Granulomatous Research Articles

Rectal Schistosomiasis and Adenocarcinoma

Abstract Introduction/Objective Schistosoma infestation has been implicated by the International Agency for Research on Cancer as an etiology for several cancers such as colon, liver, and bladder. S. japonicum is classified as a probable carcinogen in humans (class 2B). These trematodes may cause chronic infection in the affected organ leading to the trend of “inflammation-adenoma-carcinoma”. There is rising evidence that infection with Schistosoma japonicum is correlated with the liver and colorectal carcinoma in endemic Asian countries. We herein present a case of rectal adenocarcinoma associated with Schistosoma as a possible causal factor. Methods/Case Report An 88-year-old-woman from China, currently living in United States for past six years, presented with rectal bleeding. Colonoscopy showed evidence of a rectosigmoid mass 2.2 x 1.0 x 0.3 cm. She underwent trans-anal excision of the tumor. Microscopic examination showed moderately differentiated adenocarcinoma with tumor invading the muscularis propria (pT2). There were numerous oval / round calcified eggs (30 - 46 microns) with minute subterminal or no spine morphologically consistent with Schistosoma japonicum associated with granulomatous and foreign body giant cell reaction, fibrosis, and tissue eosinophilia. She was treated with Praziquantel and is currently undergoing endoscopic surveillance for recurrence. Results (if a Case Study enter NA) N/A Conclusion Patients with chronic Schistosoma japonicum infection have 3 times increased risk of developing colorectal cancer than those with no previous exposure to schistosomal infection. We believe that chronic S. japonicum infection is the likely etiology of rectal cancer in our patient. Physicians should be aware of such associations, especially for immigrants from endemic areas, to facilitate accurate diagnosis and management.

Evaluating CD1a Immunohistochemistry for Tegumentary Leishmaniasis Diagnosis in the New World: A Focus on Colombia.

Leishmaniasis, a chronic vector-borne disease caused by parasites of the genus Leishmania, presents diagnostic challenges. Conventional diagnostic methods struggle with accurate visualization of these parasites. Immunostaining with CD1a has demonstrated effectiveness in visualizing Leishmania parasites, particularly in the Old World. However, the application of CD1a immunostaining in Colombian leishmaniasis remains unexplored. To determine the utility of CD1a as an immunomarker in detecting chronic forms of tegumentary leishmaniasis. This proof-of-concept study involved 48 paraffin-embedded samples categorized into 3 groups: moderate-to-high parasite load (n = 15), low load (n = 15), and chronic granulomatous inflammation (n = 13); 5 samples diagnosed with cutaneous histoplasmosis. These samples were stained with the immunomarker CD1a clone EP3622 for comparative analysis. In addition, CD1a immunohistochemistry was compared with 18S rDNA qPCR and hematoxylin-eosin staining to evaluate its performance in relation to these established methods. CD1a immunohistochemistry was positive in 46.51% of the samples evaluated. This immunomarker showed lower sensitivity and negative predictive value than 18S rDNA qPCR and hematoxylin-eosin staining; specificity and negative predictive value were consistent. ROC indicated inferior discrimination for leishmaniasis compared with 18 s rDNA qPCR and hematoxylin-eosin staining. Immunohistochemistry for CD1a could be a diagnostic support in the detection of chronic forms of tegumentary leishmaniasis.

Decidual Granulomas in Placenta: A unique finding in Preeclamptic Pregnancy

Abstract Introduction/Objective Decidual granulomatous inflammation is a rare finding in the placenta, scarcely reported in the literature. We present an unusual case of a young woman with severe preeclampsia and histological presence of decidual granuloma, involving the placental membranes. Methods/Case Report A 34-year-old female, Gravida 2 Para 1, with prior term vaginal delivery without significant history presented at 26 weeks and 6 days of gestational age with decreased fetal movements. Her home blood pressure was 170 mm of Hg systolic and on presentation, was consistently within the range of <a href=“tel:192- 197/94-97”>192-197/94-97</a> mm of Hg. Biophysical profile of the fetus was 2/10. Complete blood count showed leukocytosis with absolute neutrophilia and urinalysis revealed slight increase in urine protein/creatinine ratio. Clinical diagnosis of severe preeclampsia was made. After initial stabilization, the patient underwent Cesarean section resulting in a premature baby with an uneventful postoperative course. The placenta was sent for histopathological examination. Grossly, the placental disc showed unremarkable membranes with normal appearing fetal and maternal surfaces. Sectioning revealed a central 4.2 cm hemorrhagic area and six tan-white wedge-shaped nodules ranging from 0.8-1.8 cm, occupying approximately 5% and 40% of the maternal surface, respectively. Microscopic examination revealed patchy non-caseating granulomas limited to the decidua, patchy intra-placental hematomas, placental infarcts and chronic villitis. Other findings included scattered avascular villi, villous stromal vascular karyorrhexis, focally increased syncytial knots, and decidual arteriopathy. Gram stain, GMS and acid-fast stains yielded negative results, while immunohistochemical stain CD68 highlighted histiocytes in the granulomas. The final diagnosis of decidual granulomas including the aforementioned microscopic observations was made. Results (if a Case Study enter NA) NA Conclusion Though decidual granulomas are seen in association with infectious and rheumatologic disorders. They can also be observed in severe preeclampsia as in this setting; with unclear underlying pathogenesis, warranting a close follow-up of the newborn and the mother.

An idiosyncratic reaction to the synthetic biologic membrane on a surgical wound

Abstract Introduction/Objective Biodegradable temporizing matrix (BTM) is a synthetic polymer used to temporarily close wounds and aid the body in generating new tissue. BTM is applied to a debrided wound.BTM acts as a scaffold aiding the migration of granulation tissue into the matrix. Once the tissue is fully integrated throughout the BTM, the sealing membrane is removed. The matrix slowly deteriorates until fully absorbed at approximately 18 weeks. Methods/Case Report An 80-year-old woman with a past medical history of eczema, rheumatoid arthritis and gout presented with swelling of the left third metatarsal. Imaging showed an abscess which was eventually drained and cultured to show mycobacterium chelone. The patient was started on antibiotics for mycobacterium. On follow up she reported a nodule on left forearm recently increased in size. MRI on 9/28 showed abscess of the dorsal aspect of phalanx. She underwent surgical debridement 10/31 on her finger and the forearm nodule. After debridement a polynovo BTM graft was placed. Histopathology showed skin and subcutaneous tissue with necrotizing granulomas of the finger and the forearm. Cultures and stains for mycobacterium returned negative.The patient was subsequently followed up for wound healing. She reported nodules on the left forearm at the scar from previous surgical site which were biopsied. Histopathology showed granulomatous inflammation, rare foreign body giant cells, and birefringent material. The stains for Ziehl-Neelsen, Fite and Gomori’s Methenamine Silver for Urate Crystals were all negative excluding the possibility of gouty tophi or mycobacterium. Results (if a Case Study enter NA) NA Conclusion The complex history of the patient with mycobacterium, gout, the giant cell reaction and the unique appearing birefringent crystals presented a puzzling problem. Given the negative stain results for mycobacteria and the presence of birefringent (foreign) material, we deem these granulomas most likely an idiosyncratic reaction to the synthetic biologic membrane applied during her prior procedure. There are no known cases of giant cell reaction and similar morphology of birefringent (foreign) material in literature.

Pulse Granuloma in Esophagus; A Rare finding in Achalasia Patient: Case Report and Literature Review

Abstract Introduction/Objective Pulse granuloma is a granulomatous reaction to foreign body, most commonly to food material. This is clinically silent and incidental but may be confused for a mass like lesion. This can be found any location in gastrointestinal tract but most reported in oral cavity and colon. We herein report a rare case of pulse granuloma in esophagus with literature review of the entity. Methods/Case Report A 58-year-old male with history of achalasia, surgical history of Heller myotomy, hernia reduction, hiatoplasty, gastropexy, vagotomy, presented with recurrent stricture of the esophagogastric junction. The patient received multiple esophageal balloon dilatations in the past due to high esophageal sphincter pressure and was complicated by severe reflux associated with esophagitis and large hiatal hernia. He underwent subtotal esophagectomy due to dysphagia. Gross examination of the esophagectomy specimen showed multiple previous procedure scars and was opened to reveal firm yellow food particles impacting in the mucosa. Histological examination showed gastroesophageal junctional mucosa with ulceration and fibrosis of the muscularis propria. Pink ribbon like hyalinized foci with giant cell was found which stained negative for GMS, PAS and AFB, supporting the diagnosis of pulse granuloma. Literature search for key word ‘Pulse Granuloma’ identified thirty-five case reports from year 1977 to 2024, with most reported case in the oral cavity (14 cases, 42%). Out of ten cases reported in gastrointestinal tract, 1 case was reported in small bowel and 9 cases were reported in colon and rectum and no cases were reported in esophagus. Results (if a Case Study enter NA) NA Conclusion Our patient’s history of achalasia and dysphagia along with histopathologic findings supports diagnosis of pulse granuloma in esophagus. Although clinically silent, pulse granuloma may cause mass-like lesions and result in enlargement and stenosis. In setting of esophageal achalasia recognizing this entity is important as it can mimic malignancy and other mass-forming lesions.

Deep Fungal Infections of Skin and Role of Histopathology in Diagnosis

Abstract Introduction: Deep mycoses acquired by penetrating trauma to the skin can have varied and sometimes atypical morphological presentations resulting in diagnostic dilemmas and delay in treatment onset. Histopathology can be a useful tool in not only diagnosing but also differentiating various deep mycoses. Aims and Objectives: To observe various morphological presentations and histopathological features of deep fungal infections. Materials and Methods: A retrospective multi-centric study was conducted from 2010 to 2020 at 16 centres. The cases with diagnoses of various deep mycoses were included in the study. The patients presenting with cutaneous manifestations were included in the study. Their demographic details, history, presenting signs and symptoms, morphological presentations, histopathological features and treatment details were collected from the case sheets. Results: A total of 124 cases were found from the case records. The most common type was chromoblastomycosis (42) followed by mycetoma (28) and rhinosporidiosis (17). The mean age was 43.76 ± 5.44 years. The average duration of symptoms before presentation was between 2 months to 10 years (average 2.5 ± 1.33 years). Male to female ratio was 1:0.7. Prior history of trauma was recorded in 36% of cases. Chromoblastomycosis cases presented with verrucous to atrophic plaques with black dots on the surface and histopathology findings included pesudoepitheliomatous hyperplasia, epithelioid cell granulomas, copper penny bodies within granulomas and abscesses. Rhinosporidiosis cases had polypoid grape-like lesions in the nose and eyes most commonly with histopathology findings of abundant thick-walled sporangia in dermis packed with thousands of spores. Eumycetoma patients had pigmented, indurated swelling with multiple sinuses discharging black granules and histopathology showed dermal abscesses and foreign body granulomatous reaction with PAS-positive hyphae. Histoplasmosis patients presented with few to multiple nodulo-pustular lesions on skin and palatal ulcers while small basophilic bodies packed in the cytoplasm of histiocytes were noted in histopathology. Phaeohyphomycosis cases presented as deep-seated cystic lesions and biopsy revealed deepithelialized cysts in the dermis or hypodermis with lumen showing necro inflammatory debris and fungal hyphae. Sporotrichosis cases had erythematous, tender nodules and papules either as single lesions or as multiple lesions arranged in a linear fashion and histopathology showed pseudoepitheliomatous hyperplasia of epidermis, loose to well-defined epithelioid cell granulomas and microabscesses. Spores were found in two cases. Cryptococcosis patient had multiple umbilicated lesions resembling giant molluscum contagiosum loose epithelioid cell granulomas and medium-sized spores lying in both intra and extracellularly on histopathology. Penicilliosis patients had nodulo-pustular lesions and histopathology showed an admixture of histiocytes, epithelioid cells, plasma cells, lymphocytes and polymorphs in the dermis with the presence of yeast-like spores in the cytoplasm of histiocytes and epithelioid cells. Entomophthoromycosis cases presented with asymptomatic subcutaneous firm swelling with loss of skin pinchability. Conclusion: Though clinical findings of deep fungal infections are characteristic similar morphology and atypical presentations can be sometimes confusing. Histopathology is useful for confirming the diagnosis.

Borderline Lepromatous Leprosy Masquerading as Granuloma Annulare: A Case Report

Background: Leprosy is a chronic granulomatous disease caused by Mycobacterium Leprae. Leprosy is a great imitator with its various atypical, unusual and varying clinical presentations which can be confused with many infectious and non-infectious diseases. Case Report: A 46-year-old female presented to the dermatology department with complaints of painful raised lesions over face, upper back, upper limbs, lower legs and feet for 12 months. Clinically suspected as a case of Granuloma annulare. Punch biopsy was taken which revealed epidermis with dermis showing nodules of histiocytes and lymphocytes with grenz zone at the dermoepidermal junction. Acid fast stain and Fite Faraco stain was performed which revealed the presence of leprae bacilli with bacteriological index of 4+. Conclusion: Detailed history taking and correlating clinical picture with morphology is required to diagnose atypical presentations of leprosy. Early diagnosis helps to provide appropriate treatment and thus prevent from devastating complications.

Gene editing of NCF1 loci is associated with homologous recombination and chromosomal rearrangements

CRISPR-based genome editing of pseudogene-associated disorders, such as p47phox-deficient chronic granulomatous disease (p47 CGD), is challenged by chromosomal rearrangements due to presence of multiple targets. We report that interactions between highly homologous sequences that are localized on the same chromosome contribute substantially to post-editing chromosomal rearrangements. We successfully employed editing approaches at the NCF1 gene and its pseudogenes, NCF1B and NCF1C, in a human cell line model of p47 CGD and in patient-derived human hematopoietic stem and progenitor cells. Upon genetic engineering, a droplet digital PCR-based method identified cells with altered copy numbers, spanning megabases from the edited loci. We attributed the high aberration frequency to the interaction between repetitive sequences and their predisposition to recombination events. Our findings emphasize the need for careful evaluation of the target-specific genomic context, such as the presence of homologous regions, whose instability can constitute a risk factor for chromosomal rearrangements upon genome editing.

Granulomatous Inflammation on Neuropathology in Antibody-associated CNS Paraneoplastic Syndromes

Granulomatous Inflammation on Neuropathology in Antibody-associated CNS Paraneoplastic Syndromes

Granulomas in Common Variable Immunodeficiency Display Different Histopathological Features Compared to Other Granulomatous Diseases

Granulomatous disease affects up to 20% of patients with Common Variable Immunodeficiency (CVID). Granulomas are comprised of highly activated immune cells, and emerge in response to antigenic triggers. In CVID granulomas however, the underlying pathophysiology is unclear and the specific trigger remains unknown. Granuloma formation in CVID is often compared to sarcoidosis, although clinical context and prognosis differ, suggesting a different pathogenesis. The aim of this study was to investigate if the cellular organization and proteomics of granulomas in CVID is different from other granulomatous diseases. Therefore, tissue slides from formaldehyde fixed paraffin embedded biopsies obtained from patients with CVID, sarcoidosis, tuberculosis and foreign-material induced pseudo-sarcoidosis were stained with hematoxylin and eosin and assessed for histopathological characteristics. Targeted spatial protein analysis was performed, and immune fluorescent multiplex assays were used to analyze the cellular organization. Histological analysis revealed that CVID granulomas were smaller, less circumscribed, with fewer multinucleated giant cells and minimal fibrosis compared to the other granulomatous diseases. Spatial protein analysis showed that granulomas in all diseases expressed CD68, CD11c, CD44, CD127, and PD-L1. However in CVID, reduced expression of the fibrosis-related protein fibronectin, but enrichment of CD163, CD3 and FAPα inside CVID granulomas was observed. Immunofluorescence analysis conformed a different cellular organization in CVID granulomas with increased influx of neutrophils, macrophages, T and B lymphocytes. In conclusion, granulomas in CVID display a different histological and cellular organization with increased influx of myeloid and lymphoid cells, compared to sarcoidosis, tuberculosis and pseudo-sarcoidosis, indicating a distinct pathogenesis underlying granuloma formation.

Parasitic Infections and Host Tissue Response in Histopathology: A Rare Retrospective Research Study from Rural India.

Parasite are living organisms which survive on another living being for their nourishment and survival. When these parasites resides on human body, they bring about inflammatory response. This inflammatory response leads to tissue reaction. Tissue response on microscopy appear as an eosinophilia, abscess and granulomas. This study was planned with the objective to know the frequency of parasite infection, tissue response in parasite infection and its comparison in terms of variables like age, sex and the type of parasite. This is a retrospective study, conducted in the department of pathology. A total of 26 cases of parasitic infections in human specimens reported in our department from January 2008 to December 2019 were included in this study. On all archived cases hematoxylin and eosin and where ever required periodic acid schiff was applied. These slides were thoroughly examined and clinicopathological correlation was studied. Age range of patients was 5 years to 70 years. Maximum number of patients were belonging to 11-20 year age group. Male to female ratio was 1:2. Among the 26 cases, there were 9 cases (34.62%) of hydatid cyst, six cases of Entamoeba histolytica (23.07%), four cases of Enterobious vermicularis (15.38%), and two cases (7.69%) each of Ascaris lumbricoides, filaria and cysticercosis respectively. A specific tissue response seen in cysticercosis having chronic inflammatory cells, palisaded epithelioid cells granuloma and giant cell reaction while other showed inflammatory cells infiltration. Clinically diagnosis of parasitic infection in each and every case is not possible, similarly radiological investigation is also suggestive only. Histopathology examination is the benchmark investigation to diagnose parasite infection and tissue reaction to the host. Histopathology examination must be implicated in every case to identify parasite and tissue reaction so that the patients can be managed accordingly before the complications rises.

8126 PTH-Independent, Calcitriol-Mediated Hypercalcemia In Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

8126 PTH-independent, Calcitriol-mediated Hypercalcemia in Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

7027 A Rare And Multifactorial Etiology Of Severe Parathyroid Hormone Independent Hypercalcemia In An Adult Female With Rett Syndrome

Abstract Disclosure: M.I. Foo: None. M. Thompson: None. Background: Symptomatic hypercalcemia is a rare, but potentially life-threatening disorder. Although dehydration is an unusual cause of severe hypercalcemia, in the appropriate clinical setting dehydration may amplify underlying mild or moderate hypercalcemia to dangerous levels.Case: A 46-year-old non-verbal, non-mobile Caucasian female with Rett Syndrome (RS) with Stage III Chronic Kidney Disease (CKD3) who is dependent on percutaneous endoscopic gastrostomy (PEG) tube for nutrition and known PTH independent hypercalcemia of unknown etiology presented to the hospital with intractable vomiting and constipation, an outpatient serum calcium level of 16.0 mg/dL, and serum creatinine 4.03 mg/dL (baseline 1.2 mg/dL). Initial laboratory assessment revealed elevated corrected serum calcium levels (15.7 mg/dL), with appropriately suppressed PTH levels (12.5 pg/mL) and hypernatremia (146 mmol/L). Thyroid function tests, both Vitamin D 1,25(OH)2D and D 25(OH)D levels and PTH-RP were normal. Computed tomography of the abdomen and pelvis revealed bilateral nephrolithiasis and moderate stool burden, but no evidence of malignancy or granulomatous disease. Skeletal scintigraphy was also without evidence of osseous metastatic disease or Paget’s disease of bone. An in-depth interview with the patient’s caregiver uncovered that the patient had a relative intolerance to enteral hydration and had been receiving minimal water flushes prior to admission, contributing to severe dehydration. Hypercalcemia was ultimately ascribed to prolonged immobilization due to RS compounded by inadequate fluid intake and auto-diuresis secondary to hypercalciuria in the setting of CKD (prior baseline eGFR 45 mL/min/1.73m2).Outcome: The patient's hypercalcemia improved after a multidisciplinary and multi-directed approach involving intravenous and enteral fluid resuscitation, calcitonin, furosemide, and ultimately zoledronic acid following improvement in creatinine with fluid resuscitation. The dietary service employed a strategy of 24-hour enteral feeding, increasing both the frequency and amount of enteral water, which the patient tolerated well, and provided her with a new pump for home use. Education on monitoring tube feed tolerance and providing adequate enteral hydration was provided to both the caregiver and group home. On discharge, eGFR stabilized at 33 mL/min/1.73m2 and corrected calcium stabilized at 10.0–10.4 mg/dl. She was provided with an endocrinology follow-up to continue bisphosphonate therapy.Discussion: Hypercalcemia of immobility should remain a differential diagnosis in severe hypercalcemia, especially PEG tube dependent patients with underlying kidney disease. This case highlights the importance of thorough history taking and a multidisciplinary strategy to guarantee optimal care and mitigate potential adverse outcomes in medically complex patients. Presentation: 6/2/2024

7660 Navigating Hypercalcemia: MAC Treatment Hurdles and the Unforeseen Impact of Vitamin D Supplementation

Abstract Disclosure: S. Noguchi: None. S. Lai: None. A. Rajpal: None. Introduction: Hypercalcemia is a recognized complication in granulomatous disorders such as sarcoidosis and tuberculosis, resulting from increased 1 alpha-hydroxylase activity in macrophages leading to excessive conversion to 1,25(OH)2 vitamin D (calcitriol). Mycobacterium avium complex (MAC) is an infectious granulomatous disease often suspected in immunocompromised individuals, including those with human immunodeficiency virus (HIV). Additionally, vitamin D deficiency is prevalent in the general population, prompting supplementation. We hereby present a patient with advanced HIV and disseminated MAC who developed severe calcitriol-induced hypercalcemia in the setting of high dose vitamin D supplementation. Case description: A 48-year-old male with advanced HIV (CD4 count <20 cells/mm^3) presented for evaluation of abdominal pain and constipation, and was found to have severe hypercalcemia of 14.8 mg/dL. Five months prior, he had restarted anti-retroviral therapy (ART) after having been out of care for over a year and was diagnosed with disseminated MAC for which he was on azithromycin and ethambutol. Cultures drawn during this admission were negative for MAC. Hypercalcemia was possibly due to paradoxical immune reconstitution inflammatory syndrome (IRIS) and with appropriate management his calcium level rapidly normalized to 9.7 mg/dL and remained stable until the recent admission. He represented one year later with a calcium level of 13.8 mg/dL with suppressed parathyroid hormone levels, which was refractory to bisphosphonate therapy, therefore was empirically initiated on dexamethasone. By day 4, his calcium levels improved significantly and was discharged on a taper regimen. Cultures collected this admission later revealed ongoing MAC infection, which raised concern for treatment failure and calcitriol-induced hypercalcemia. Calcitriol levels were elevated at 105 pg/mL, which further supported this hypothesis. Additionally, prior to admission he had been prescribed ergocalciferol 50,000 units weekly for 8 weeks, after which he was transitioned to 2,000 units daily. This likely exacerbated the calcitriol-induced hypercalcemia by providing sudden availability of substrate, 25-OH vitamin D, for the activated macrophages. Conclusion: ART has reduced the incidence of opportunistic infections such as MAC, however mortality remains high. Vigilant monitoring for complications, particularly life-threatening calcitriol-induced hypercalcemia and timely use of corticosteroids, is crucial. This case also highlights the need for careful oversight in high-dose vitamin D supplementation for individuals with granulomatous disease and vitamin D dysregulation. Presentation: 6/2/2024

7183 Histoplasmosis Of Adrenal In An Immunocompetent Patient From Arizona: A Surprising Biopsy

Abstract Disclosure: R. Habibi: None. S. Penquite: None. N. Ebrahimi: None. R. Cardenas Lara: None. Introduction: Histoplasmosis of adrenal gland in the context of disseminated infection is a rare entity in a non-endemic area. Early diagnosis and treatment can save one’s life. Here we present a case of a patient from Arizona who was referred to us with a large adrenal mass initially resembling malignancy. Presentation: A 58-year-old male with no significant medical history from Bisbee Arizona presented to our clinic with significant weight loss of 120 pounds in 8months, jaundice, fatigue, nausea and vague abdominal pain. He had an abdominal CT scan in a rural area hospital which showed a left adrenal 4.2 x 4.3 x 3.7 cm mass with average HU=40, with interval development from a CT scan 6months prior to that which showed left adrenal 1.5 x 1.3 x 1.3 cm mass. He had the initial CT scan after a mechanical fall. He was experiencing sweating, dizziness and low blood pressure of 90/60 mmhg, but used to have hypertension. Physical examination revealed diffuse jaundice in an ill appearing cachectic individual. Laboratory data were significant for total bilirubin of 4.9, direct bilirubin 0.7. Plasma metanephrines and normetanephrines, 24-hour urine free cortisol, morning cortisol levels and DHEA sulfate were normal. Other findings on the CT scans of head, chest and abdomen were soft tissue thickening between the right posterior 10th and 11th ribs along with hepatosplenomegaly, nodular lung lesions with calcified granuloma, sub centimeter brain lesions within the left putamen/external capsule junction with corresponding mild edema. During the following month after initial visit he developed bilateral tongue masses with dysphagia along with enlarging bilateral adrenal lesions, measuring up to 4.4 cm on the right and 5.2 cm on the left. The patient was admitted to hospital for further extensive work up. He underwent biopsies of left adrenal mass and tongue lesions which demonstrated necrotizing granulomatous inflammation with fungal elements compatible with histoplasmosis. Liposomal amphotericin B was started, which was quickly switched to itraconazole 200mg twice a day once lumbar puncture result was normal. His transient low blood pressures resolved. He was seen in clinic after few weeks with overall improving symptoms. Follow up with imaging of adrenal in few months is planned. He is currently in his third month of treatment for histoplasmosis with itraconazole. Discussion: The presentation of disseminated histoplasmosis can resemble malignancy as illustrated in this case. Southwest of the United States is an unusual geographical area for such infection. Initial unilateral involvement of adrenal as a mass in an immunocompetent individual is also uncommon. Considering dramatic response to antifungal treatment, a clinician should suspect such rare infections when seeing a nonfunctional adrenal mass with rapidly progressive constitutional symptoms. Presentation: 6/3/2024

7200 A Unique Case Of Hypercalcemia From Primary Hyperparathyroidism With Thymoma And Concurrent Pulmonary Tuberculosis

Abstract Disclosure: S. Jing Hang Randy: None. L. Huiling: None. Background: Several case reports have reported the rare association of thymoma with primary hyperparathyroidism. We describe a unique case of hypercalcemia with such association but was also found to have concurrent pulmonary tuberculosis. Clinical Case: A 50-year-old Indian female with a significant history of anterior mediastinal mass underwent median sternotomy with mass resection and was found to have peri-operative hypercalcemia. Her only complaint was chronic cough. Initial investigations showed high adjusted calcium 2.78 mmol/L (2.15– 2.50 mmol/L), normal phosphate 1.1 mmol/L (0.8– 1.4 mmol/L) and high PTH 24.7 pmol/L (1.6– 6.9 pmol/L). Apart from the mediastinal mass, a whole-body CT scan showed multiple prominent mediastinal lymph nodes with non-specific subcentimetre lung nodules. The post-operative finding was a Type AB thymoma with necrotizing granulomatous inflammation in adjacent station I lymph node. Differentials for patient’s hypercalcemia included primary hyperparathyroidism, malignancies such as lymphomas and infectious causes in particular tuberculosis. Her 25-OH Vitamin D was low at 9 ug/L (30 - 100 ug/L), 1,25-dihydroxyvitamin D was elevated at 205 pg/mL (18-64 pg/mL) while creatinine, ALP, serum ACE and PTHrP were unremarkable. She was subsequently admitted for worsening hypercalcemia, fever and left pleural effusion with generalized lymphadenopathy where she underwent an Endobronchial Ultrasound-guided Transbronchial Needle Aspirate of station IV lymph nodes before being started on tuberculosis treatment. The AFB culture showed Mycobacterium Tuberculosis Complex thereafter. Parathyroid sonography revealed a 2.2cm x 0.9cm x 0.8cm lobulated hypoechoic lesion posterior to the inferior pole of left thyroid lobe. However, a confirmatory sestamibi scan could only be done 6 weeks post-thymectomy given the raw surgical bed, with a possibility of false-negative result for cervical parathyroid adenoma given a recent thymectomy. It subsequently showed a hyperfunctioning left inferior parathyroid nodule with no other suspicious focal uptake in the neck or mediastinum. Patient underwent a focused left parathyroidectomy. Histology showed features consistent with parathyroid adenoma. A stepwise trajectory of her calcium normalization was observed with hydration, intravenous zoledronic acid for her osteoporosis, tuberculosis treatment, adjuvant radiation therapy for her thymoma with margins involvement, and parathyroidectomy. Conclusion: This case illustrates the challenges faced while considering localizing scans for primary hyperparathyroidism with recent thymectomy given the common embryological origin of inferior parathyroid and thymus. It also demonstrates the possible co-existence of separate pathologies in hypercalcemia and the need to exercise prudent clinical judgement to further evaluate for these various etiologies. Presentation: 6/2/2024

5117 Unusual Sarcoid Presentation as a Case of Hypercalcemia

Abstract Disclosure: M. Salim: None. A. Chauhan: None. S. Avula: None. A. Ahmed: None. K. Zekarias: None. Background: Hypercalcemia may arise from a variety of causes and can pose challenging diagnostic dilemma. Clinical Case: An 89-year-old male presented with worsening malaise related to persistent hypercalcemia. He reported productive cough, polyuria, polydipsia, generalized muscle weakness and weight loss. Physical exam was remarkable for upper and lower extremities weakness. Laboratory tests showed calcium 11.6 (8.8-10.2 mg/dL), phosphorus 2.8 mg/dL (2.5-4.5 mg/dL), albumin 4.2 g/dL (3.5-5.2 g/dL), parathyroid hormone (PTH) 10 pg/mL (15-65 pg/mL), parathyroid hormone-related protein (PTH-rp) 4.5 pmol/L (0.0-2.3 pmol/L), TSH 6.24 (0.30 - 4.20 uIU/mL), free T4 1.10 ng/dL (0.90-1.70 ng/dL), GFR 61 mL/min/1.73m2, 25 OH Vit D 31 ng/mL (20-75 ng/mL), vit D 1,25-dihydroxy 134 pg/mL (19.9-79.3 pg/mL), calcium urine/creatinine 0.54. Hypercalcemia was first noted 11 months before the visit with a level of 14.0 mg/dL (8.8-10.2 mg/dL), phosphorus 3.5 mg/dL, PTH 11, PTH-rp 1.4 pmol/L, 25 OH Vit D 62 ng/mL, Vit D 1,25-dihydroxy 90 pg/mL, angiotensin-1-converting enzyme 12 U/L (16-85 U/L), serum and urine electrophoresis showed no monoclonal gammopathy present, and tuberculosis interferon-gamma test negative. Autoimmune workup was unremarkable, except for weak positive anti-signal recognition particle (SRP) antibodies and anti-Mi-2 antibodies. CT chest/pelvis/abdomen demonstrated peripheral predominant reticular opacities suggestive of interstitial lung disease and no malignant findings. Treatment history included zoledronic acid 11 months before the visit. The patient was referred for a granulomatous disease workup.Upon one month follow-up, the hypercalcemia symptoms were worsening. Repeat calcium was 12.3 mg/dL and fungal serologies were negative. The patient was started on prednisone empirically. PET CT was ordered and revealed patchy inflamed musculature of extremities suspicious of dermatomyositis/polymyositis. Further labs showed unremarkable myomarker panel, u3-Hydroxy-3-Methylglutaryl Coenzyme A reductase (HMGCR) antibody, Anti-cN-1A antibody, ACE 53 U/L, creatine kinase 32 U/L (39-309 U/L), aldolase 5.4 U/L (1.2-7.6 U/L), soluble IL-2R 1,021 U/mL (137-838 U/mL), and lysozyme 3.89 ug/mL (<2.75 ug/mL). A muscle biopsy was done, which showed benign skeletal muscle with patchy myofiber atrophy, patchy interstitial fibrosis, and focal interstitial mild chronic inflammation with no evidence of sarcoid granulomas in the sample. One week lab follow-up post initiation of steroid showed calcium of 10.1 mg/dL and subsequently improvement in his overall labs. Working diagnosis of sarcoid myositis was made. Conclusion: This case report highlights the approach of diagnosing a rare case of hypercalcemia due to sarcoid myositis. In a highly clinical suspicious patient, PET CT scan might be a necessary modality for diagnosis. Presentation: 6/2/2024

Extrapulmonary sarcoidosis

Sarcoidosis is a chronic disease of unknown origin that develops when a genetically susceptible host is exposed to an antigen, leading to an exuberant immune response characterized by granulomatous inflammation. Although lung involvement is almost universal as well as the leading cause of morbidity and mortality, virtually any organ can be affected. In particular, sarcoidosis of the heart, nervous system, and eyes can be devastating, leading to death, debilitation and blindness, and a multidisciplinary approach involving expert specialists is required for prompt diagnosis and appropriate treatment. Sarcoidosis of the skin can be disfiguring, thus posing a substantial psychologic and social impact on the patients. The diagnosis is often straightforward in the presence of compatible clinical manifestations in patients with biopsy-proven sarcoidosis, but is challenging when extrapulmonary signs/symptoms occur in isolation.Corticosteroids remain the first line therapy, with immunosuppressive or biologic agents being reserved to patients failing or experiencing side effects from steroids or developing refractory disease.

Overlap syndromes in sarcoidosis: Unveiling the masquerader

As a multi system granulomatous disease, clinical presentations of sarcoidosis are highly variable. In the absence of a stereotypical clinical presentation such as asymptomatic bilateral hilar adenopathy, Lofgren's syndrome, or lupus pernio, a diagnosis of sarcoidosis typically requires 1) compatible clinical presentation, 2) histologic evidence of granulomatous inflammation, and 3) the exclusion of other causes. The clinical presentation of sarcoidosis is often nonspecific and a variety of other causes of granulomatous inflammation can make diagnosing sarcoidosis a challenge for clinicians. “Overlap syndromes” are often used to describe clinical presentations of sarcoidosis that share histologic and clinical features of other diseases, or when the diagnosis of sarcoidosis is made in association with the coexistence of another diagnosis with similar clinical or histologic findings. Because of the risk of diagnostic delay and diagnostic errors, it is vital for clinicians to be familiar with overlap syndromes in sarcoidosis. The coexistence of sarcoidosis with other diseases can also significantly impact disease management and outcomes. This article will review the most current published data on overlap syndromes in sarcoidosis to aid clinicians in diagnosing and managing these complex patients.