Browsing by Author "Grider, Douglas J."

Now showing 1 - 20 of 23
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    An Alarming Mimicry of Intra-Abdominal Infections: Acute Appendiceal Diverticulitis
    Kim, Youseung; Kesar, Varun; Grider, Douglas J.; Chitnavis, Maithili V. (Hindawi, 2021-11-12)
    A 65-year-old woman presented with three days of colicky abdominal pain. Abdominal imaging illustrated small bowel enteritis, ascites in both paracolic gutters, and incidental hepatic steatosis. Although ascites fluid demonstrated high neutrophil count consistent with peritonitis and the patient received adequate antibiotics, she clinically deteriorated. Subsequent exploratory laparotomy revealed necrotic appendix and multiple intra-abdominal abscesses. Histopathology showed acute suppurative appendicitis with multiple other intact small diverticula, indicating likely perforation of inflamed appendiceal diverticula with subsequent abscess formation and abdominal peritonitis. This case highlights the importance of ascites fluid analysis and continued clinical correlation, especially in cases of rare entities with atypical presentations.
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    Assessing Presenting Symptoms, Co-Morbidities, and Risk Factors for Mortality in Underserved Patients with Non-Hereditary Early-Onset Colorectal Cancer
    Reddy, Shravani; Mouchli, Awf; Bierle, Lindsey; Gerrard, Miranda; Walsh, Christopher; Mir, Adil; Lebel, David P.; Mason, Christopher; Grider, Douglas J.; Rubio, Marrieth G. (Cureus, 2021-07-02)
    Background: The presenting symptoms and co-morbidities contributing to mortality in young patients (age < 50 years old) with colorectal cancer (CRC) are poorly understood. We reviewed these features in our patient population with non-hereditary early-onset CRC (EO-CRC). Study aim: This study aimed to assess characteristics of patients with a diagnosis of non-hereditary EO-CRC, including presenting symptoms and metabolic disorders contributing to mortality in underserved areas of southwest Virginia. Methods: In this retrospective observational study, we selected patients aged 18-50 years with a diagnosis of non-hereditary EO-CRC from 2008 to 2016 at Carilion Roanoke Memorial Hospital. The electronic medical record was queried to identify demographic data, medical history, histopathology results, lab values, and mortality. The cumulative risks of symptoms and co-morbid metabolic disorders was estimated using Kaplan-Meier curves. Results: We identified 139 patients with non-hereditary EO-CRC (mean age 41.6 ± 6.9 years). Almost half of these patients were obese (BMI > 30), 30.9% had a diagnosis of hypertension, 29% had hyperlipidemia (HLD), and 17.35% had diabetes mellitus type 2 (DM2). Diagnosis was delayed by 4.5 months from initial presentation, and 17% had advanced disease (stage III/IV). Also, 68.5% of patients were symptomatic with one to three symptoms, most commonly with rectal bleeding (45.3%). The chronicity of HLD (≥5 years) was associated with reduced survival in our patients with EO-CRC. The survival of females with multiple metabolic disorders was reduced compared to females with a single metabolic disorder. Conclusions: Multiple symptoms, chronic HLD, and female gender with multiple metabolic disorders were factors associated with poor outcomes in non-hereditary EO-CRC patients.
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    Bleeding Gastric Lipoma Resected by Endoscopic Submucosal Dissection
    Mir, Adil Shamim; Kesar, Varun; Sageer, Mohamed; Grider, Douglas J.; Chitnavis, Vikas (2020-06-29)
    Gastric lipomas are slow-growing benign lesions of the stomach that are often detected incidentally. Most cases are asymptomatic but larger lesions may become symptomatic, thereby requiring treatment. Multiple endoscopic modalities have been used for resection in the past. We present the case of a 67-year-old patient who presented with upper GI bleeding secondary to a gastric lipoma, which was successfully resected by endoscopic submucosal dissection.
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    A Case of Necrolytic Migratory Erythema (NME) Initially Misdiagnosed as Subacute Cutaneous Lupus Erythematosus (SCLE)
    Gushiken, Alexis C.; Bankole, Adegbenga A.; Croteau, Jeff S.; Grider, Douglas J. (Clinical Medical Reviews and Case Reports, 2018-10-31)
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    Diffuse Gastric Ganglioneuromatosis: Novel Presentation of PTEN Hamartoma Syndrome—Case Report and Review of Gastric Ganglioneuromatous Proliferations and a Novel PTEN Gene Mutation
    Williams, Alexander J.; Doherty, Emily S.; Hart, Michael H.; Grider, Douglas J. (Hindawi, 2018-03-25)
    Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis. A diagnosis of diffuse ganglioneuromatosis is relevant for patient care because, unlike sporadic polypoid ganglioneuromas or ganglioneuromatous polyposis, most are syndromic. Diffuse ganglioneuromatosis is commonly associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2b, and Cowden Syndrome, one of the phenotypes of PTEN hamartoma tumor syndrome. The patient had the noted gastric diffuse ganglioneuromatosis, as well as other major and minor criteria for Cowden syndrome. Genetic testing revealed a novel frameshift mutation in the PTEN gene in the patient, her father, paternal aunt, and the aunt’s son who is a paternal first cousin of the patient.
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    Epidermoid Cysts in a Wandering Spleen: An Unusual Enigma
    Algino, Sarah E.; Sorrentino, Siena; Luyimbazi, David T.; Grider, Douglas J. (Hindawi, 2019-11-20)
    Epidermoid splenic cysts are rare lesions in the spleen. These cysts are characterized by a stratified squamous epithelial lining, internal septations, and calcification. Congenital in origin, epidermoid splenic cysts are postulated to arise from misfolding and mesothelial cell incorporation into the splenic parenchyma. This report presents a unique case of an 18-year-old woman with an epidermoid splenic cyst in a congenital wandering spleen. Computed tomography and transabdominal ultrasound imaging along with immunochemistry staining confirmed the diagnosis. To the authors’ knowledge, this is the first reported case of an epidermoid cyst in a wandering spleen.
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    Gastric Outlet Obstruction Secondary to Metastatic Breast Carcinoma 25 Years After Initial Diagnosis: A Mimic of Primary Gastric Carcinoma
    Abel, William; Ganjineh, Brandon; Reddy, Shravani; Gohil, Vishal V.; Yeaton, Paul; Grider, Douglas J. (Lippincott, Williams & Wilkins, 2022-12-26)
    Although breast cancer is the most common form of cancer in women, metastasis to the stomach is incredibly rare. Gastric metastasis of breast cancer has been described in the literature, with an estimated median of 6 years from the initial diagnosis of primary breast cancer to metastasis and multiple instances greater than 10 years. In this case, a patient presented with gastric outlet obstruction in the setting of breast cancer metastasis to the pylorus 25 years after the original diagnosis.
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    Iatrogenic Leptomeningeal Carcinomatosis Following Craniotomy for Resection of Metastatic Serous Ovarian Carcinoma: A Systematic Literature Review and Case Report
    Stopa, Brittany M.; Cuoco, Joshua A.; Adhikari, Srijan; Grider, Douglas J.; Rogers, Cara M.; Marvin, Eric A. (Frontiers, 2022-04-25)
    Metastasis of ovarian carcinoma to the central nervous system occurs in <2% of cases and classically localizes within the brain parenchyma. Moreover, leptomeningeal spread of these tumors is an exceedingly rare phenomenon. Here, we conduct a systematic review of the current literature on the natural history, treatment options, and proposed pathogenic mechanisms of leptomeningeal carcinomatosis in ovarian carcinoma. We also report a case of a 67-year-old female with stage IV metastatic ovarian serous carcinoma initially confined to the peritoneal cavity with a stable disease burden over the course of three years. Follow-up imaging demonstrated an intracranial lesion, which was resected via craniotomy, and pathology was consistent with the original diagnosis. Three months after surgery, she developed rapidly progressive dizziness, generalized weakness, fatigue, and ataxia. Repeat MRI demonstrated interval development of extensive and diffusely enhancing dural nodularity, numerous avidly enhancing supratentorial and infratentorial lesions, enhancement of the bilateral trigeminal nerves, internal auditory canals, and exit wound from the surgical site into the posterior aspect of the right-sided neck musculature consistent with diffuse leptomeningeal dissemination. The present case highlights that leptomeningeal dissemination of ovarian carcinoma is a potential yet rare consequence following surgical resection of an ovarian parenchymal metastasis. Progressive clinical symptomatology that develops postoperatively in this patient population should prompt urgent workup to rule out leptomeningeal disease and an expedited radiation oncology consultation if identified.
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    Interstitial Mycosis Fungoides: An Unusual Mimic of Interstitial Granuloma Annulare Not to Miss
    Singh, Neha; Fagan, Kiley K.; Grider, Douglas J. (Hindawi, 2022-09-05)
    Interstitial mycosis fungoides is a rare histopathologic variant of mycosis fungoides that may resemble interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Reported is a case of a 62-year-old African American female who presented with an asymptomatic, progressive rash of the left underarm and abdomen with histologic features suggestive of granuloma annulare. Biopsies revealed an interstitial pattern of cells in the dermis with prominent small aggregates of atypical lymphocytes, a few atypical lymphocytes in the lower epidermis, and a mild increase in dermal mucin. Immunohistochemistry staining revealed the atypical lymphocytes to be positive for CD3 and CD8 and negative for CD4 and CD7, an aberrant immunoprofile. Mixed in the dermis with the atypical lymphoid cells were a few CD68 positive histiocytes and S100 protein positive dermal dendritic cells. T-cell receptor beta gene rearrangement studies showed nearly the same clonal peaks for TCRB rearrangement in two biopsy specimens from separate sites, all supporting a diagnosis of interstitial mycosis fungoides. The patient is undergoing treatment with full body narrowband UVB (nbUVB) phototherapy with notable improvement in skin discoloration and resolution of several abdominal lesions. A diagnosis of interstitial mycosis fungoides is challenging to make based on clinical features alone and is often clinically misdiagnosed. Awareness of histopathologic features is critical to make an accurate diagnosis and thus patient management.
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    McArdle Disease vs. Stiff-Person Syndrome: A Case Report Highlighting the Similarities Between Two Rare and Distinct Disorders
    Godbe, Kerilyn; Malaty, Giovanni; Wenzel, Alyssa; Nazeer, Sahana; Grider, Douglas J.; Kinsey, Adrienne (2020-11-10)
    McArdle disease is a rare autosomal recessive disorder of muscle glycogen metabolism that presents with pain and fatigue during exercise. Stiff-Person Syndrome is an autoimmune-related neurologic process characterized by fluctuating muscle rigidity and spasm. Reported is a 41-year-old male who presented to the emergency department due to sudden-onset weakness and chest pain while moving his refrigerator at home. Cardiac workup was non-contributory, but a creatine kinase level > 6,000 warranted a muscle biopsy. The biopsy pathology report was misinterpreted to be diagnostic for McArdle disease given the clinical presentation. After 4 years of treatment without symptomatic improvement, a gradual transition of symptoms from pain alone to pain with stiffness was noted. A positive glutamic acid decarboxylase antibody test resulted in a change of diagnosis to Stiff-Person Syndrome. This is the first known case that highlights the similarities between these two rare and distinct disease processes, highlighting the necessity for thorough history taking, maintenance of a broad differential diagnosis, and knowledge of how best to interpret complex pathology reports.
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    Metastatic Multiple Myeloma to the Skin
    Holliday, Alex C.; Khan, Mohammed I.; Mazloom, Sean E.; Chavan, Rahul N.; Grider, Douglas J. (Hindawi, 2019-11-12)
    Cutaneous involvement of multiple myeloma (MM) is uncommon, typically occurs in late stage disease, and is a poor prognostic indicator with an approximate eight month median survival. We present a 51-year-old man with relapsed lambda light chain MM who developed abrupt asymptomatic skin metastases. Biopsy revealed a dermis replete of atypical plasma cells, positive for CD138 and CD45. In situ hybridization confirmed lambda light chain restriction. Despite rescue antimyeloma therapy with the anti-CD38 drug daratumumab, he rapidly declined clinically and succumbed to the disease four weeks after presentation. A standard treatment approach for cutaneous MM does not currently exist; however, various techniques to detect cytogenetic abnormalities are emerging and will provide additional prognostic value and direct individualized therapy.
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    Metastatic Plasmacytoid Urothelial Carcinoma Masquerading as a Primary Signet Ring Cell Carcinoma of the Duodenum
    Mir, Adil S.; Mouchli, Mohamad; Lebel, David P.; Grider, Douglas J. (Springer, 2023-08)
    Plasmacytoid urothelial carcinoma can histologically mimic gastrointestinal signet ring cell carcinoma, a potential diagnostic pitfall resulting in improper clinical management. We present a rare case of a malignant duodenal ulcer due to metastasis from plasmacytoid urothelial carcinoma. Only by histological and retrospective immunohistochemical comparison with the primary bladder tumor was this revealed as a metastasis from a plasmacytoid urothelial carcinoma. This case report highlights the importance of clinical correlation and comparison with any previous pathology specimens, the limitations of immunohistochemical staining, and the utilization of both old and new immunohistochemical tools when differentiating signet ring cell carcinomas of primary sites versus potential metastases.
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    Neurofibroma with glomus-like bodies: A novel association-Thoughts about origin
    Patel, Riya T.; Rizzo, Marissa T.; Guerra, Karla C.; Grider, Douglas J. (Wiley, 2024-05-03)
    A neurofibroma with focal glomus-like body differentiation is an unusual phenomenon recently encountered in an excision specimen from the right lateral distal forearm of a 26-year-old man. Glomus cells are modified smooth muscle cells normally present in glomus-like bodies but can also be found in glomus tumors (GT) or lesions considered in the spectrum of GT, including myopericytoma, myofibroma, and angiolipoma. Neurofibromas are peripheral nerve sheath tumors derived from the neural crest cells. While both GT and its variants and neurofibroma are thought to be derived from different cell types, there is growing evidence that glomus cells have a neural crest origin. This is based on multiple theories, with some overlapping pathways, including neural crest cell differentiation, Schwann cell reprogramming, VEGF expression, and NF1 gene biallelic inactivation. This report adds to the growing evidence of possible neural crest origin for glomus cells and would help explain finding glomus-like bodies scattered through a neurofibroma.
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    Noncanonical NF-kappa B Signaling Upregulation in Inflammatory Bowel Disease Patients is Associated With Loss of Response to Anti-TNF Agents
    Nguyen, Vu Q.; Eden, Kristin; Morrison, Holly A.; Sammons, Megan B.; Knight, Kristin K.; Sorrentino, Siena; Brock, Rebecca M.; Grider, Douglas J.; Allen, Irving C.; Sorrentino, Dario (2021-06-10)
    Objectives: Targeting tumor necrosis factor (TNF) with biologic agents, such as infliximab and adalimumab, is a widely used and effective therapeutic strategy in inflammatory bowel disease (IBD). Unfortunately, a significant number of patients fail to respond or lose response over time to these agents. Previous studies have defined multiple complex roles for canonical NF-kappa B signaling in the pathogenesis of IBD. However, preliminary evidence suggests that the lesser defined noncanonical NF-kappa B signaling pathway also contributes to disease pathogenesis and response to anti-TNF agents. The objective of this study was to evaluate this hypothesis in Crohn's disease (CD) and ulcerative colitis (UC) patients. Design: A total of 27 subjects with IBD (19 with CD and 8 with UC) and 15 control subjects were tested. Clinical criteria, patient history, and endoscopic disease activity were factors used to categorize patients and define therapeutic response. Biopsy specimens were collected during colonoscopy and expression was determined for 88 target genes known to be associated with noncanonical NF-kappa B signaling and IBD. Results: Noncanonical NF-kappa B signaling was significantly upregulated in IBD patients and was associated with increased gastrointestinal inflammation, epithelial cell death, lymphocyte migration, and Nod-like receptor signaling. Furthermore, noncanonical NF-kappa B signaling was further upregulated in patients unresponsive to anti-TNF agents and was suppressed in responsive patients. MAP3K14, NFKB2, CCL19, CXCL12, and CXCL13 were significantly dysregulated, as were genes that encode pathway regulators, such as CYLD, NLRP12, and BIRC2/3. Conclusion: Our study identifies a previously uncharacterized role for the understudied noncanonical NF-kappa B signaling pathway in the pathogenesis of IBD and anti-TNF therapy responsiveness. The genes and pathways identified may ultimately prove useful in IBD management and could potentially be used as biomarkers of drug response.
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    A Novel Cause of Bowel Obstruction in a Patient with Long-Standing Crohn’s Disease
    Vedula, Satya V.; Nickerson, T. Paul; Grider, Douglas J. (Hindawi, 2021-10-18)
    Solitary fibrous tumors are rare tumors of mesenchymal origin. Although most often observed in the lung pleura, they have been reported in varied extrapleural sites. A 70-year-old male with complicated Crohn’s disease presented with 3 days of nausea, emesis, constipation, and abdominal pain. Computed Tomography (CT) demonstrated mucosal thickening of the middescending colon, consistent with fibrosing stricture. Surgical excision revealed an unusual, 5 cm mass originating in the subserosa. Histopathology of the lesion was notable for a proliferation of cells with spindle and stellate-shaped nuclei and no appreciable mitotic figures, which extended into the muscularis and submucosa. Immunohistochemistry was STAT6 nuclear positive and cytoplasmic CD34 positive, diagnostic for solitary fibrous tumor (SFT). In this case, the SFT infiltrating into the muscularis propria and subserosa caused the stricture and bowel obstruction. This illustrates that while fibrosing strictures are usually the etiology of bowel obstruction in the setting of Crohn’s disease, other rare possible causes should be considered.
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    Pancreatic Inflammatory Pseudotumor-Like Follicular Dendritic Cell Tumor
    Mograbi, Madison; Stump, Michael S.; Luyimbazi, David T.; Shakhatreh, Mohammad H.; Grider, Douglas J. (Hindawi, 2019-12-05)
    Follicular dendritic cell sarcoma (FDCS) is a rare and underdiagnosed malignant neoplasm which characteristically presents as a solitary, slow-growing mass with no discrete symptoms. Histologically, lymphocytes and spindle cells featuring large nucleoli in a whorled pattern are usually seen. FDCS is classically found in cervical and axillary lymph nodes, with occasional involvement of extranodal sites. Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDCT) is an uncommon subcategory of this neoplasm, demonstratively linked to the Epstein-Barr virus (EBV). This neoplasm can present similarly to FDCS, but systemic symptoms may be seen. Although, often found in the spleen and occasionally the liver, IPT-like FDCT has not previously been described within the pancreas. Presented, is an IPT-like FDCT of the pancreas and spleen of a 70 years old woman. Histologic features include variably sized geographic suppurative granulomas with chronic inflammatory cells and an atypical spindle cell proliferation with prominent nucleoli. Positivity for CD45 and CD68 in the larger spindled cells points to an inflammatory pseudotumor subtype and co-expression of CD21, CD23, and CD35 were indicative of follicular dendritic differentiation. The pseudotumor additionally demonstrated EBV-encoded RNA (EBER) positivity typical of IPT-like FDCT. Differentiation between inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) is additionally discussed.
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    Papuloerythroderma of Ofuji in a Young Man
    Patel, Raj H.; Fagan, Kiley; Chitnavis, Padma V.; Grider, Douglas J. (Springer, 2023-03-23)
    Papuloerythroderma of Ofuji (PEO) is a rare skin disorder characterized by a distinctive pattern of pruritic, flat-topped, erythematous papules which coalesce into an erythroderma-like eruption with classic sparing of the skin folds. Although the pathogenesis of this condition is incompletely understood, previous reports have suggested a notable link between PEO and various forms of malignancy and immunocompromised states. Here, we report a case of a healthy young male with no comorbidities who presented with the classical features of PEO that responded well to combination therapy comprised of topical corticosteroids and phototherapy.
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    Patient Derived Xenografts Expand Human Primary Pancreatic Tumor Tissue Availability for ex vivo Irreversible Electroporation Testing
    Brock, Rebecca M.; Beitel-White, Natalie; Coutermarsh-Ott, Sheryl; Grider, Douglas J.; Lorenzo, Melvin F.; Ringel-Scaia, Veronica M.; Manuchehrabadi, Navid; Martin, Robert C. G.; Davalos, Rafael V.; Allen, Irving C. (2020-05-22)
    New methods of tumor ablation have shown exciting efficacy in pre-clinical models but often demonstrate limited success in the clinic. Due to a lack of quality or quantity in primary malignant tissue specimens, therapeutic development and optimization studies are typically conducted on healthy tissue or cell-line derived rodent tumors that don't allow for high resolution modeling of mechanical, chemical, and biological properties. These surrogates do not accurately recapitulate many critical components of the tumor microenvironment that can impact in situ treatment success. Here, we propose utilizing patient-derived xenograft (PDX) models to propagate clinically relevant tumor specimens for the optimization and development of novel tumor ablation modalities. Specimens from three individual pancreatic ductal adenocarcinoma (PDAC) patients were utilized to generate PDX models. This process generated 15-18 tumors that were allowed to expand to 1.5 cm in diameter over the course of 50-70 days. The PDX tumors were morphologically and pathologically identical to primary tumor tissue. Likewise, the PDX tumors were also found to be physiologically superior to other in vitro and ex vivo models based on immortalized cell lines. We utilized the PDX tumors to refine and optimize irreversible electroporation (IRE) treatment parameters. IRE, a novel, non-thermal tumor ablation modality, is being evaluated in a diverse range of cancer clinical trials including pancreatic cancer. The PDX tumors were compared against either Pan02 mouse derived tumors or resected tissue from human PDAC patients. The PDX tumors demonstrated similar changes in electrical conductivity and Joule heating following IRE treatment. Computational modeling revealed a high similarity in the predicted ablation size of the PDX tumors that closely correlate with the data generated with the primary human pancreatic tumor tissue. Gene expression analysis revealed that IRE treatment resulted in an increase in biological pathway signaling associated with interferon gamma signaling, necrosis and mitochondria dysfunction, suggesting potential co-therapy targets. Together, these findings highlight the utility of the PDX system in tumor ablation modeling for IRE and increasing clinical application efficacy. It is also feasible that the use of PDX models will significantly benefit other ablation modality testing beyond IRE.
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    Persistent diarrhea with petechial rash - unusual pattern of light chain amyloidosis deposition on skin and gastrointestinal biopsies: A case report
    Bilton, Shawna E.; Shah, Nikhil; Dougherty, Diana; Simpson, Sarah; Holliday, Alex; Sahebjam, Farhad; Grider, Douglas J. (Baishideng, 2022-10-06)
    BACKGROUND Amyloidosis is a rare disease characterized by extracellular deposition of misfolded protein aggregated into insoluble fibrils. Gastrointestinal involvement in systemic amyloidosis is common, but is often subclinical or presents as vague and nonspecific symptoms. It is rare for gastrointestinal symptoms to be the main presenting symptom in patients with systemic amyloidosis, causing it to be undiagnosed until late-stage disease. CASE SUMMARY A 53 year-old man with diarrhea, hematochezia, and weight loss presented to a community hospital. Colonoscopy with biopsy at that time was suspicious for Crohn disease. Due to worsening symptoms including nausea, vomiting, and a new petechial rash, an abdominal fat pad biopsy was done. The biopsy showed papillary and adnexal dermal amyloid deposition, in a pattern usually seen with cutaneous amyloidosis. However, Cytokeratin 5/6 was negative, excluding cutaneous amyloidosis. The patterns of nodular amyloidosis, subcutaneous amyloid deposits and perivascular amyloid were not seen. Periodic Acid-Schiff stain was negative for lipoid proteinosis, Congo red was positive for apple green birefringence on polarization and amyloid typing confirmed amyloid light chain amyloidosis. Repeat endoscopic biopsies of the gastrointestinal tract showed amyloid deposition from the esophagus to the rectum, in a pattern usually seen in serum amyloid A in the setting of chronic inflammatory diseases, including severe inflammatory bowel disease. Bone marrow biopsy showed kappa-restricted plasma cell neoplasm. CONCLUSION Described is an unusual presentation of primary systemic amyloidosis, highlighting the risk of misdiagnosis with subsequent significant organ dysfunction and high mortality.
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    Posterior Reversible Encephalopathy Syndrome (PRES) and Drug-Induced Hypersensitivity Syndrome (DIHS) following Immunotherapy and BRAF/MEK Inhibition with Continued Response in Metastatic Melanoma
    Sabile, J. M.; Grider, Douglas J.; Prickett, K. A.; Hu, L.; Mallidi, P. V. (Hindawi, 2021-05-12)
    Background. The role of immunotherapy continues to evolve across both solid and hematologic malignancies. However, while use of immunotherapy has increased via the advent of checkpoint inhibition, chimeric antigen receptors, and vaccines against malignant cells, there remains uncertainty regarding the recognition and management of delayed immune-related reactions and post treatment immune-related sensitivity to subsequent medications, such as BRAF/MEK kinase inhibitors. Furthermore, it is unclear how immunotherapy may alter the adverse effect profile and efficacy of subsequent lines of treatment. Case Presentation. Discussed is a patient with stage IV metastatic melanoma who failed first-line treatment with a combination of nivolumab and ipilimumab. He was then treated with BRAF/MEK kinase inhibition via Encorafenib and Binimetinib. Shortly thereafter, the patient developed posterior reversible encephalopathy syndrome (PRES) and a generalized pruritic rash that was biopsied with consideration toward drug reaction versus drug-induced hypersensitivity syndrome (DIHS), formerly called drug reaction with eosinophilia and systemic symptoms (DRESS). The BRAF/MEK combination was held and steroid taper initiated with continued response even beyond conclusion of the steroid taper. Discussion and Conclusions. This case highlights the diagnostic challenge presented by PRES and DIHS in the setting of immunotherapy and BRAF/MEK kinase inhibition for malignant melanoma. The clinical rationale for reinitiating therapy following severe immune reactions subsequent to immunotherapy in the setting of relapsed/refractory metastatic melanoma is discussed. Additionally, the durable response our patient experienced throughout the drug hold period and steroid taper and its clinical potential etiologies and applications are reviewed. As checkpoint inhibition and tyrosine-kinase inhibitors have become cornerstones of cancer therapy, larger studies and long-term observations are needed to investigate the risks and benefits across different sequences of therapy.