Association between Prostate Carcinoma and Multiple Myeloma.

Synchronous or sequential development of multiple myeloma and prostate carcinoma is rare. It is not sure whether these two occur independently or if one influences the development of the other. We reviewed the cases published in the English literature; eight cases of myeloma developing after diagnosis and treatment for prostate carcinoma, five cases of simultaneous occurrence of myeloma and prostate carcinoma, and five cases where the patient with multiple myeloma later developed prostate carcinoma were found. This short review attempts to analyze the occurrence of these two diseases in the same patient and dissect whether there is a close association or it is just a mere coincidence.

Chemotherapy and Immune Checkpoint Inhibitors in a Case of SMARCA4-dUT: A Case Report and Review of Literature.

SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) are infrequently occurring aggressive neoplasms found predominantly in young male smokers. These tumors are distinguished by the loss of expression of Brahma-related gene 1 (BRG1) due to a deactivating mutation of SMARCA4. Immunophenotype can be variable but characteristically lack the expression of BRG1. SMARCA4-dUT has a poor prognosis and generally progresses or recurs. The median survival is around 6 months. Here, we report a case of a 36-year-old male smoker who presents with multiple right-sided lung masses. The patient was found to have a loss of SMARAC4 and SMARCA2 along with the absence of markers of vascular, melanocytic, lymphoid, keratin, or myogenic origin. Tumor size was reduced significantly after 3 cycles of carboplatin and 1 cycle of pembrolizumab. From reviewing the literature and the clinical course in our case, we suggest combination chemotherapy plus immune checkpoint inhibitor (ICI) therapy to be the first choice of therapy for treating SMARCA4-dUT of lungs. Further research and studies are needed to evaluate the response to ICI therapy alone or combination therapy (chemotherapy plus ICI).

Recurrence of T-Cell Prolymphocytic Leukemia With a Rare Presentation as Diffuse Generalized Skin Lesion.

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm that originates from mature post-thymic T-cells. Cutaneous manifestations are a common presentation in T-PLL but rarely are a presentation in the recurrent setting. Here, we describe the case of a 75-year-old female with a history of T-PLL-who at the time of initial diagnosis did not exhibit any rash-presenting with diffuse rash, facial swelling, sore throat, and dysphagia 7 months later and was found to have recurrent T-PLL. She had diffuse lymphadenopathy and diffuse skin lesions. Biopsy of the skin lesions also confirmed infiltration with T-PLL cells. After review of the literature, no previously reported cases of recurrent T-PLL presented as diffuse skin lesions. This case demonstrates that recurrent T-PLL may present with diffuse rash, respiratory distress, and anasarca. It is important to stay vigilant in patients with history of T-PLL to recognize signs of recurrent disease to allow prompt diagnosis and treatment.

Axillary Lymphadenopathy as an Initial Presentation of Systemic Amyloidosis: A Case Report and Literature Review.

Amyloidosis rarely presents as localized lymphadenopathy. Various studies have elucidated the varied presentation and manifestations of this interesting disease. We reviewed the literature and found 36 cases of primary amyloidosis with lymph node enlargement as a presentation, and 17 of the 36 cases (47%) had systemic involvement on further work up. We describe a patient who presented with an isolated right axillary mass. Clinical examination and radiology were indicative of a lymph node enlargement with no evidence of malignancy in the breasts or lungs. Histopathological examination was indicative of amyloidosis. A further work up including serum, urine biochemistry, cardiac work up, bone marrow examination, and a kidney biopsy revealed systemic amyloidosis. Patient was treated with daratumumab and CyBorD (cyclophosphamide, bortezomib, and dexamethasone) followed by a stem cell transplantation. Patient is in remission for 1 year, at the time of submission of this report. Therefore, we conclude (1) systemic amyloidosis presenting as an isolated lymph node enlargement is rare, (2) a structured systemic work up is imperative for early diagnosis and proper management of amyloidosis, when there is an index of suspicion, and (3) use of novel therapeutic options such as CD38 + antibody (daratumumab) and stem cell transplant have positive impact on disease outcomes.

Hemorrhagic Brain Metastasis as an Initial Presentation of Hepatocellular Carcinoma in a Patient With Alcohol-Related Liver Cirrhosis: A Case Report and Review of Literature.

Hepatocellular carcinoma (HCC) is the most common primary hepatic cancer. Although it usually presents as a liver mass, rarely HCC can have an initial presentation at an extrahepatic site before the diagnosis of the primary lesion in the liver. Even rarely was that brain metastasis as initial extrahepatic presentations. Furthermore, the initial presentation of HCC as brain metastases has been with most cases being secondary to hepatitis-related hepatoma. In this case report, we are presenting a rare and unusual case of hemorrhagic cerebral metastasis as an initial extrahepatic presentation of an alcohol-related hepatoma. Our case is the second case in the English literature that has been presented in such a way. Due to the uncommonness of presentation, there can be diagnostic dilemmas and delay in treatment. Therefore, a high level of suspicion is needed in the high-risk patients of HCC who present with unexplained or new neurological signs and symptoms. More exploration is warranted for clinical research and treatment guidelines for brain metastases of HCC to help improve survival and quality of life.

Review of Checkpoint Inhibitor Immunotherapy in Neuroendocrine Tumor of Prostate and Our Experience in 2 Cases.

Neuroendocrine prostate cancer (NEPC) is a rare entity. De novo NEPC is extremely rare; other cases are usually adenocarcinoma previously treated with hormonal therapies transforming to NEPC. Most of the cases are metastatic at diagnosis and regardless of the histology types, the prognosis is poor. In this report, we reviewed the checkpoint inhibitor (CPI) immunotherapies used for neuroendocrine tumors of the prostate. Very limited data with only a few cases were published which showed a limited activity by immunotherapy; therefore, we present our experience of 2 cases: (1) adenocarcinoma with foci of NEPC and (2) adenocarcinoma transforming to NEPC after treatment with androgen deprivation therapy (ADT); both of which were initially managed with ADT, chemotherapy followed by immunotherapy with durvalumab, a programmed death ligand 1 inhibitor. In these 2 cases, CPI therapy showed limited efficacy, suggesting that neuroendocrine histology is not very responsive to CPI treatment, regardless if onset is early or late. Other therapies need to be explored for the treatment of NEPC.

SMARCA4-Deficient Undifferentiated Tumor of Lung Mass-A Rare Tumor With the Rarer Occurrence of Brain Metastasis: A Case Report and Review of the Literature.

Among thoracic tumors, these include subsets of a relatively newly described and yet to be fully characterized tumor entity: SMARCA4-deficient Undifferentiated Tumor (SMARCA4-dUT). Mutations of SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and loss of BRG1 (Brahma-related gene-1) is the underlying molecular hallmark of SMARCA4-dUT. They mostly involved the mediastinum, lung, and/or pleura showing undifferentiated round cell or rhabdoid morphology associated with aggressive clinical behavior. The pathogenesis of these tumors is still not clear. Morphologically, SMARAC4-dUT is differentiated from SMARCA4-dNSCLC by the presence of squamous and solid components in the latter. Immunohistochemically SMARC4-dUT has characteristic loss of SMARCA4 and SMARCA2 and strong expression of SOX2, CD34, and SALL4. Common sites of metastasis include lymph nodes, bones, and adrenal glands but rarely brain metastasis. We present a unique and rare case of a 76-year-old male with a right lung mass with documented pathology of SMARCA4-dUT and was found to have multiple brain metastases.

Plasmablastic Lymphoma Presenting as Extensive Peritoneal and Retroperitoneal Nodules in an HIV-Positive Patient.

Plasmablastic lymphoma (PBL) is a rare but aggressive subtype of diffuse large B-cell lymphoma (DLBCL). The diagnosis of PBL is challenging as its features overlap with lymphoma and myeloma. The most common presentation involves the oral cavity/jaw in human immunodeficiency virus (HIV)-positive patients. It has also been reported in the gastrointestinal (GI) tract, lymph nodes, and soft tissues. Usually, if PBL involves the GI tract, it presents as a gut tumor mass. In this report, we present an HIV-positive patient with PBL presenting with multiple peritoneal nodules. To our knowledge, this is the first case of PBL presenting as multiple peritoneal and retroperitoneal nodules in an HIV-positive patient. This case emphasizes the rare presentation of a rare malignancy, difficulties in establishing a diagnosis, and the importance of proper and timely management.

COVID-19 in Cancer Patients From New York City: A Comparative Single Center Retrospective Analysis.

In this retrospective study we analyze and compare clinical characteristics and outcomes of patients with and without cancer history who were infected with novel coronavirus disease 19 (COVID-19). Medical records were reviewed and a comparative analysis of 53 cancer and 135 non-cancer patients with COVID-19 were summarized. Results: The median age for COVID-19 patients with and without cancer was 71.5 and 61.6 years, respectively. Patients aged 60 years and above were 86.8% and 60.7% in cancer and non-cancer groups, respectively. A high proportion of cases were seen in African Americans 73.6% (with cancer) and 75.6% (without cancer) followed by Hispanic patients. Male and female patients had a high percentage of prostate (39.3%) and breast (32%) cancer respectively. Prostate cancer (18.9%) and myeloma (11.3%) were common among solid and hematological cancers respectively. Hypertension and smoking were prevalent among cancer (83% and 41.5%) compared to non-cancer (67.4% and 9.6%) patients. The common symptoms in cancer patients were dyspnea (64.2%) followed by fever and cough (50.9%) compared to fever (68.1%) and cough (66.7%) in non-cancer patients. Cancer patients had higher levels of lactic acidosis, C-reactive protein, lactate dehydrogenase, and alkaline phosphatase than non-cancer patients (p < 0.05). Conclusions: Rapid clinical deterioration was seen in cancer patients who were aged 60 years and above. Higher mortality was seen in this subgroup, especially when they had associated hypertension and elevated levels of CRP and LDH.

De Novo CD5+ Primary Gastrointestinal Diffuse Large B-Cell Lymphoma: Challenges With Treatment and Clinical Course.

The gastrointestinal tract is a common extranodal site for lymphomas. However, primary gastrointestinal lymphomas are rare. Diffuse large B-cell lymphomas (DLBCL) are the most commonly encountered type in the gastrointestinal tract. Most of the DLBCL are CD5 negative. CD5+ DLBCL is very rare and a poor prognostic subtype of lymphoma. We report a rare case of primary small bowel CD5+ DLBCL that evolved from being a localized low International Prognostic Index-scored disease into an advanced and aggressive disease primarily dictated by the presence of CD5 antigen positivity.

Psychosocial moderation of polygenic risk for cannabis involvement: the role of trauma exposure and frequency of religious service attendance.

Cannabis use and disorders (CUD) are influenced by multiple genetic variants of small effect and by the psychosocial environment. However, this information has not been effectively incorporated into studies of gene-environment interaction (GxE). Polygenic risk scores (PRS) that aggregate the effects of genetic variants can aid in identifying the links between genetic risk and psychosocial factors. Using data from the Pasman et al. GWAS of cannabis use (meta-analysis of data from the International Cannabis Consortium and UK Biobank), we constructed PRS in the Collaborative Study on the Genetics of Alcoholism (COGA) participants of European (N: 7591) and African (N: 3359) ancestry. The primary analyses included only individuals of European ancestry, reflecting the ancestral composition of the discovery GWAS from which the PRS was derived. Secondary analyses included the African ancestry sample. Associations of PRS with cannabis use and DSM-5 CUD symptom count (CUDsx) and interactions with trauma exposure and frequency of religious service attendance were examined. Models were adjusted for sex, birth cohort, genotype array, and ancestry. Robustness models were adjusted for cross-term interactions. Higher PRS were associated with a greater likelihood of cannabis use and with CUDsx among participants of European ancestry (p < 0.05 and p < 0.1 thresholds, respectively). PRS only influenced cannabis use among those exposed to trauma (R2: 0.011 among the trauma exposed vs. R2: 0.002 in unexposed). PRS less consistently influenced cannabis use among those who attend religious services less frequently; PRS × religious service attendance effects were attenuated when cross-term interactions with ancestry and sex were included in the model. Polygenic liability to cannabis use was related to cannabis use and, less robustly, progression to symptoms of CUD. This study provides the first evidence of PRS × trauma for cannabis use and demonstrates that ignoring important aspects of the psychosocial environment may mask genetic influences on polygenic traits.

Quantification of IGF-1 receptor is useful in the differential diagnosis of essential thrombocytosis from reactive thrombocytosis.

BACKGROUND: To make a definite diagnosis of essential thrombocytosis (ET) from reactive thrombocytosis (RT), the most reliable criteria are the presence of driver mutations, namely JAK2, CALR, or MPL gene mutations. In the absence of these driver mutations, so-called triple-negative ET, the differential diagnosis could be difficult. Although bone marrow biopsy could be helpful, it may be difficult in some cases, to do gene sequence analysis to identify other clonal marker gene mutations than the driver mutations, as only very few were found. METHODS: IGF-1R quantification by flow cytometry in mononuclear cells (MNC) from peripheral blood was performed in 33 patients with ET (untreated or off treatment with hydroxyurea), 28 patients with RT, and 16 normal volunteer controls. RESULTS: We found IGF-1R levels were significantly elevated in ET patients compared to RT patients or controls. A cutoff value of 253 was chosen from the logistic regression to predict each patient's group, a value ≥253 meant that a patient belonged to the ET group (sensitivity 96.4% and specificity 68.6%). CONCLUSION: We suggest that adding quantification of IGF-1R in blood MNC by flow cytometry is useful in differentiating ET from RT.

Hepatocellular carcinoma presenting as spinal cord compression in Native Americans with controlled hepatitis C: two case reports.

BACKGROUND: Hepatocellular carcinoma is a common malignancy in Asia. It is associated with chronic hepatitis B virus or hepatitis C virus infection and alcoholic hepatitis. Commonly, the tumor metastasizes to the lungs, regional lymph nodes, and bone. Recently, the incidence of metastatic spinal cord compression caused by primary hepatocellular carcinoma has been reported more frequently due to improved diagnosis and therapeutic modalities. The presentation of primary hepatocellular carcinoma with spinal cord compression is very rare. To the best of our knowledge, there are only 33 such cases published to date. The majority of cases involve patients of Asian origin and are associated with hepatitis B infection. CASE PRESENTATION: We report consecutive cases of two Native American (American Indian) patients (a 64-year-old man and a 70-year-old man) who presented with symptoms of spinal cord compression due to metastatic spread of hepatocellular carcinoma and were associated with hepatitis C infection. In one of these cases, the hepatitis C infection had been successfully controlled (hepatitis C titers were undetectable for 1 year before he presented with spinal cord compression). This occurrence in a Native American with a controlled hepatitis C infection has not been reported previously. CONCLUSIONS: Primary care physicians, oncologists, and gastroenterologists should be cognizant of this unusual presentation of hepatocellular carcinoma in a Native American. Such knowledge may help improve early diagnosis and survival.

Alectinib (Alecensa)-induced reversible grade IV nephrotoxicity: a case report and review of the literature.

BACKGROUND: Lung cancer is among the top causes of cancer-related mortality in men and is the second most common cancer after breast cancer in women. There are approximately 234,030 new cases of lung cancer and 154,050 deaths from lung cancer in 2018 as per the latest American Cancer Society's report. Alectinib, a more potent orally active tyrosine kinase inhibitor which was approved by the US Food & Drug Administration for anaplastic lymphoma kinase-positive lung adenocarcinoma, has been shown to have a reasonable safety profile when compared with other anaplastic lymphoma kinase-targeted therapy. As per research studies, grade 1 or 2 renal impairment has been reported but grade 4 renal toxicity due to alectinib has not been reported so far. We report a case of acute renal failure caused by alectinib which necessitated emergency dialysis. This is the first case report describing the severe renal toxicity of alectinib. CASE PRESENTATION: We describe a case of 72-year-old Taiwanese man diagnosed with stage IV anaplastic lymphoma kinase-positive adenocarcinoma of the lung initially treated with crizotinib for over a year, which was switched to alectinib due to disease progression with brain metastasis. Within 6 weeks of starting alectinib, he developed acute renal failure needing emergency dialysis support. His renal failure was secondary to acute tubular necrosis and had a complete reversal within 7-10 days on withdrawing the medication. When he was re-challenged with alectinib, his creatinine started to worsen again which confirmed the renal toxicity of alectinib. CONCLUSIONS: This case emphasizes the uncommon adverse effect of the anaplastic lymphoma kinase-targeted therapy alectinib causing acute renal failure manifesting as acute tubular necrosis. Recognition of alectinib nephropathy requires a thorough drug history and knowledge of risk factors that lessen its margin of safety at therapeutic ingestions. Frequent monitoring of renal functions and early nephrology referral significantly reduce the mortality and morbidity of these patients.

Gamma-delta (γδ) T-cell lymphoma - another case unclassifiable by World Health Organization classification: a case report.

BACKGROUND: We present a case of gamma-delta T-cell lymphoma that does not fit the current World Health Organization classifications. CASE PRESENTATION: A 74-year-old Caribbean-American woman presented with lymphocytosis, pruritus, and non-drenching night sweats. Bone marrow and peripheral blood analyses both confirmed the diagnosis of gamma-delta T-cell lymphoma. An axillary lymph node biopsy was negative for lymphoma. Clinically absent hepatosplenomegaly and skin lesions with biopsy-proven gamma-delta T-cell lymphoma suggest that she is unclassifiable within the current classification system. CONCLUSIONS: We believe this is a case of not otherwise specified gamma-delta T-cell lymphoma. Accumulation of these rare not otherwise specified cases will be important for future classification which further defines the biology of this disease.

A Case Report of Primary Nasal Natural Killer (NK)/T-Cell Lymphoma in an African American Patient Presenting with Hemophagocytic Syndrome.

BACKGROUND Extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is generally an aggressive and rare non-Hodgkin lymphoma. It is most common in East Asians, Native Americans, and South Americans, but is rarely reported in blacks. CASE REPORT A 55-year-old African American male born in Grenada presented with a left nostril mass with facial swelling and biopsy subsequently confirmed a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKTCL). Immunochemistry was positive for CD2, cytoplasmic CD3, CD7, CD 43, CD 56, granzyme B, and TIA-1. In situ hybridization was positive for Epstein-Barr virus encoded ribonucleic acid (EBERs). Bone marrow aspiration did not show lymphoma involvement. The patient had progressive neutropenia upon presentation, with further investigations showing hepatomegaly, hyperferritinemia, and hemophagocytosis in the bone marrow. We reached a diagnosis of hemophagocytic syndrome. He was treated with a high-dose combination chemotherapy and radiation therapy; the neutropenia improved significantly with steroids as treatment for immune activation in the setting of hemophagocytic syndrome. CONCLUSIONS To the best of our knowledge, this is the only second report of extranodal NK/T-cell lymphoma, nasal type in a black patient, and it raises the awareness of early recognition of rare manifestations of NK/T-cell lymphoma such as hemophagocytic syndrome.

Quantification of IGF-1 Receptor May Be Useful in Diagnosing Polycythemia Vera-Suggestion to Be Added to Be One of the Minor Criterion.

Endogenous erythroid colony (EEC) formation is one of the minor criteria for diagnosing polycythemia vera (PV) according to 2008 WHO diagnostic criteria. But EEC requires bone marrow aspiration and sophisticated laboratory procedures; therefore, practically it is rarely used to diagnose PV. Insulin-like growth factor 1 receptor (IGF-1R) was found to be constitutively phosphorylated and was responsible for the EEC formation in PV; therefore, we measured IGF-1R levels in the peripheral blood of 26 PV patients and compared them with those of 33 patients with secondary polycythemia and 29 normal controls. Among the PV patients, 16 were treated with only phlebotomy, 9 received hydroxyurea, and 1 was treated with ruxolinitinib. We found that PV patients treated with only phlebotomy had significantly higher IGF-1R levels than did those PV patients treated with hydroxyurea or ruxolinitinib. None of the secondary PV patients or normal controls had elevated IGR-1R levels, while 14 of 16 (87%) PV patients had significantly elevated IGF-1R levels. The new 2016 WHO has eliminated EEC as a minor criterion for diagnosing PV, but there are still some cases that cannot be definitively diagnosed by the current criteria. Therefore, we suggest that quantifying the IGF-1R level in peripheral blood by flow cytometry to replace EEC as the minor criterion for diagnosing PV.

Nuclear protein in testis midline carcinoma of larynx: An underdiagnosed entity.

BACKGROUND: Nuclear protein in testis (NUT) carcinomas are very rare and have a very poor survival rate. The most common sites of involvement include the nasal cavity, sinus, and mediastinum. Laryngeal NUT midline carcinoma is extremely rare, with only 2 cases reported thus far. Here, we are describing another case of NUT laryngeal carcinoma. METHODS AND RESULTS: The patient was a light smoker and nondrinker who presented with upper respiratory tract obstruction. Imaging and laryngoscopic evaluation revealed a large intraluminal laryngeal mass. Biopsy demonstrated poorly differentiated carcinoma with intact mucosa and only focal coexpression of CK5/6 and p40. NUT protein immune-stain positivity conclusively established the diagnosis of NUT midline carcinoma. CONCLUSION: Absence of well-known risk factors, pathologic finding of lack of mucosal involvement and lack of squamous differentiation with poorly differentiated carcinoma, should prompt clinicians to consider this rare entity as a possible diagnosis. © 2016 Wiley Periodicals, Inc. Head Neck 38:E2471-E2474, 2016.

Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα.

Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis.