A Case of Secondary Hemophagocytic Lymphohistiocytosis in a Patient With T-cell Lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that results from excessive immune activation and inflammation. This condition may be triggered by various factors, including infections, malignancies, or autoimmune diseases. Here, we report the case of a 39-year-old male who developed HLH secondary to T-cell lymphoma and had a history of multiple autoimmune disorders. Our patient presented with shortness of breath and weakness which led to an admission for methicillin-resistant Staphylococcus aureus bacteremia. His hospital course deteriorated rapidly due to his worsening condition. He was confirmed to have HLH based on the HLH-2004 criteria with the presence of fever, splenomegaly, hypertriglyceridemia, hypofibrinogenemia, low natural killer cell function, high ferritin, and soluble interleukin 2 receptor levels. Peripheral blood smear and bone marrow biopsy showed atypical lymphocytes consistent with a T-cell lymphoma, but no hemophagocytosis. He was treated with dexamethasone and etoposide. Despite treatment, the patient passed away. This case aims to contribute further to the understanding of secondary HLH in the setting of T-cell lymphoma. It also illuminates how vital early recognition and treatment are in patients with secondary HLH.

High-grade large cell neuroendocrine carcinoma of the esophagus: a case report and review of the literature.

BACKGROUND: Neuroendocrine carcinomas are extremely rare in the esophagus as they represent less than 0.04% of all neuroendocrine tumors. To date, only 14 cases of poorly differentiated, high-grade esophageal NEC have been described in the literature. The majority of these patients presented with typical dysphagia symptoms. Due to its rarity, no standardized guidelines have been proposed to treat esophageal neuroendocrine carcinoma, although general recommendations suggest surgery with adjuvant chemoradiotherapy as the treatment of choice. CASE PRESENTATION: A 67-year-old previously healthy White male presented with a year-long intermittent nonspecific retrosternal discomfort, with the absence of any other symptoms. Esophagogastroduodenoscopy revealed an ulcerative mass in his lower esophagus, with concern of malignancy. Endoscopic ultrasound-guided biopsy revealed poorly differentiated neuroendocrine carcinoma of the esophagus with metastasis to a diaphragmatic lymph node. He was treated with neoadjuvant chemoradiation followed by surgery, and he has been in remission for over 5 years. CONCLUSION: Here, we review the literature and report a unique case of a patient with a vague presentation of esophageal neuroendocrine carcinoma as he enters his sixth year of survival following neoadjuvant chemoradiotherapy.

Severe Hyponatremia During First Cycle of Cyclophosphamide/Doxorubicin Chemotherapy.

Syndrome of inappropriate anti-diuretic hormone release (SIDAH) is a condition characterized by an unregulated release of anti-diuretic hormone (ADH) resulting in increased water retention and decreased plasma osmolarity. Without regulation, ADH release will cause a significant decrease in plasma sodium concentration and can present with cramping, nausea, vomiting, and in severe cases, seizures, and potentially falling into a comatose state. The causes of SIADH are variable and range from infections, some malignancies to some medications. We report a rare case of SIADH resulting from a single cycle of doxorubicin and cyclophosphamide chemotherapy in a 66-year-old female with left and right, estrogen receptor positive breast cancer who experienced seizures resulting from a dramatic drop in sodium levels.

Metaplastic Breast Cancer: Characteristics and Survival Outcomes.

Objectives Metaplastic breast cancer (MBC) is a rare neoplasm accounting for <1% of all breast cancer. We evaluated the clinical characteristics and survival outcomes of MBC. Methods Patients diagnosed with pathologically proven MBC were reviewed from the institutional breast cancer database from 2000 to 2017. Results A total of 136 patients diagnosed with MBC were included in the study. The median age of the diagnosis was 60 years, and 60% of patients were stage II at diagnosis, and 22% were stage III. About two-thirds of the patients were triple-negative; 93% had nuclear grade III, and 25% had a lymphovascular invasion. Squamous differentiation (29%) was the most common histologic subtype, followed by the spindle subtype (21%). The most common distant metastases were lung (22%), followed by bone (13%). Moreover, 60% had a mastectomy, 19% had endocrine therapy, 58% had radiation, 51% received anthracycline-based chemotherapy, 26% had non-anthracycline chemotherapy, and 22% received no chemotherapy. In the entire cohort, the two-year overall survival (OS) and five-year OS were 79% and 69%, respectively, and the two-year progression-free survival (PFS) and five-year PFS were 72% and 61%, respectively. On multivariable analysis, the stage of MBC (stage III: hazard ratio (HR), 5.065 (95% confidence interval (CI), 1.02-25.27) (p=0.048)), poor functional status (Eastern Cooperative Oncology Group (ECOG) score, 2; HR, 24.736 (95% CI, 1.92-318.73) (p=0.014)), and distant metastasis to the brain (HR, 8.453 (95% CI, 1.88-38.04) (p=0.005)) and lung (HR, 42.102 (95% CI, 7.20-246.36) (p<0.001)) were significant predictors of decreased OS. Conclusions MBC demonstrated early disease progression and poor overall survival. The stage of MBC, decreased performance status, and metastasis to the lung and brain were independent poor prognostic factors.

Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes.

Background and Objective: The histologic variants of urothelial carcinoma (UC) are tumors arising from within the urothelium in which some component of the tumor morphology is other than urothelial. They are underdiagnosed, aggressive and have varying pathologic response rates to systemic chemotherapy. There are no consensus guidelines on the use of systemic chemotherapy in variant histology (VH) of UC. We performed a contemporary review on pathologic response rates to neoadjuvant systemic therapy and survival outcomes following radical cystectomy in order to provide a rationale for clinical practice recommendations on the management of UC with VH. Methods: A PubMed literature search was conducted for all English articles from inception reporting either pathological response rates to neoadjuvant treatment or survival outcomes after radical cystectomy in non-metastatic VH of UC. Key Content and Findings: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy was shown to be a beneficial treatment strategy in UC with VH. The micropapillary, plasmacytoid, nested and sarcomatoid histologic variants were associated with worse survival outcomes compared to conventional UC and UC with squamous or glandular differentiation despite initial downstaging with chemotherapy. There is evidence of improved survival in patients with sarcomatoid differentiation receiving NAC compared to RC alone. The major prognostic factors that affect survival outcomes in VH of UC include histologic variant subtype, patient age, presence of lymphovascular invasion, hydronephrosis, nodal metastasis and advanced T stage at diagnosis. Recent studies demonstrate that VH of UC are heterogenous tumors and responsiveness to NAC may be a function of the molecular subtypes present. Conclusions: Based on these findings, NAC to achieve pathologic downstaging prior to radical cystectomy is recommended for MIBC with VH. Biomarkers identified by molecular profiling with immunohistochemistry will need to be validated as predictors of response to NAC in future trials.

Spermatic Cord Liposarcoma: A Case Report and Review of the Literature on the Role of Radiotherapy and Chemotherapy in Preventing Locoregional Recurrence.

Spermatic cord cancer is a rare entity. Among malignant tumors of the spermatic cord, liposarcomas are the most common type, often presenting as painless slow-growing masses usually in the fifth and sixth decades of life; they can be misdiagnosed as inguinal hernia or hydrocele. Radical orchiectomy with wide local soft tissue resection is an accepted standard of care for spermatic cord liposarcoma and has been curative in some cases. There is no definitive role for other treatment modalities such as chemotherapy, retroperitoneal lymph node dissection (RPLND), and radiotherapy. We present a case of liposarcoma of the spermatic cord managed with radical orchiectomy, wide local excision, and was followed up without disease recurrence. We also engage in a review of the literature on the role of systemic chemotherapy and radiotherapy in preventing locoregional recurrence after primary surgery. A combination of surgery and postoperative radiotherapy is effective in preventing locoregional spread. Data from case reports support this strategy in certain histologic subtypes or when margins are positive after primary surgery. A follow-up period of up to a decade after surgery is recommended.

A Rare Case of Emphysematous Gastritis Secondary to Chemotherapy.

Emphysematous gastritis is a rare medical condition characterized by the presence of intra-mural air in the stomach associated with portal venous air tracking to a variable degree. There are no established guidelines favoring surgery over medical management. We present a case of a 64-year-old Caucasian male with a history of stage four colon adenocarcinoma with peritoneal carcinomatosis, malignant ascites, and liver metastasis status post-three cycles of chemotherapy who presented to the emergency room with complaints of generalized abdominal pain, nausea, non-bilious vomiting, and melena stools. He was managed conservatively as a case of sepsis secondary to emphysematous gastritis and made a full recovery. To our knowledge, this is the first reported case of emphysematous gastritis in an adult with colon cancer. Although we cannot establish a causal link between his chemotherapy regimen and emphysematous gastritis, the combined effect of an immunosuppressive state caused by advanced malignancy and cytotoxic effects of chemotherapy are the probable risk factors in our patient. We described the possible mechanisms of mucosal disruption by fluorouracil and bevacizumab in our case. Despite historically having a poor prognosis, emphysematous gastritis can be managed conservatively on a case-by-case basis. Clinicians should be aware that chemotherapy can be a predisposing factor to developing this rare condition.

Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors.

CONTEXT: Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have nonspecific clinical presentations and variable timelines, making their early diagnosis challenging. OBJECTIVE: To identify risk factors, timelines, and prognosis associated with irEEs development. DESIGN AND SETTING: Retrospective observational study within the Cleveland Clinic center. PATIENTS: Metastatic cancer adult patients who received ICIs were included. METHODS: 570 charts were reviewed to obtain information on demographics, ICIs used, endocrine toxicities, cancer response to treatment with ICI, and overall survival. MAIN OUTCOME MEASURES: Incidence of irEEs, time to irEEs development and overall survival of patients who develop irEEs. RESULTS: The final cohort included 551 patients. The median time for the diagnosis of irEEs was 9 weeks. Melanoma was associated with the highest risk for irEEs (31.3%). Ipilimumab appeared to have the highest percentage of irEEs (29.4%), including the highest risk of pituitary insufficiency (11.7%), the most severe (Grade 4 in 60%) and irreversible (100%) forms of irEEs. Forty-five percent of patients with irEEs had adequate cancer response to ICI compared to 28.3% of patients without irEEs (P = 0.002). Patients with irEEs had significantly better survival compared to patients without irEEs (P < 0.001). CONCLUSIONS: In the adult population with metastatic cancer receiving treatment with ICI, irEEs development may predict tumor response to immunotherapy and a favorable prognosis. Ipilimumab use, combination ICI therapy, and melanoma are associated with a higher incidence of irEEs.

Outcomes and management of immune thrombocytopenia secondary to COVID-19: Cleveland clinic experience.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired disease characterized by thrombocytopenia secondary to autoantibodies against platelets. Here, we report the clinical characteristics of coronavirus disease 2019 (COVID-19)-induced ITP cases. STUDY DESIGN AND METHODS: We retrospectively reviewed 3255 COVID-19 patients. COVID-19-induced ITP was diagnosed after excluding possible common causes. Bleeding severity was assessed based on the modified World Health Organization (WHO) bleeding severity score. RESULTS: We identified 11 (0.34%) patients with COVID-19-induced ITP. Of all patients, 63.6% were males and the median age was 63 years. The median time from COVID-19 diagnosis to the onset of ITP was 10 days. Bleeding observed in 63.6% of the patients. Clinically significant bleeding (WHO Grade 3) occurred in single patient who required blood transfusion. Standard treatment with glucocorticoids and intravenous immunoglobulin (IVIG) was effective in achieving excellent response in most cases. Of all patients, complete response and response to treatment were achieved in 45.5% and 27.3% patients, respectively. The median time to ITP recovery was 4 days. Eltrombopag was used in three patients who relapsed. Four patients required mechanical ventilation, and none of them survived secondary to hypoxic respiratory failure. CONCLUSION: ITP secondary to COVID-19 usually presents after the first week of symptoms beginning. Most of our patients had WHO Grade 1-2 bleeding scores. Standard treatment with glucocorticoids and IVIG is effective in achieving an excellent response. The safety of eltrombopag is not very well established in COVID-19 patients, and additional studies are needed for a better safety profile.

Prognostic impact and risk factors of cancer-associated thrombosis events in stage-IV cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Cancer-associated thrombosis (CAT) is a major cause of mortality in cancer patients. Immune checkpoint inhibitors (ICIs) have been associated with multiple side effects including CAT. The aim of this study is to investigate risk factors and prognostic impact associated with CAT events during ICIs treatment. METHODS: This is a multi-center retrospective study that included stage IV cancer patients treated with ICIs. RESULTS: We identified 552 cancer patients treated with ICIs. During follow-up time, 58 (10.5%) patients developed 67 venous thromboembolism (VTE) events while on ICIs. Anticoagulation use at the time of ICIs treatment start was associated with significantly higher VTE incidence rate (IRR: 2.23). No significant difference in VTE IRR was observed depending on response to ICIs treatment, aspirin use, or Khorana VTE risk score. Melanoma as primary cancer, Khorana score, ECOG status, and anemia at baseline were able to predict mortality. CONCLUSIONS: The incidence of CAT in stage-IV cancer patients treated with ICIs was higher in our study compared to previous reports. Control group of patients who did not receive ICIs is needed for better identification of CAT risk factors. Khorana score was a good predictor of mortality but not CAT risk and needs to be further validated in a homogenous group of patients.