroperitoneal hematoma (17.5 x 5.7 x 8.9 cm) extending in the pelvis. Despite receiving blood products, other supportive treatment, and successful angio-embolization, his condition worsened to acute kidney injury, bowel ischemia, and persistent lactic acidosis leading to death. On autopsy, bloody ascites, clots on mesenteric root insertion, and bulging in retroperitoneal spaces were seen. The perinephric spaces had organized clots. The bleeding originated from a 2.0 x 2.0 cm brown mass in the middle pole of the right kidney. There was a slit-like vessel at the interface of the kidney and the mass. Microscopic examination of the mass shows trabecula of abnormal cells with abundant eosinophilic cytoplasm in the hemorrhagic and necrotic background. These cells are positive for PAX8, CK7, CD10, dim positive for CAIX, and negative for CD117, which is consistent with renal cell carcinoma, papillary variant. Results (if a Case Study enter NA) NA. Conclusion Papillary RCC is much less vascular and less aggressive than clear cell RCC. However, necrosis or bleeding into renal vessels may occur. In this case, blood-leaks and accumulation in enclosed space followed by necrosis, fibrosis, and hyalinization cause neovascularization forming a negative spiral for re-bleeding. Anticoagulants can lead to profuse sustained bleeding from even very small size RCC.

Clear Cell Variant of Squamous Cell Carcinoma of Skin: A Case Report and Review of the Literature

Clear cell squamous cell carcinoma (SCC) is a rare variant of SCC of skin in which ultraviolet radiation has been suggested as possible etiology. We report a case of a 51-year-old male patient who presented with a 4 months history of a non-healing ulcer on the left side of his face. Histopathology and immunohistochemistry studies showed Clear cell variant of squamous cell carcinoma. This case showed an aggressive and bizarre clinical presentation but more report of cases are needed to have a better characterization of the clinical presentation and prognosis of this variant of this squamous cell carcinoma variant.

Editor’s Letter

Gallbladder carcinomas (GBCs) are the most common carcinomas of the biliary tract. The clear cell variant is encountered rarely, accounting for approximately 1% of all GBCs.Due to its rarity, the exact incidence and pathogenesis of this variant are unknown. Though hyalinising cholecystitis (porcelain gallbladder) is an established risk factor for development of conventional adenocarcinomas of the gallbladder, its role in the pathogenesis of the rare variants of GBC is not well-established. The current case raises the possibility that clear cell carcinoma of the gallbladder may arise through the same pathways as conventional adenocarcinomas of the gallbladder.

Clear Cell Syringoma of the Eyelids, a Distinctive Histopathologic Variant Associated with Diabetes Mellitus.

The authors describe the clinical and histologic findings of the clear cell variant of syringoma. Three adult female patients (age range 39-76 years old) were found to have multiple, flesh-colored lower eyelid papules, clinically consistent with syringomas, but histologically displaying abundant clear cell change. Two patients had known diagnoses of uncontrolled diabetes.