Metastatic Clear Cell Carcinoma of Unknown Primary Origin in an Elderly Female Patient With Paraneoplastic Hypercalcemia.

Metastatic clear cell carcinoma (mCCC) is a rare histological subtype of cancer with ovarian and renal origins most common primary sites. Cancer of unknown primary origin (CUP) is a rare type of cancer in the United States and the most common histologic subtypes are adenocarcinoma, squamous cell cancer, and neuroendocrine cancer. We are presenting a rare case of an 86-year-old female patient with mCCC of unknown origin, biopsy and staining showed renal and ovarian in the differential of primary cancer type. However, the patient did not survive the aggressive nature of mCCC and was unable to get any trials of chemotherapy. Primary sites of adenocarcinoma of unknown origin are most common in the breast, lung, pancreas, prostate, colon, and liver. In most cases, empiric chemotherapy with platinum-based agents is the standard of care but needs more data to manage CUP, making it difficult to identify the primary site.

Triple Lymphoma and Transformation to Diffuse Large B-Cell Lymphoma Finding at the Time of Diagnosis.

In this report, we present the case of a patient with an uncommon triple diagnosis of (1) follicular (nodular) lymphoma, (2) nodular lymphocyte predominant Hodgkin lymphoma, and (3) diffuse large B-cell lymphoma non-germinal center B-cell (non-GCB) subtype. Although transformation of follicular lymphoma and nodular lymphocyte predominant lymphoma to more aggressive forms such as diffuse large B-cell lymphoma is possible; it generally happens many years after diagnosis. Moreover, there have been reported cases of follicular lymphoma with transformation and nodular lymphocyte predominant Hodgkin lymphoma with transformation at the time of diagnosis, but it is very uncommon to see all three present on initial diagnosis. Our patient presented with a large right axillary mass, which, upon excisional biopsy and subsequent histology, showed the aforementioned lymphomas. The patient did not present with a prodrome of any symptoms except intermittent night sweats. The unique aspect of our case is that transformation and all three lymphomas were seen at the time of diagnosis. The R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy regimen is still the standard method of treatment as it has been shown to be effective in treating follicular lymphoma and nodular lymphocyte predominant Hodgkin lymphoma with and without transformation. However, there is insufficient literature on its efficacy when all three are present concurrently.

Hairy Cell Leukemia: Hepatic Affinity Status Post Splenectomy.

Hairy cell leukemia (HCL) is a rare neoplasm of the B-cell lineage that is characterized by an indolent course and infiltration of the spleen, the bone marrow, and the reticuloendothelial system. Splenectomy is considered an effective treatment for peripheral cytopenia in patients with HCL. Hepatic involvement of hairy cells with infiltration of the sinusoidal endothelial cells is rarely reported in the literature and is not well understood. We present the case of an 88-year-old male with a history of traumatic splenectomy who was found to have a relapse of classic hairy cell leukemia within the hepatic portal system.

Efficacy and tolerability of isocitrate dehydrogenase inhibitors in patients with acute myeloid leukemia: A systematic review of clinical trials.

BACKGROUND: Acute myeloid leukemia (AML) is a hematological malignancy due to anomalous differentiation and proliferation of hematopoietic stem cells with myeloid blast buildup. Induction chemotherapy is considered the first line of treatment in most patients with AML. However, targeted therapy in the form of FLT-3, IDH, BCL-2, and immune checkpoint inhibitors, can be considered as the first line depending on their molecular profile, resistance to chemotherapy, comorbidities, etc. This review aims to assess the tolerability and efficacy of isocitrate dehydrogenase (IDH) inhibitors in AML. METHODS: We searched Medline, WOS, Embase, and clinicaltrials.gov. PRISMA guidelines were followed in this systematic review. 3327 articles were screened, and 9 clinical trials (N = 1119) were included. RESULTS: In randomized clinical trials (RCTs), objective response (OR) was reported in 63-74% of the patients with IDH inhibitors + azacitidine as compared to 19-36 % of the patients with azacitidine monotherapy in newly diagnosed (ND) medically unfit patients. Survival rates were significantly improved with the use of ivosidenib. OR was reported in 39.1-46 % of the patients who relapsed/refractory to chemotherapy. ≥Grade 3 IDH differentiation syndrome and QT prolongation were reported in 3.9-10 % and 2-10 % of the patients, respectively. CONCLUSION: IDH inhibitors (ivosidenib for IDH-1 and enasidenib for IDH-2) are safe and effective in treating ND medically unfit or relapsed refractory patients with IDH mutation. However, no survival benefit was reported with enasidenib. More randomized multicenter double-blinded clinical studies are needed to confirm these results and compare them with other targeting agents.

A rare case of a peripheral Ewing sarcoma primitive neuroectodermal tumor of pelvic origin.

Primitive neuroectodermal tumors (PNET) represent malignant neuroectodermal tumors composed of small round cells. They can be differentiated between originating from the peripheral nervous system or the central nervous system. Peripheral PNET (pPNET) can be further subclassified as one of the Ewing family tumors (EFT). Although rare, EFT can originate in the female genital tract and pelvic region. Here, we present a case of a middle-aged female with PNET masses in her uterus, abdomen, and hepatic lobes. We discuss the diagnostic modalities, including immunohistochemistry, histopathology, and imaging findings associated with this rare malignancy.

Safety and Efficacy of Tyrosine Kinase Inhibitors in Immune Thrombocytopenic Purpura: A Systematic Review of Clinical Trials.

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.

Carcinoma Erysipeloides: An Underdiagnosed Phenomenon of Cutaneous Metastases of Breast Cancer.

BACKGROUND Cutaneous metastatic breast cancer is a rare manifestation. Causes include vascular or lymphatic spread or iatrogenic mechanisms following surgery. A sub-type of this disease process, "Carcinoma Erysipeloides," represents subcutaneous and dermal tissue layer invasion via lymphatic spread. Diagnosis can be challenging, and therefore, obtaining a thorough history and physical, with careful inspection of prior surgical scars is essential for an accurate diagnosis. Lesions present in variable ways, including papules, plaques, ulcerations, nodules, crusting, or fungating masses, with common locations in the chest, scalp, abdomen, and less commonly the arms. When carcinoma erysipeloides is identified, it is imperative to evaluate for distant metastases. Recent literature has identified benefits with trastuzumab deruxtecan therapy instead of trastuzumab emtansine, with decreased progression rates and decreased mortality rates. Metastasis to the skin can indicate advanced disease; however, this metastatic site may be preferable to visceral organs or bones in terms of prognosis. CASE REPORT We present a rare manifestation of metastatic breast cancer in 45-year-old Hispanic woman, status post neoadjuvant chemotherapy and radical cystectomy on maintenance trastuzumab and pertuzumab. We discuss the clinical presentation variability, keys to diagnosis, treatment considerations, and outcomes for this unique patient population. CONCLUSIONS Carcinoma erysipeloides varies in clinical presentation, especially when patients develop exclusive skin lesions. We identify common etiologies for this progression of disease and discuss combination therapy which has demonstrated a reduction in mortality in this patient population.

BRAF Inhibitors in BRAF-Mutated Colorectal Cancer: A Systematic Review.

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths globally. BRAF mutation is present in about 10% of CRC patients and is associated with a poor response to chemotherapy. These patients have a relatively poor prognosis. This review aims to assess the efficacy and safety of BRAF inhibitors in BRAF-mutated CRC patients. A literature search was performed on PubMed and Embase, and clinical trials relevant to BRAF inhibitors in CRC were included. Data were extracted for efficacy and safety variables. Two randomized clinical trials (n = 765) and eight non-randomized trials (n = 281) were included based on inclusion criteria. In RCTs, an overall response was reported in 23% of the patients treated with BRAF inhibitor-based regimens compared to 2.5% with control regimens. The hazard ratio of overall survival was also significantly better with triplet encorafenib therapy at 0.52 (95% CI = 0.39-0.70). In single-arm trials, ORR was 17% and 34% in two-drug and three-drug regimens, respectively. BRAF inhibitor-based regimens were safe and effective in the treatment of BRAF-mutated CRC. Large-scale randomized trials are needed to find a suitable population for each regimen. PROSPERO registration No. CRD42023471627.

Gynecomastia and Malignancy: A Case of Male Invasive Ductal Breast Carcinoma Treated with Neoadjuvant Chemotherapy.

BACKGROUND Male breast cancer represents a rare malignancy with identifiable risk factors, including genetics, radiation exposure, liver dysfunction, and concomitant diagnosis of Klinefelter syndrome. Gynecomastia can commonly present in these patients, and despite increased estrogen levels in adipose breast tissue, gynecomastia has not been proven to be a significant risk factor for carcinoma development. Male patients with new-onset breast masses are recommended to undergo diagnostic mammograms and breast ultrasound for further evaluation. Those diagnosed with breast cancer most commonly have invasive ductal carcinoma of the breast, and over half of these patients are found to have estrogen and progesterone receptor (ER/PR) positivity. CASE REPORT In this case report, we present a Black man with gynecomastia and an areolar lesion for a 6-month duration following a traumatic event. He was initially referred to the surgical team for further evaluation, and subsequent imaging and biopsy data revealed ER/PR-positive invasive ductal carcinoma. Multidisciplinary discussions were held, and the patient was arranged to begin neoadjuvant treatment with doxorubicin hydrochloride and cyclophosphamide, followed by treatment with paclitaxel (AC-T) chemotherapy, followed by bilateral mastectomy and adjuvant hormonal therapy. CONCLUSIONS The treatment of male breast cancer has remained relatively like that of female breast cancer, which may be due to the limited data in the treatment of male breast cancer. Thus far, studies involving neoadjuvant chemotherapy of female patients have demonstrated promising responses to expand surgical options for patients and possibly decrease the rates of recurrence. Additional studies are warranted to discern optimal therapy for the male patient population.

Chemotherapy Port Induced SVC Thrombosis in a Patient with Non-metastatic Breast Cancer.

Cancer patients are at a higher risk of complications such as venous thromboembolism (VTE). This risk increases in patients who receive chemotherapy. Despite the increased risk, common locations for VTE are similar to those in patients without cancer. Chemotherapy-port-related thrombosis represents a rare complication due to the location and frequent use of access (with Heparin flushes) as part of the standard care. Attention should be made to this rare complication, which may progress to superior vena cava (SVC) syndrome. SVC syndrome typically presents in females around the age of 57 years old. Management of this syndrome can be difficult and generally requires the initiation of systemic anticoagulation therapy. Here, we present a rare case of a 45-year-old female who presented to the Emergency Department with right arm swelling, found to be secondary to her chemo port thrombosis, causing SVC syndrome.

5-Fluorouracil-related Cardiotoxicity with Coronary Vasospasms.

FOLFIRINOX has been commonly utilized to treat patients with pancreatic cancer; however, it can manifest with rare, significant adverse effects. In particular, 5-FU has been associated with cardiotoxic effects, including but not limited to ischemic events, myocarditis, cardiac arrhythmias, cardiac death, heart failure, as well as coronary vasospasm. Two common thought processes regarding the mechanism of cardiotoxicity with 5-FU include exacerbation of ischemia secondary to coronary vasospasm and direct cell injury to the myocardium. Management of cardiotoxic adverse effects includes discontinuing 5-FU therapy if the patient can tolerate an alternative regimen or initiating prophylactic antianginal treatments with very close monitoring of the patient while they receive 5-FU therapy. Here, we describe a case of a 77-year-old patient with stage III pancreatic cancer who developed coronary vasospasm after initiation of combination therapy including 5-FU. Additional studies to gain further understanding of 5-FU cardiotoxicity are warranted, especially considering the common use of this medication with regards to pancreatic cancer patients. Further research of this topic may benefit patient care, prevent cardiovascular events, and determine which patients may benefit from prophylactic therapy while receiving 5-FU.

A Rare Case of Paraneoplastic Syndrome of Inappropriate Secretion of Antidiuretic Hormone in Cervical Squamous Cell Carcinoma; A Case Report and Literature Review.

SIADH is more commonly associated with small cell lung cancer but has also been associated with other malignancies such as oropharyngeal, gastrointestinal, genitourinary, endocrine, lymphomas, and sarcomas. There have been few reports of small cell carcinoma of the cervix complicated by SIADH; however, not many cases are associated with squamous cell carcinoma of the cervix. We present a case of a patient with squamous cell carcinoma of the cervix with a paraneoplastic syndrome of inappropriate secretion of antidiuretic hormone. The pathophysiology, clinical picture, and treatment are also discussed.

A rare case of tophaceous gout manifesting as an osteolytic lesion of the acromioclavicular joint.

An osteolytic lesion on imaging can be considered malignancy until proven otherwise. However, advanced stages of gout have presented with sclerotic rims and lytic lesions thought to be due to overexpression of osteoclasts. Patients have been found to demonstrate osteolytic lesions in patellar regions, which are common locations for gout to manifest; however, to our knowledge, no other cases of osteolytic gout in the acromioclavicular joint have been reported at this time. We report a rare case of a 56-year-old male who presented with acute-on-chronic left upper extremity pain and was found to have an osteolytic lesion of the shoulder on imaging. This lesion was later biopsied and found to be histologically consistent with gout. This case report aims to elucidate further understanding of the various ways that gout can present, to diagnose and treat these patients more effectively.

An Unexpected Transformation: Malignant Spindle Cell Carcinoma Developed From Primary Basal Cell Carcinoma.

Spindle cell carcinoma (SpCC)/sarcomatoid carcinoma is a biphasic tumor with molecular and histopathological properties of both epithelial and mesenchymal tumors. SpCC usually occurs either in sun-exposed areas like the head, neck, upper extremities, and chest or in the areas of skin with prior radiation exposure or in immuno-suppressed individuals. Cutaneous SpCC is a very rare disease, with only a handful of reported cases so far. SpCC differs from conventional squamous cell carcinoma (SCC) with dermal infiltration of atypical keratinocytes as single cells with hyperchromatic eosinophilic cytoplasm and elongated, pleomorphic nuclei with multiple nucleoli, in contrast to cohesive nests or islands in SCC. The objective of this study is to complete a review of the current literature and present a rare manifestation of malignant SpCC which developed from a localized basal cell carcinoma following excision and radiation therapy (RT) in a 79-year-old female. We plan to elucidate the importance of a timely and accurate diagnosis of this disease in order to maximize treatment options and improve survival outcomes.

Pulmonary Carcinosarcoma: A Rare Disease With Challenging Diagnosis and Treatment.

Pulmonary carcinosarcoma (PCS) is a rare type of non-small cell cancer. Overall, middle-aged and older smokers are the most affected age and sex groups. The diagnosis of PCS is difficult due to the absence of characteristic imaging findings. Additionally, preoperative biopsies do not usually reflect the heterologous nature of this tumor. Given the rarity of such tumors and the challenging diagnosis, the prognostic factors have not been established, and the overall prognosis remains poor. The valid therapeutic options are still limited. Here, we report a rare case of metastatic PCS that was accidentally discovered by imaging and properly diagnosed after surgical resection. The clinicopathological features, diagnostic tools, genetic theories, prognosis, and therapeutic options of this rare cancer are also discussed.

Cerebral venous sinus thrombosis in pregnancy presenting with hemiplegia: A case report.

Cerebral venous sinus thrombosis (CVST) is a rather uncommon disorder. CVST is potentially lethal, therefore early detection and treatment is critical. CVST has been linked to pregnancy and puerperium, while COVID-19 infection has been linked to a hypercoagulable state. CVST can be difficult to detect and treat due to the wide range of neurological manifestations, especially in patients with hypercoagulability. The goal of this study is to conduct a literature review and present a unique case of a pregnant woman with CVST who had left hemiplegia and headache. After 6 months of treatment in the hospital, the patient's hemiplegia was fully resolved. Here, we discuss the treatment of CVST in pregnant women who have a suspected past COVID-19 infection.

A rare case of metastatic pancreatic adenocarcinoma presenting as a pulmonary embolism from nonbacterial thrombotic endocarditis.

Nonbacterial thrombotic endocarditis (NBTE) also called, "Marantic endocarditis" occurs due to an underlying hypercoagulable state causing tissue damage and upregulation of the coagulation cascade, with noninfective vegetation formation on heart valves. Mitral and aortic valves are most commonly involved. NBTE is rare, with an incidence of 1.6%, with 65 cases identified during a 10-year autopsy analysis. The most common malignancies associated with NBTE include gynecological cancers, lung cancer, gastric cancer, and pancreatic cancers with adenocarcinoma histology being the greatest risk. Herein, we present a rare case of a 55-year-old male who presented with acute hypoxic respiratory failure secondary to pulmonary embolism due to nonbacterial thrombotic endocarditis. He was found to have advanced pancreatic adenocarcinoma on further investigation of the 2.2 cm hypodense cystic mass in the distal pancreatic body and tail, and complex liver masses which were incidentally found on computed tomography angiography (CTA) of the chest. This is a rare phenomenon and clinicians have to consider the hypercoagulable state associated with cancers, particularly pancreatic adenocarcinoma, and the risk of NBTE.

Recurrent Hypokalemia as an Unusual Presentation for Metastatic Adrenocortical Cancer.

Adrenocortical cancer is a rare malignancy of the endocrine system. Therefore, when this malignancy presents with metastatic disease, this leads to further difficulties in management. Due to the rare and ambiguous nature of this malignancy, diagnosis is generally made at later stages, with limited options for patients. Symptoms may include weight gain/loss, muscle weakness, abdominal discomfort/bloating, hyperglycemia, hypertension, electrolyte imbalance, hirsutism and virilization in females, gynecomastia and hypogonadism in males. Due to the variety of conditions presenting with one or more of these symptoms, diagnosis can be difficult. Many adrenocortical tumors, malignant and benign, are usually detected incidentally on imaging performed for evaluation of another condition, also known as "incidentalomas." Here, we present a rare case of metastatic adrenocortical malignancy in a 56-year-old female patient who presented with isolated recurrent episodes of hypokalemia.

Tetrad of DKA, Hypertriglyceridemia Induced Pancreatitis and Splenic Vein Thrombosis.

Patients with diabetes mellitus have diabetic dyslipidemia that occurs due to disturbances in glucose metabolism and can lead to hypertriglyceridemia (HPTG). Severe HPTG is associated with significantly increased risk of developing acute pancreatitis (AP). Acute pancreatitis (AP) is characterized as an inflammatory condition where inactive digestive enzymes become activated causing pancreatic tissue destruction. Hypertriglyceridemia and the inflammatory state that ensues therein also gives rise to a hypercoagulable state in patients with AP. Splenic vein thrombosis (SVT) is a rare complication of both AP and chronic pancreatitis (CP). We report a Case of 55-year-old Filipino male with past medical history of hypertension and uncontrolled type 2 diabetes mellitus (T2D), who presented with abdominal pain and was found to have diabetic ketoacidosis (DKA), and severe HPTG which led to acute pancreatitis, further complicated by SVT requiring anticoagulation. Our case highlights the importance of strict glycemic control among diabetic patients, the prompt management of AP in the setting of HPTG, and treatment of SVT.