Apple-green Birefringence Research Articles

880: PULMONARY AMYLOIDOSIS ASSOCIATED WITH B CELL LYMPHOPROLIFERATIVE DISORDER: A CASE REPORT

Introduction: Amyloidosis is caused by the deposition of misfolded autologous proteins in various organs and can be systemic or localized. AL amyloidosis is often associated with plasma cell disorder but here we report a rare case of Isolated Nodular Pulmonary Amyloidosis associated with a B cell Lymphoproliferative Disorder. Description: An 89 year old female with a past medical history of pulmonary arterial hypertension presented to the clinic with chronic stable exertional dyspnea and no associated symptoms. Four years prior, a computed tomography (CT) of the chest showed multiple bilateral calcified and noncalcified lung nodules with no further work-up. Chest X-ray performed at current presentation revealed extensive pulmonary reticulonodular shadowing at the peripheries with extensive fibrotic changes and scattered nodules. Subsequent CT chest showed interval increase of several bilateral nodules. A PET-CT showed multiple mildly hypermetabolic nodules. A CT guided needle biopsy of an FDG avid right upper lobe nodule measuring 1.5 x 1.4 cm was performed. Pathology was significant for homogenous acellular amorphous material with an entrapped plasma cell infiltrate. Congo red stain confirmed the presence of apple green birefringence diagnostic of amyloidosis. Immunohistochemistry showed a mixture of kappa-positive and lambda-positive cells, with kappa-positive cell predominance suggestive of an atypical plasma cell population. Clonal gene rearrangements were detected in both the immunoglobulin heavy chain and light chain gene which highly suggested the presence of a B-cell Lymphoproliferative Disorder. The patient was subsequently referred to oncology for further management. Discussion: Pulmonary Amyloidosis is an incidental radiological finding with patients being asymptomatic. CT chest may show lung nodules with/without calcifications. Biopsy is required for diagnosis with radiology guided fine needle aspiration. Isolated pulmonary amyloidosis has a good prognosis but should trigger evaluation for autoimmune disorders and B cell lymphoproliferative disorders as in this case with early referral and treatment of the underlying disorder.

Extensive Post-EMR Procedure Related Artifact due to Novel Submucosal Lifting Agent, Mimicking Amyloid – A Diagnostic Pitfall

Abstract Introduction/Objective Endoscopic mucosal resection (EMR) techniques are vital for the management of premalignant lesions and early-stage (T1N0) malignant lesions of the digestive tract. Recently FDA approved submucosal lifting agent “ORISE™” (Boston Scientific, Marlborough, MA) for EMR procedure to enable resection of the polyp or lesion. We herein present two hemicolectomy cases performed for a colon cancer showing an exuberant amyloid-like reaction due to ORISE™ Gel. Methods/Case Report At Veterans Affairs Medical Center, two cases of hemicolectomy were performed for colon cancer. Both cases had prior EMR procedure performed for a large cecal polyp. ORISE™ gel was injected with successful lift of the polyp during EMR. Pathology on both cases revealed tubulovillous adenoma with high grade dysplasia; hence right hemicolectomy was performed. Microscopic examination revealed submucosal area with extensive amorphous, eosinophilic/hyaline deposits and surrounding giant cell formation, underlying the cancerous polyp. The deposits were neither refractile nor polarizable. No tattoo pigmentation identified to explain this reaction. The fibrillary eosinophilic deposit raised the concern for concurrent amyloid deposits. This stained pale blue with Masson trichome special stain. Congo red special stain for amyloid was negative and no apple-green birefringence under polarized light was identified. Finally, after extensive ancillary work-up with literature review, the case was signed out as “changes consistent with post-EMR ORISE™ gel artifact”. Results (if a Case Study enter NA) N/A. Conclusion Knowledge of EMR procedure artifact due to use of ORISE™ gel is crucial in routine hemicolectomy specimens performed for unresectable polyps or colon cancer cases. ORISE™ gel creates amorphous hyaline deposits mimicking amyloid. The deposits encompass larger submucosal area with giant cells mimicking foreign body. Delay in turn around time of the case with additional cost for the ancillary work-up. Extensive amyloid-like reaction is a diagnostic pitfall in routine hemicolectomy specimens and, awareness of prior EMR procedure related artifact is important to avoid misinterpretation and delay in patient care.

S2018 Concurrent CMV Colitis and GI Amyloidosis as Initial Presentation of Multiple Myeloma: A Case Report

Introduction: Prior associations with Cytomegalovirus (CMV) colitis and multiple myeloma (MM) or amyloidosis are only described in immunocompromised patients undergoing treatments like transplantation, monoclonal antibodies, or chemotherapy. The concurrent presentation of gastrointestinal (GI) amyloidosis with CMV colitis is rarely reported and should be considered more readily in the hospital. Case Description/Methods: 67-year-old male was admitted to the hospital with bilateral lower extremity deep vein thromboses after transurethral resection of the prostate 8 days prior. He was started on anticoagulation, but due to onset of hematuria, anticoagulation was stopped and an IVC filter was placed. The patient then developed bright red blood per rectum with diarrhea and GI was called. On exam, vitals were stable, and abdomen was non-distended and non-tender. Digital rectal exam showed brown stool. A colonoscopy displayed discontinuous areas of ulcerated, erythematous mucosa with loss of vascular pattern (Figure A). A histologic examination showed terminal ileal mucosa with lymphoid aggregates (Figure B), positive Congo red stain with apple green birefringence and cytomegalovirus inclusions in the colon (Figure C). Subsequent immunology testing demonstrated elevated free lambda light chains with a free kappa to lambda ratio of 0.019. A bone marrow biopsy confirmed lambda restriction and >20% CD138-positive plasma cells, consistent with MM. The patient was started on valganciclovir but showed no improvement of symptoms, which was attributed to his confounding amyloidosis. The patient’s clinical status continued to worsen, and he ultimately expired from cardiac causes. Discussion: It is noteworthy that CMV colitis occurred concurrently with amyloidosis. Immune dysfunction and hypogammaglobinemia in amyloidosis lead to susceptibility to infection, but the inciting organisms usually are H. influenzae, S. pneumoniae, and E. coli. The use of immunosuppressing therapies such as transplantation or chemotherapy increases the likelihood of opportunistic infections. Besides these scenarios, CMV has rarely been reported in patients with amyloidosis or MM. We suggest GI amyloidosis and CMV should be considered and treated rapidly in patients presenting with non-specific GI symptoms. However, our case also highlights the difficulty in measuring effectiveness of antiviral treatment for CMV in GI amyloidosis due to overlap of symptoms between both conditions.Figure 1.: A) skiped areas of ulcerated, friable colon. B) immunohistochemistry CMV viral inclusions, C) Colonic epithelium with amyloidosis.

S2900 Abdominal Lymphadenopathy from AL Amyloidosis Diagnosed via Endoscopic Ultrasound

Introduction: Amyloidosis refers to extracellular tissue deposition of protein fibrils which can affect a variety of organ systems. AL (primary) amyloidosis is a disease caused by the deposition of immunoglobulin light chain fragments and often occurs in the setting of an underlying plasma cell dyscrasia. We describe the diagnosis of AL amyloidosis manifesting as diffuse lymphadenopathy via the use of endoscopic ultrasound (EUS)-guided biopsy. Case Description/Methods: A 66-year-old African American female presented with complaints of fatigue and enlarged cervical lymph nodes. No associated weight loss or night sweats was reported. Past medical history was significant for metabolic syndrome and anxiety. Comprehensive work-up, including flow cytometry and tumor markers, was unremarkable. A contrast enhanced CT scan of the neck, chest, abdomen and pelvis showed mediastinal and peripancreatic lymphadenopathy (largest diameter of 20-mm). An endoscopic ultrasound (EUS) showed few round hypoechoic peri-pancreatic/aortocaval lymph nodes. Fine needle biopsy (FNB) was performed with a 22-gauge needle using a trans-gastric approach. Cytopathologic examination revealed abundant lymphocytes, and cell block showed hyalinized eosinophilic fragments which showed strong Congophilia with focal apple-green birefringence on Congo-red stain consistent with amyloidosis. Liquid chromatography tandem mass spectrometry was performed on peptides extracted from Congo red positive areas of the sample via microdissection and a peptide profile consistent with AL (kappa)-type amyloid deposition was identified. Patient is undergoing workup for an underlying plasma cell dyscrasia and for sites of end organ involvement. (Figure) Discussion: Amyloidosis is a systemic disease which affects many organs, but rarely presents as abdominal lymphadenopathy. EUS-FNB is an important diagnostic modality that allows for tissue diagnosis of Amyloidosis and ruling out malignancy. Our patient presented with diffuse lymphadenopathy, and tissue obtained from a lymph node sampled via EUS-FNB led to the diagnosis of AL amyloidosis.Figure 1.: EUS images demonstrating FNB of an intraabdominal lymph node

S3280 A Rare Case of Isolated ALECT-2 Hepatic Amyloidosis

Introduction: Amyloidosis is a rare disease that is defined by deposition of extracellular fibrils from immunoglobulin light chains which results in organ dysfunction. Many patients with primary systemic amyloid have hepatic involvement. Hepatic amyloid deposition is characterized by mild hepatomegaly and occasional elevated liver enzymes. Ultrasound may reveal a heterogenous echogenicity of the liver and Computed Tomography (CT) may reveal decreased parenchymal attenuation. Biopsy is the gold standard for diagnosis, seen as extracellular amorphous material, and Congo red staining will reveal apple-green birefringence under polarized light. Whereas amyloidosis is most often systemic, there are rare cases of isolated hepatic amyloid deposition. Leukocyte cell-derived chemotaxin 2 (ALECT-2) is a novel amyloid subtype, previously thought to be found in renal amyloid with a predominance in Hispanic patients but has recently been reported in the liver. We present a rare case of isolated hepatic amyloidosis without systemic involvement. Case Description/Methods: A 53-year-old Hispanic female with history of diabetes mellitus, hyperlipidemia, and nonalcoholic fatty liver disease presented to hepatology clinic for liver enzyme elevation. Lab studies were significant for AST 36 U/L, ALT 67 U/L, Alkaline Phosphatase, total bilirubin 2.7 mg/dL, positive anti-smooth muscle antibody (22 U), immunoglobulin G 1049 mg/dL, normal anti-nuclear antibody screen and normal anti-mitochondrial antibody. CT showed post cholecystectomy changes, a calcified granuloma in the right hepatic lobe, but otherwise normal liver. Liver biopsy showed focal amyloid deposition, mild steatosis, mild lobular activity, and rare ballooning hepatocytes without fibrosis. Positron emission tomography-CT, bone marrow biopsy, urine and serum protein electrophoresis were unremarkable. Further amyloid testing showed leukocyte chemotactic factor-2 (ALECT-2) amyloidosis. A referral for second opinion and experimental treatment options was recommended, however the patient declined. The patient has had stable lab values over the last two years with observation. Discussion: This is a rare case of isolated hepatic amyloidosis, highlighting the need for maintaining a broad differential diagnosis in a patient presenting with elevated liver enzymes. Given the rare nature of this condition, it is important to demonstrate this patient’s presentation and two-year outcomes with observation, given lack of available treatment regimens.

Systematic review of accuracy of reporting of Congo red-stained amyloid in 2010–2020 compared with earlier

Background Almost always, Congo red-stained amyloid between polariser and analyser is said to show “green birefringence” or “apple-green birefringence”. In 2010, we found that not all published images showed green, and not all that did showed only green. This systematic review of more recent papers was to find if there had been any improvement in the accuracy of reporting. Materials and Methods MEDLINE was searched on 15 March 2021 for papers published between 2010 and 2020 inclusive mentioning amyloid and Congo red. These were examined for descriptions of colours, which were compared with images. Papers were searched for mentions of anomalous colours, errors in physical optics, and misquotation of references about polarisation. Results In 374 papers, there were 444 descriptions of colours, with 511 images in 257 papers. The commonest descriptions were apple-green, 249/444 (56%), and green, 105/444 (24%). The description agreed with colours seen in 116/511 images (23%) (previously 64/191, 34%). Green was seen in 342/511 images (67%) (previously 159/191, 83%), but not in 169/511 (33%), although each image was reported to show green. Green alone was seen in 103/511 images (20%) (previously 59/191, 31%), and was combined with at least one other colour in 239/511 (47%). Ten papers included the term anomalous. Eight papers incorrectly said that there was green dichroism, three incorrectly used the term green metachromasia, and two incorrectly mentioned green fluorescence. Twenty-seven papers misquoted references. Conclusions There is widespread and increasing inaccuracy of reporting of colours seen in Congo red-stained amyloid. People persist in saying “green birefringence” or “apple-green birefringence”, even when no green is seen, or there are also other colours. Few appear to appreciate that the other colours are genuine, respectable, and helpful, the physical optical principles that explain the colours are now understood, and the best expression to use is anomalous colours. KEY MESSAGE “Green birefringence” and “apple-green birefringence” are inappropriate terms to describe the findings in amyloid stained with Congo red and examined between crossed polariser and analyser, because green is not always seen, and even when it is, other colours are commonly seen as well. The proportions of colour images showing any green and green alone, and the proportion of descriptions that agreed with illustrated colours, significantly decreased in 2010–2020 compared with earlier. The most appropriate and scientific description of the findings is anomalous colours.

Primary amyloidosis of conjunctiva.

A 64-year old male presented in ophthalmology OPD for follow up for refractive errors. He had been wearing bifocal lenses from last 1 year. On local examination, medial canthus of left eye showed a pale yellowish plaque. The rest of the ocular examination and contralateral eye were normal. Slit lamp examination showed a confluent fusiform papule (Figure 1A,B). Computed tomography (CT) scan of the orbit showed no abnormality. Surgical excision was done and tissue sent for histopathological examination showed deposition of a pink homogeneous material in the fibrocollagenous tissue beneath the conjunctival epithelium (Figure 1,C). Congo red stain followed by polarizing microscopy confirmed the pink material to be amyloid with apple green birefringence (Figure 1D,E). Immunohistochemistry (IHC) showed lambda light chain restriction. A diagnosis of conjunctival amyloidosis was made. The patient was then evaluated to rule out systemic amyloidosis or plasma cell dyscrasia. The patient was asymptomatic with no history of trauma, systemic illness, and family history was non-contributory. General and systemic examinations were unremarkable. Complete hemogram, urea, creatinine, liver function test, erythrocyte sedimentation rate, blood glucose, and serum calcium were within normal limits. No abnormality was detected on skeletal survey, electrocardiography, 2D-echocardiography, and ultrasonography of abdomen. Serum protein electrophoresis, serum immunofixation electrophoresis, serum free light chain assay, 24-h urine protein, and urine protein electrophoresis were non-contributory. Bone marrow showed mildly increased plasma cells without light chain restriction on immunohistochemistry. Finally, a diagnosis of primary conjunctival amyloidosis was made and the patient was asked to follow up. Conjunctival amyloidosis occurs secondary to local inflammation and primary form of the disease is very rare. In a previous series published on ocular amyloidosis, only two of 26 ocular cases collected over 30 years had conjunctival involvement. Identification of the disease is a daunting task owing to protean manifestations. Differentiating it from conjunctival inflammation and malignancies is essential. Evaluation for systemic causes is important as the treatment modalities are completely different. While localized form might just need observation or surgical debulking, systemic AL amyloidosis or myeloma would necessitate administration of specific chemotherapy. A long-term follow up is also necessary as recurrence is a known phenomenon and evolution into systemic disease is also a possibility. Concepts design, definition of intellectual content, Literature search, data analysis, manuscript preparation, and manuscript editing: Karuna Jha. Concepts design, definition of intellectual content, manuscript editing: Maitreyee Bhattacharyya. Dr Bhaskar Mitra, Consultant Pathologist, Tribedi and Roy Lab, Kolkata. The authors declare they have no conflicts of interest. The authors received no specific funding for this work. No research on human was performed on this study. Informed consent was taken from the patient. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Unilateral Primary Localised Cutaneous Nodular Amyloidosis of the Nipple

Background: Amyloidosis is characterised by extracellular accumulation of an amorphous fibrillary protein and can affect any organ. It is classified into systemic and localised disease according to its sites of presentation and as primary or secondary according to aetiology. Breast amyloid was first described in 1973 and is extremely rare.Case Presentation: A 61-year-old woman presented in 2020 with a 1-year history of an enlarging tender left nipple with some associated bleeding. Clinical differential diagnoses included a nipple adenoma and an intraductal carcinoma; therefore, a punch biopsy was taken. A full set of screening blood tests were undertaken which were normal, showing no evidence of a plasma cell dyscrasia.The biopsy showed diffuse replacement of the dermis by acellular eosinophilic material showing fracturing. Congo Red stain was positive showing apple-green birefringence under polarised light. A diagnosis of primary localised cutaneous nodular amyloidosis of the nipple was made.Conclusion: We present a rare documented case of isolated primary localised cutaneous nodular amyloidosis of the nipple. This can be considered as a differential diagnosis for patients with a new nipple lesion alongside nipple adenoma and intraductal carcinoma.

Amyloid deposition in granuloma of tuberculosis patients: A single-center pilot study

The formation of granuloma is one of the characteristic features of tuberculosis. Besides, elevated serum amyloid A (SAA) protein level is the indicator for chronic inflammation associated with tuberculosis. The linkage between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid onset and deposition start sites are not well understood in tuberculosis. We hypothesized that granuloma could be a potential site for amyloid deposition because of the presence of SAA protein and proteases, cleaving SAA into aggregation-prone fragments. 150 tuberculosis patients were identified and biopsies were collected from the affected organs. Patients showing eosinophilic hyaline-rich deposits within granuloma and its periphery were further screened for the presence of amyloid deposits. Upon Congo red staining, these hyaline deposits exhibited characteristic apple-green birefringence under polarized light, confirming their amyloid nature in 20 patients. Further upon Immuno-histochemical staining with anti-SAA antibody, the amyloid enriched areas showed positive immunoreactivity. In this pilot study, we have shown granuloma as a potential site for serum amyloid A derived amyloid deposition in tuberculosis patients. This study would expand the clinical and fundamental research for understanding the mechanism of amyloid formation in granuloma underlying tuberculosis and other chronic inflammatory conditions.

CUTANEOUS AMYLOIDOSIS DIAGNOSED BY ORAL MANIFESTATION

Amyloidosis represents a group of rare diseases characterized by extracellular deposition of insoluble amyloid fibrils. A 57-year-old female patient presented with a well-delimited, asymptomatic, submucosal fibrous nodule, measuring 15 mm, localized on the left lower labial mucosa, covered by healthy mucosa, with 2 years of onset. Medical history revealed fibromyalgia. With the clinical hypothesis of mesenchymal or glandular neoplasm, an incisional biopsy was performed. Histopathologic analysis revealed deposition of a hyaline, acellular, eosinophilic, and amorphous material on the connective tissue. Congo red staining was positive, with apple-green birefringence under polarized light, resulting in the diagnosis of amyloidosis. After medical evaluation, no amyloid deposits were found in other tissues and the condition was classified as cutaneous amyloidosis. Surgical excision of the labial lesion was done, with no signs of recurrence after four months. Amyloidosis represents a group of rare diseases characterized by extracellular deposition of insoluble amyloid fibrils. A 57-year-old female patient presented with a well-delimited, asymptomatic, submucosal fibrous nodule, measuring 15 mm, localized on the left lower labial mucosa, covered by healthy mucosa, with 2 years of onset. Medical history revealed fibromyalgia. With the clinical hypothesis of mesenchymal or glandular neoplasm, an incisional biopsy was performed. Histopathologic analysis revealed deposition of a hyaline, acellular, eosinophilic, and amorphous material on the connective tissue. Congo red staining was positive, with apple-green birefringence under polarized light, resulting in the diagnosis of amyloidosis. After medical evaluation, no amyloid deposits were found in other tissues and the condition was classified as cutaneous amyloidosis. Surgical excision of the labial lesion was done, with no signs of recurrence after four months.

AMYLOIDOSIS OF THE TONGUE: A CASE REPORT

Amyloidosis is characterized by the deposition of amyloid fibrils in tissues and organs. This study presents a case of amyloidosis of the tongue. A 65-year-old male patient presented with an irregular and hardened swelling in the lateral tongue, causing significant macroglossia. The patient also demonstrated significant dyspnea and lower extremity edema. Diagnostic hypotheses were malignant tumor and oral manifestation of systemic disease. An incisional biopsy was performed and revealed extracellular deposition of amorphous, eosinophilic, hyaline-like material in the submucosal connective tissue. To confirm the presence of amyloid, staining with Congo red was performed, which showed peach red color on light microscopy and apple green birefringence on polarized light microscopy. The patient was referred to the rheumatology department but died 15 days after diagnosis. Amyloidosis is a rare disease and requires early diagnosis due to the possibility of systemic involvement.

Bilateral yellow plaques on the upper eyelids

Bilateral yellow plaques on the upper eyelids

A rare case of Liraglutide-induced iatrogenic amyloidosis

Abstract Iatrogenic amyloidosis has been linked to injectable drugs such as Enfuvirtide and insulin, which can cause cutaneous deposition of insoluble proteins. We present a rare case in which Liraglutide injections resulted in an iatrogenic amyloidosis. Our patient is a 63 year-old female with a 12-year history of type 2 diabetes mellitus complicated by peripheral neuropathy, on Liraglutide for 10 years, who presented with a 4-month history of developing abdominal subcutaneous masses. She underwent abdominal soft tissue mass excision and biopsy, which revealed Congo red stain positive for amyloid and apple green birefringence on polarization. Lab work and skeletal survey showed no abnormalities. Serum protein electrophoresis revealed no monoclonal protein. Mass spectrometry of amyloid tissue at Mayo clinic revealed Liraglutide detection by immunohistochemistry using glucagon antibodies, dense amyloid deposits typical of amyloid caused by injectable drugs, and a peptide profile inconclusive for an amyloid type-all confirming a diagnosis of iatrogenic amyloidosis caused by Liraglutide injection. This case highlights a very rare side effect of Liraglutide injections. If biopsy confirms amyloid deposits, further workup is absolutely necessary to differentiate the forms of amyloidosis, as the treatment varies based on the kind of amyloidosis. Diabetic patients who are on Liraglutide can have other signs and symptoms which overlap with symptoms of AL amyloidosis. Hence further workup including mass spectroscopy to type the amyloid are vital.

OmpF porins of Enterobacteriaceae possess amyloidogenic properties

Outer membrane porins represent an important group of bacterial virulence associated proteins, whose amyloidogenic properties are actively investigated. Amyloids are protein fibrils with highly ordered beta‐sheet‐rich spatial structure and unique physicochemical properties including unusual resistance to treatment with different detergents and proteases. In prokaryotes, at least ten different functional groups of functional amyloids have been identified. Several outer membrane porins of gram‐negative bacteria were shown to adopt amyloid state. In this study, we analyzed amyloid properties of the OmpF porins of Escherichia coli and Salmonella enteritidis species which are known to be associated with the virulence and pathogenic properties of these bacteria in humans and animals. Our data show that recombinant OmpF proteins form fibrils with morphology typical for amyloids. The in vitro obtained aggregates of OmpF demonstrate resistance to treatment with cold ionic detergents and proteases. Moreover, these aggregates bind amyloid‐specific dye thioflavin T and exhibit apple‐green birefringence in polarized light upon staining with Congo Red dye. Overall, these data confirm the amyloidogenic properties of the OmpF porins of E. coli and S. enteritidis in vitro and suggest that these proteins could represent novel functional bacterial amyloids probably associated with pathogen‐host interactions.

Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment.

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)." Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 73, 35, 15, and 5months. All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine. Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.

Evaluation of multinodular goiter and primary hyperparathyroidism leads to a diagnosis of AL amyloidosis

BackgroundAmyloid goiter, defined as excess amyloid within the thyroid gland in such quantities that it produces a clinically apparent goiter, is a very rare manifestation of systemic amyloidosis with cases commonly seen in the setting of Amyloid A (AA) amyloidosis. Amyloid goiter as the primary clinical manifestation secondary to Amyloid light chain (AL) amyloidosis is very rare. We present a case of AL amyloidosis with initial manifestation as goiter with amyloid deposition in the thyroid and the parathyroid gland.Case PresentationA 73 year old male presented with goiter and compressive symptoms of dysphagia and hoarseness. Laboratory workup revealed normal thyroid function, nephrotic range proteinuria, elevated serum calcium level with an elevated parathyroid hormone level (PTH) consistent with primary hyperparathyroidism. Thyroid ultrasound showed an asymmetric goiter with three dominant nodules. Cervical computed tomography revealed a goiter with substernal extension and deviation of the trachea. Fine needle aspiration was unsatisfactory. There was also evidence of osteoporosis and hypercalciuria with negative Sestamibi scan for parathyroid adenoma. The patient underwent a total thyroidectomy and one gland parathyroidectomy. Pathology revealed benign thyroid parenchyma with diffuse amyloid deposition in the thyroid and parathyroid gland that stained apple green birefringence under polarized light on Congo Red stain. Immunochemical staining detected AL amyloid deposition of the lambda type. Bone marrow biopsy revealed an excess monoclonal lambda light chain of plasma cells consistent with a diagnosis of AL amyloidosis secondary to multiple myeloma affecting the kidney, thyroid, parathyroid gland, and heart. He was treated with 4 cycles of chemotherapy with a decrease in the M spike and light chains with a plan to pursue a bone marrow transplant.ConclusionAmyloid goiter as the primary clinical manifestation secondary to AL amyloidosis with deposition in the thyroid and parathyroid gland is rare. The top differential for amyloid deposits in the thyroid includes systemic amyloidosis or medullary thyroid carcinoma. The definitive diagnosis lies in the histopathology of the thyroid tissue. To diagnose systemic amyloidosis as the etiology for a goiter, a solid understanding of the causes of systemic amyloidosis coupled with a thorough evaluation of the patient’s history and laboratory data is necessary.

Tubuloductal/syringoid variant of central odontogenic fibroma with amyloid?

<h3>Introduction</h3> Glandular tumors of jaw bones present, most often, histopathologic features of salivary gland and, rarely, of cutaneous glandular neoplasms and are thought to predominantly originate from odontogenic epithelium. <h3>Materials and Methods</h3> An unusual maxillary tumor in a 74-year-old male is presented exhibiting radiolucency and root resorption in the apical area of teeth #6-7. <h3>Results</h3> Preparations revealed occasionally branching tubular cords and ductal structures characterized, mostly, by a bilayer composed of luminal Ber-EP4, cytokeratin (CK) 7 and occasionally CK8/18 positive cells and varying from cuboidal to low columnar, and abluminal, CK5/6 positive, basal/basaloid cells revealing nuclear reactivity for p63/p40. Smooth muscle actin and calponin were negative, save for a single focus for calponin, confirming absence of myoepithelial support or epithelial mesenchymal transition. CK19 exhibited staining of both layers, the luminal being more intense. Eosinophilic secretory material and, occasionally, a luminal pellicle were decorated with CK8/18 and polyclonal carcinoembryonic antigen (CEA). CD1a identified only rare Langerhans' cells and Ki67 decorated 1-2% of abluminal cell nuclei. Small solid nests of epithelial cells were also present. Infrequently, an apparent transition of a nest into a tubular structure was appreciated. The partially inflamed stroma featured multiple hyalinized acellular deposits consistent with amyloid, as confirmed by bright orange Congo red reactivity with apple-green birefringence, which reacted with antibodies against odontogenic ameloblast-associated (ODAM) protein but not amelotin and secretory calcium-binding phosphoprotein proline-glutamine rich 1. <h3>Conclusions</h3> Based on the above the diagnosis of tubuloductal/syringoid variant of central odontogenic fibroma with ODAM amyloid is favored.

Localized gastric amyloidosis in a patient diagnosed with Hodgkin lymphoma- A case report and review of literature

Gastrointestinal amyloidosis (GIA), a protein deposition disorder, has numerous etiologies and manifestations and poses a significant diagnostic and treatment challenge. GIA is either acquired or genetic, and it is most commonly caused by chronic inflammatory disorders (AA amyloidosis), hematologic malignancy (AL amyloidosis), and end-stage renal disease (Beta-2 amyloidosis). In AL amyloidosis, the amyloid forming protein is derived from the light chain component of a protein in the blood called monoclonal immunoglobulin. These light chains are produced by abnormal cells (known as plasma or B cells) found in the bone marrow. AL amyloidosis can be caused by abnormal light chains produced by lymphomas or chronic lymphocytic leukaemia(CLL) in rare cases. Hodgkin lymphoma has been found to be associated with systemic amyloidosis and particularly with renal amyloidosis with an incidence of less than 1%.Here we report a rare case of a 61-year old female patient who was previously diagnosed with Hodgkin lymphoma and underwent chemotherapy, now presented with anemia, dypnoea and was found to have a non healing ulcer in the body of the stomach. Histopathological examination revealed gastric amyloidosis which was confirmed with Congo red stain and apple green birefringence under polarized light.

Renal Amyloidosis: Presentation, Diagnosis, and Management

More than 35 amyloid precursor proteins have been identified and many have tropism for the kidney. Renal amyloidosis is most commonly seen in AL and AA amyloidosis and the main clinical manifestations are proteinuria and progressive renal dysfunction. On renal pathology, hallmark findings of amyloidosis include Congo red positivity with apple-green birefringence and randomly arranged fibrils measuring 7-12 nm in diameter on ultrastructural examination. Management of renal amyloidosis typically combines therapy targeting the underlying amyloid process and supportive management. Patients with renal amyloidosis who progress to end-stage renal disease can be treated with dialysis, and in selected patients, with renal transplantation.

Renal Amyloidosis: A Clinicopathological Study From a Tertiary Care Hospital in Pakistan.

IntroductionSystemic amyloidosis can affect any organ in the body, but the kidney is the most commonly involved site. It is characterized by the extracellular deposition of insoluble fibrillar proteins. Amyloid deposits can be identified histologically by Congo red stain, which gives apple-green birefringence under polarized light. Typing of renal amyloidosis is done by direct immunofluorescence on frozen tissue. The most common types of amyloidosis seen in renal tissue are amyloid light chain (AL) primary amyloidosis and amyloid A (AA) secondary amyloidosis. Although primary amyloidosis is considered the most common type in western countries, however, in the subcontinent region, secondary amyloidosis is more common.The spectrum of signs and symptoms in renal amyloidosis is variable including isolated proteinuria, nephrotic syndrome, hypertension, hypotension, and renal insufficiency. The present study aims to evaluate the incidence and aetiology of various types of renal amyloidosis, determine their distribution within the kidney, and study various clinicopathological features.ObjectiveThe present study aims to evaluate the aetiology and clinicopathological profile of renal amyloidosis, determine its various types, and their distribution within the kidney.Materials and methodsThis retrospective cross-sectional study was conducted from 1st January 2013 to 31st December 2020 at the Department of Histopathology, Shifa International Hospital (SIH), Islamabad. All renal biopsies diagnosed as renal amyloidosis were included in the study. Data were analysed using SPSS version 23 (IBM Corp., Armonk, NY). Frequency and percentages were calculated for qualitative variables, and mean and standard deviation were calculated for quantitative variables.ResultsA total of 131 cases were diagnosed with renal amyloidosis during the study period of eight years (from 1st January 2013 to 31st December 2020) at SIH. The age range varied from 17 to 82 years. The mean age of the patients was 45 ± 16.33 years. Out of 131 patients, 82 (62.6%) were males and 49 (37.4%) were females. Amongst them, 72 (54%) cases were diagnosed with secondary AA amyloidosis and 16 (12%) cases were diagnosed with primary AL amyloidosis. The rest of the cases 43 (34%) were of indeterminate type. The associated conditions in secondary amyloidosis were tuberculosis in 41 (57%), rheumatoid arthritis in 16 (22%), ankylosing spondylitis in five (7%), lymphoma in three (4%), diabetes in two (3%), and chronic osteomyelitis, chronic heart disease, hepatitis, and vasculitis in one case each (1.7%). Out of 16 cases reported with AL amyloidosis, 10 cases (62.5%) had a history of multiple myeloma. The most common clinical presentation was nephrotic syndrome followed by subnephrotic proteinuria, renal failure, and hypertension.ConclusionThe findings of the present study show underlying etiological factors and clinicopathological characteristics of renal amyloidosis. AA amyloidosis is the most common type of renal amyloidosis in our study and tuberculosis is the most common aetiological factor. AL amyloidosis is less frequent in our population.