Cytoplasmic PPARγ Significantly Correlates With P53 Immunohistochemical Expression and Tumor Size in Localized Tenosynovial Giant Cell Tumor.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths. It has an inflammatory neoplastic nature, with a clinical presentation ranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized forms of TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient's quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets. METHODS: The study is cross-sectional, in which 27 LTGCT cases were collected from the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed. RESULTS: All the 27 collected LTGCT cases were located in the small joints of patients' hands. Cases with solitary LGTCTs constituted 55.6% (n = 15), while 44.4% (n = 12) had multiple LTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity. CONCLUSION: PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

Xanthogranulomatous pleuritis induced by recurrent biliothorax due to a biliopleural fistula: The first case report in the literature.

Xanthogranulomatous pleuritis is an extremely rare pathological entity, characterized by the infiltration of foamy cells and multinucleated giant cells within the pleural space. This condition often mimics infectious and neoplastic processes, presenting significant diagnostic challenges. This report details the first documented case of xanthogranulomatous pleuritis induced by recurrent biliothorax due to a biliopleural fistula, presenting a unique clinical scenario. We describe the clinical presentation, diagnostic hurdles, and both the surgical and medical management of this case. The discovery of biliothorax, evidenced by pleural fluid bilirubin levels that exceed serum bilirubin levels, underscores the importance of considering biliothorax in the differential diagnosis of recurrent pleural effusions, particularly in patients with a history of trauma. This case emphasizes the need for heightened awareness and a multidisciplinary approach in the diagnosis and treatment to effectively manage this complex condition and prevent recurrence.

Xanthogranulomatous pancreatitis: A rare entity in the spectrum of pancreatic lesions, a case report.

INTRODUCTION: Xanthogranulomatous pancreatitis (XGP) is a rare, benign, and idiopathic disease that often presents with non-specific symptoms and can mimic or coexist with other pancreatic diseases. Despite its infrequency, XGP is frequently misdiagnosed as a pancreatic neoplasm, with only 15 reported cases in the literature. The pathogenesis of XGP remains unclear. CASE REPORT: We present the case of a 34-year-old woman with no pathological history who experienced continuous abdominal pain and oral intolerance, without signs of cholestasis. An abdominal CT scan initially suggested a cystic neoplasm of the pancreas, leading to a laparotomic cephalic duodenopancreatectomy. The anatomopathological study and immunohistochemistry revealed XGP in association with a mucinous cystic neoplasm with mild to moderate atypia. The patient remained hospitalized for six days post-surgery without any complications. DISCUSSION: XGP may be induced by the inflammatory reaction secondary to the obstruction of the pancreatic duct by mucin. The etiology is unknown, but it is attributed to a combination of obstruction, hemorrhage, or ductal infection. Abdominal pain is the most common symptom. Differentiating XGP from malignant processes of the pancreatic gland is challenging. Surgical treatment typically involves the Whipple procedure; however, echoendoscopy with biopsy is now available for a more accurate and early differential diagnosis. CONCLUSION: XGP is a rare and challenging differential diagnosis for pancreatic neoplasms. Due to its potential to mimic malignant lesions, a high index of suspicion is necessary. Echoendoscopy with fine-needle aspiration biopsy should be considered a routine diagnostic tool before major surgery, such as the Whipple procedure.

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19.

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19 + patients.

Single-cell analysis of a progressive Rosai-Dorfman disease affecting the cerebral parenchyma: a case report.

Neurologic Rosai-Dorfman disease (RDD) is a rare type of non-Langerhans cell histiocytosis that affects the central nervous system. Most neurologic RDDs grow like meningiomas, have clear boundaries, and can be completely resected. However, a few RDDs are invasive and aggressive, and no effective treatment options are available because the molecular mechanisms involved remain unknown. Here, we report a case of deadly and glucocorticoid-resistant neurologic RDD and explore its possible pathogenic mechanisms via single-cell RNA sequencing. First, we identified two distinct but evolutionarily related histiocyte subpopulations (the C1Q+ and SPP1+ histiocytes) that accumulated in the biopsy sample. The expression of genes in the KRAS signaling pathway was upregulated, indicating gain-of-function of KRAS mutations. The C1Q+ and SPP1+ histiocytes were highly differentiated and arrested in the G1 phase, excluding the idea that RDD is a lympho-histio-proliferative disorder. Second, although C1Q+ histiocytes were the primary RDD cell type, SPP1+ histiocytes highly expressed several severe inflammation-related and invasive factors, such as WNT5A, IL-6, and MMP12, suggesting that SPP1+ histiocytes plays a central role in driving the progression of this disease. Third, oligodendrocytes were found to be the prominent cell type that initiates RDD via MIF and may resist glucocorticoid treatment via the MDK and PTN signaling pathways. In summary, in this case, we report a rare presentation of neurologic RDD and provided new insight into the pathogenic mechanisms of progressive neurologic RDD. This study will also offer evidence for developing precision therapies targeting this complex disease.

Supranuclear Palsy as an Initial Presentation of the Adult-Onset Niemann-Pick Type C.

(1) Background: Niemann-Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal-lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The adult form presents in patients greater than 15 years of age but is rarely seen after the age of 30. Common symptoms of the late adult-onset category of NP-C1 include progressive cognitive impairment and ataxia, with psychiatric and movement disorders presenting less frequently than in other forms of NP-C1. Dystonic movement disorders present most frequently, along with chorea, myoclonus, and parkinsonism. Herein, we present a rare case of NP-C1, diagnosed at age 35 with an initial symptom of supranuclear palsy. The goal of the presented case is to highlight the importance of the neurological examination and an inclusive differential diagnosis in patients with new-onset supranuclear palsy. (2) Methods: A single case report. (3) Results: A 46-year-old male with a past medical history of NP-C1 was admitted to the hospital for respiratory distress. He was noted to have a supranuclear gaze palsy with partially preserved voluntary saccades to the right. His mother revealed that he first had difficulty moving his eyes at the age of 34. After multiple consultations and genetic testing one year later, he was diagnosed with NP-C1. (4) Conclusions: Because NP-C1 affects many regions of the brain responsible for eye movements, neurological eye assessments can be a useful tool in diagnoses. Furthermore, eye movement abnormalities may be the initial presenting symptom of NP-C1, predisposing patients to misdiagnosis with progressive supranuclear palsy and other conditions that may mimic early-stage NP-C1. Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past. The NP-C Suspicion Index was developed to assist in diagnoses, but its efficacy is unclear with late adult-onset NP-C1. Although no cure exists, early identification can facilitate an improved symptom management course for patients. Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1. Delays between symptom onset and treatment initiation are likely to result in poorer outcomes and a progression of neurological symptoms. High doses may present tolerance concerns, especially in cases of delayed treatment and advanced neurological deficit.

Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy.

Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.

Clinicopathological study of ophthalmic cutaneous and mucocutaneous non-langerhans cell histiocytic lesions.

BACKGROUND: The "C group" of the histiocytic disorders is characterized by non-Langerhans-cell histiocytic lesions in the skin, mucosal surfaces, or both, out of which Juvenile xanthogranuloma (JXG) is the most common typically affecting the skin. The eye is the most common extra-cutaneous site of JXG., we aim at providing our clinical and histopathological experience with this group of diseases including the adult-onset xanthogranuloma (AXG). METHODS: This is a retrospective cohort study of all patients with the tissue diagnosis of ocular and periocular cutaneous and mucocutaneous non-LCH disorders who presented to us over a period of 25 years (January 1993 to December 2018). RESULTS: Twenty patients were diagnosed as "Group C" disease with an age range of 2 months-60.9 years. Eleven patients were females (55%) and nine were males (45%). The involvement was mostly unilateral in 80.9%. All cases fell into the xanthogranuloma family with 11 JXG patients, 8 AXG patients of skin and ocular surface, and one patient with solitary reticulohistiocytoma (SRH). The clinical site of involvement in JXG was primarily in the eyelid in 5 patients (45%), ocular surface lesions in 2 (18%), iris in 2 (18%), choroidal and bilateral orbital lesions in 1 patient each (9%). The group of AXG, presented equally with eyelid lesions in 4/8 and ocular surface lesions in 4/8. The non-Langerhans' histiocytic infiltrate showed supportive immunohistochemical staining properties (reactive to CD68 marker and negative to S-100 and langerin markers). CONCLUSION: Among the rare histiocytic disorders, xanthogranulomatosis is the commonest and has wide clinical manifestations. Accurate diagnosis needs to be supported by typical histopathological findings. JXG was the commonest in our study with relatively older mean age at presentation and frequent eyelid rather than iris involvement. AXG is often confused with xanthelasma when involving the eyelids with corneal limbal involvement is relatively frequent.

Extranodal Rosai-Dorfman Disease: a rare presentation involving anterior chest wall in a middle-aged female.

Rosai-Dorfman Disease is a rare benign disorder involving overproduction of immune cells, causing swollen lymph nodes and, in rare cases, the sternum. The sternal involvement may cause chest pain and masses. Diagnosis is confirmed through clinical examination, biopsy, and imaging. Treatment options may include surgery, radiation, or steroids. In this case study, we present an unusual example of extranodal Rosai-Dorfman Disease involving the sternum, bilateral clavicles and first three ribs, and pectoral muscle with no associated lymphadenopathy or systemic symptoms in a 57-year-old female. The etiology, pathology, immunohistochemistry, imaging findings, and treatment options of this unique disease are discussed.

Facial Cutaneous Rosai-Dorfman Disease: Dermoscopic Findings with Successful Surgical Treatment.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by an accumulation of activated histiocytes within the affected tissues. It is a heterogeneous disease that includes the classical (nodal) and extra-nodal variants. The cutaneous form of the disease without the characteristic lymphadenopathy is rare and is often misdiagnosed as other dermatologic diseases. Misdiagnosis as lymphoproliferative and infectious diseases such as lymphoma and tuberculosis have been reported in the literature. Herein, we report a case of facial cutaneous RDD with successful surgical treatment. In addition, we provide dermoscopic findings and literature review as dermoscopy can be a useful adjuvant tool in the diagnosis of cutaneous RDD.

Xanthogranulomatous inflammation of the lower jaw bone: a rare case report.

Xanthogranulomatous inflammation (XGI) is an uncommon type of chronic inflammation and is histologically characterized by foamy histiocytes and giant cells. The most common sites of occurrence are kidneys and gallbladder. The etiology remains controversial. Involvement of the lower jaw bone is rare. In this study, we report a case of XGI presenting in the lower jaw.

Xanthogranulomatous Endometritis with calculus formation in setting of prolapsed uterus.

Xanthogranulomatous inflammation is a rare benign inflammatory lesion characterized by sheets of lipid-laden foamy histiocytes. It has been reported in various organs, mainly the kidney and gall bladder. Xanthogranulomatous endometritis (XGE) is sporadic, with only a few cases reported in the English medical literature. Herein, we report a case of xanthogranulomatous endometritis with the formation of stones in a 50-year-old female patient with a prolapsed uterus. Grossly the endometrium was irregular, and the uterine cavity was filled with a yellow friable material, a polypoid growth, and yellowish stones. The microscopy showed sheets of histiocytes with few preserved endometrial glands. In this case, the xanthogranulomatous inflammation may mimic a clear cell carcinoma involving the endometrium and myometrium. One of the important differential diagnoses is malakoplakia. Immunohistochemistry and special stains are helpful in diagnosis.

Xanthogranulomatous Change in a Leiomyoma: First Report of an Extremely Rare Variant/Degenerative Change.

Xanthogranulomatous inflammation, a specific form of chronic inflammation, is marked by parenchymal destruction, proliferative fibrosis, and infiltration of typical foamy histiocytes admixed with hemosiderin-laden macrophages and foreign-body giant cells. Myometrial xanthomatosis, a term designated for nodular or diffuse histiocytic hyperplasia of the myometrium, has been reported in association with pregnancy-related procedures. Moreover, a 2-3-fold increase in histiocytic counts has been observed in leiomyomatous areas than in adjacent normal myometrium. The first evidence of collections of lipid-laden macrophages was documented in the form of yellowish degeneration of uterine leiomyomas. We report a case of xanthogranulomatous change in a leiomyoma in a 47-year-old female who presented with abnormal uterine bleeding. To the best of our knowledge, this is the first report of xanthogranulomatous variant/degenerative change in a leiomyoma. This case highlights a new variant of leiomyoma which both gynecologists and pathologists should be aware of as it may pose a diagnostic challenge both clinically as well as pathologically.

Bilateral primary orbital xanthogranulomas: A case report and comparison of xanthomatous conditions.

This report describes an unusual and diagnostically challenging case of subcutaneous soft tissue xanthogranulomas of bilateral orbits of a 58-year-old female patient seen in a private oculoplastics practice. Accurate and timely diagnosis is crucial in xanthogranulomatous diseases so that any systemic manifestations can be identified and addressed in a multidisciplinary fashion. Periorbital xanthogranuloma is a frequent early manifestation of adult xanthogranulomatous disease, and its association with life-threatening systemic disease requires accurate diagnosis and prompt work-up. This case describes an otherwise asymptomatic patient who presented with bilateral orbital masses causing visually significant ptosis, initially diagnosed as soft tissue xanthomas, and later identified as xanthogranulomas. It is important for physicians of all fields, from primary care to surgical subspecialty, to be aware that xanthogranulomatous disease may first present as periorbital lesions and/or orbital masses, and that further work-up for vision and life-threatening systemic disease is warranted.

Xanthogranulomatous Oophoritis: A Rare Case Report.

Xanthogranulomatous oophoritis is a rare, chronic and non-neoplastic condition in which a heavy foamy histiocyte inflammatory infiltrate admixed with neutrophils, plasma cells, multinucleated giant cells, fibroblasts and foci of necrosis causing extensive tissue damage and organ destruction. The gallbladder and kidney are just two examples of the different organs that exhibit histological changes resembling xanthogranulomatous alteration. The present case involved a 40-year-old female who presented with a tuboovarian mass and was ultimately diagnosed with xanthogranulomatous oophritis, despite initial clinicoradiological suspicions for malignancy. Xanthogranulomatous oophritis is a significant entity because, clinically and radiographically, it resembles tumours of the ovary and hinges on a careful histopathological analysis to establish a diagnosis.

Signet-ring cell sinus histiocytosis: report of the clinicopathologic characteristics of 4 cases with emphasis on the differential diagnosis of signet-ring cell lesions.

Signet-ring cell sinus histiocytosis (SRCSH) represents a distinctly rare reactive phenomenon predominantly affecting axillary and pelvic lymph nodes (LNs) of individuals with breast or prostatic adenocarcinoma. Reports of SRCSH in the literature are sparse with only 12 previous examples, thus underscoring the rarity of this process. Here, we report 4 additional SRCSH cases affecting 2 women and 2 men (M/F = 1:1; age range: 50-71 years; mean age = 61 years). In the 2 men, pelvic LNs were excised during radical cystoprostatectomy for genitourinary cancer, whereas in one woman, SRCSH was incidentally discovered in axillary LNs during mastectomy for breast adenocarcinoma. The other female patient presented with a history of aortic valve replacement and enlarged supraclavicular LNs. Microscopically, all involved LNs exhibited marked distention with filling of the subcapsular and medullary sinuses by sheets of signet-ring histiocytes containing a singular large, cytoplasmic vacuole and a crescentic nucleus. Overt cytologic atypia, pleomorphism, and mitoses were absent. Erythrophagocytosis and occasional fibrosis were appreciated. None of the LNs with SRCSH showed evidence of metastatic tumor. Immunohistochemically, signet-ring sinus histiocytes were invariably positive for CD68 and CD163 but were negative for pancytokeratins. The histopathologic characteristics of SRCSH, albeit bland, in conjunction with the patient's medical history, may be misinterpreted as metastatic adenocarcinoma with signet-ring cell configuration. Immunohistochemical confirmation of the histiocytic lineage of the lesional cells in SRCSH usually suffices for rendering an accurate diagnosis. The underlying pathogenetic mechanism and possible biologic significance of SRCSH remain currently unknown.

Systemic histiocytic disorder in a jaguar (Panthera onca).

A 7-year-old captive female jaguar (Panthera onca) was presented with a 7-day history of dyspnoea and weight loss. Clinical examination revealed hepatomegaly and elevated serum alanine aminotransferase activity. Pulmonary ultrasonography revealed comet-tail images and an alveolar pattern was detected on thoracic radiography. Due to the poor prognosis, the jaguar was euthanized after 10 days. At necropsy, the main gross findings were hepatomegaly, splenomegaly and multifocal to coalescent, slightly elevated grey areas in the lungs. Histological examination revealed neoplastic proliferation of pleomorphic histiocytes arranged in cohesive sheets in the lungs, liver, spleen, kidneys and lymph nodes. Neoplastic cells had intense immunolabelling for vimentin and ionized calcium-binding adaptor molecule 1, and were immunonegative for pancytokeratin, E-cadherin, CD20, CD3 and CD79α. These findings were compatible with a systemic histiocytic disorder, distinct from any well-defined histiocytic proliferative disease in domestic animals.

Sinonasal and ear manifestations of Erdheim-Chester disease.

To calculate the prevalence of sinonasal and ear involvement in an Erdheim-Chester disease (ECD) population, to describe the different ear, nose and throat (ENT) manifestations and to study the association between ENT involvement, other organ involvement, and BRAF mutations. We led a retrospective monocentric study in the national referral center for ECD. One hundred and sixty-two patients with ECD and ENT data were included between January 1, 1980 and December 31, 2020. Ear and nose clinical and radiological findings were noted. We described and studied the prevalence of ENT involvement in ECD population. The association between sinonasal and ear involvement, other organ involvement, and BRAF mutations was calculated. The prevalence of ENT manifestations is around 45%. No clinical rhinologic or otologic signs were specific to ECD. Sinus imaging was abnormal in 70% of cases. A bilateral maxillary sinus frame osteosclerosis was highly specific of ECD. Associations were found between the sinus MRI imaging type and BRAF status, central nervous system involvement, cerebellum involvement and xanthelasma. Sinonasal or ear involvement is frequent in ECD and has specific imaging features for sinuses. Trial registration: #2011-A00447-34.

Erdheim-Chester Disease Involving the Biliary System and Mimicking Immunoglobulin G4-Related Disease: A Case Report.

First described in 1930 as a lipoid granulomatosis, Erdheim-Chester disease (ECD) is a rare histiocytosis encompassing a group of disorders caused by overproduction of histiocytes, a subtype of white blood cells. This disease most commonly involves the bones and can affect organs in the abdomen; however, biliary involvement is rarely reported. We report a case of ECD with biliary involvement, which rendered it difficult to radiologically distinguish ECD from immunoglobulin G4-related disease.

Malakoplakia of the Gallbladder: A Case Report.

Histiocytes are cells that are involved in the immune responses of the body. They are unable to properly break down the bacterial material in malakoplakia, a chronic granulomatous histiocytic disease that occurs in immunocompromised patients and autoimmune conditions. Very few reports of these lesions exist, as those that occur in the gallbladder. It typically affects the urinary bladder, alimentary tract, cutaneous, hepato-biliary, and male and female genital systems. These lesions are usually incidental findings that result in patients being misdiagnosed. A 70-year-old female presented with right lower quadrant abdominal pain, and malakoplakia of the gallbladder was diagnosed. Histopathology findings revealed malakoplakia of the gallbladder, and the same was confirmed with special stains such as periodic acid-Schiff (PAS). This case highlights the role of gross and histopathology findings as a clue to the diagnosis, which helps the surgeon with further management.