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We present an unusual case of liver involvement in monoclonal gammopathy with generalized crystal-storing histiocytosis (G-CSH). A bone marrow storage disease was diagnosed in a 79-year-old man with monoclonal gammopathy of uncertain significance (MGUS). The patient presented with pleural effusion, an osteolytic lesion of the humerus, and an increase of aspartate transaminase and cholestatic markers that raised the clinical suspect of liver disease. A second bone marrow biopsy confirmed the diagnosis of MGUS with a histiocytic component suggestive for G-CSH. Liver biopsy showed an unremarkable histology, no significant inflammatory infiltrates, and intrasinusoidal foamy histiocytes. PAS and Masson’s trichrome stains, showed, in the cytoplasm of both histiocytes and hepatocytes, rod-shaped eosinophilic crystals, which were immunoreactive for kappa light chains. Transmission electron microscopy performed on reprocessed histological sections confirmed the presence of crystals in the hepatocyte cytoplasms. Immunogold labeling intensely stained crystals for kappa light chains. To the best of our knowledge, this is the second case in which an intrahepatocellular crystal storage is described during liver involvement in G-CSH. The present case also suggests that an increase in liver serum enzymes may support the clinical diagnosis of liver CSH in a patient with MGUS.

The renal diseases commonly associated with myeloma include primary amyloidosis, cast nephropathy, and light chain deposition disease. Less frequent forms of renal involvement encountered in the course of myeloma are crystalline and non-crystalline proximal tubulopathies, neoplastic plasma cell infiltration, and immunoglobulin crystallization in interstitial histiocytes and glomerular cells including podocytes. Light chain proximal tubulopathy (LCPT) caused by aggregation of non-crystalline and rarely crystalline deposits of monoclonal light chains in the cytoplasm of proximal tubular epithelial cells, accounts for less than 5% of monoclonal gammopathy-associated kidney diseases. We report the case of a 48-year-old Indian woman with multiple myeloma, who presented with acute kidney injury and nephrotic syndrome, in whom the renal biopsy revealed widespread crystalline inclusions in extraglomerular and glomerular compartments. We present illustrative light microscopic (LM) and diagnostic electron microscopic (EM) findings of this case which enabled a diagnosis of crystalline LCPT, crystal storing histiocytosis, and crystalline podocytopathy occurring synchronously with myeloma cast nephropathy. While documenting this unique juxtapositioning of multicompartmental paraproteinemic renal injury in multiple myeloma, diagnosed after EM analysis of the patient's renal biopsy, we discuss the pathogenetic pathways of this condition along with the clinical implications. Due to intrinsic structural properties of the crystals, they frequently escape detection by routine LM, necessitating EM analysis for their diagnosis. Given the prognostic implications of tubulopathies complicating myeloma, LCPT is a critically important diagnosis, highlighting the need for a comprehensive renal biopsy evaluation inclusive of EM for the practice of precision medicine in such scenarios.

The authors report the clinicopathological features of crystal-storing histiocytosis (CSH) that involved the orbit and conjunctiva and review published cases of CSH. Cases of histologically proven CSH were identified from archives at the Institute of Ophthalmology, London, and a retrospective review of clinical details and pathology was performed for cases between 1997 and 2017. Four cases of CSH were identified: 1 might have arisen from an inflammatory reaction to a silicone retinal buckle and 3 others occurred with localized B-cell lymphomas. Two patients presented with a conjunctival mass, and 2 had an orbital mass causing proptosis and hypoglobus. One case was associated with amyloid deposition and another had an earlier diagnosis of IgG4-related disease. In the patient without underlying lymphoma, the condition settled with removal of the explant and orbital mass, and the 3 with lymphoma underwent orbital radiotherapy with cessation of disease progression. All patients retained good vision. Ocular CSH is rare, can present in several ways, and should prompt investigation for an underlying lymphoproliferative disorder.

Crystal-storing histiocytosis (CSH) is a rare phenomenon in which crystalline material accumulates in the cytoplasm of histiocytes. Localized gastric CSH is an extremely rare condition. We report a case of localized gastric CSH in a 72-year-old female who presented with diffuse granular mucosa in the gastric fundus and body endoscopically. Biopsy specimens from the stomach showed accumulation of crystal-storing histiocytes, and the crystalline material was immunohistochemically positive for kappa light chains and polyclonal heavy chains. There were no crystal-storing histiocytes in other organs. For the past 5 years, the gastric CSH lesion has remained without any change, and no neoplastic or lymphoproliferative disease has developed. Once the diagnosis of CSH is established, it is necessary to check for an underlying lymphoplasmacytic disorder. However, some cases of localized gastric CSH are not associated with lymphoplasmacytic neoplasia, and these tend to have a good prognosis. Keywords: Crystal-storing histiocytosis, Stomach, Immunohistochemistry, Ultrastructure

Crystal-storing histiocytosis (CSH) is an uncommon histiocytic proliferation reported to involve diverse organs and tissues, but involvement of the central nervous system (CNS) is rare. In most cases CSH is identified in association with underlying lymphoproliferative, plasma cell diseases or rarely with various inflammatory or infectious conditions. CSH is characterized by the cytoplasmic accumulation of crystalline material in histiocytes, most commonly of kappa immunoglobulin light chain. We report a unique case of localized CSH involving the left cerebellum and caudal brain stem in a young man with a history of gout but without known lymphoproliferative or plasma cell disorders. Awareness of this entity is important diagnostically, but also to ensure appropriate management and follow-up, particularly in the absence of apparent underlying malignancy.

Objectives We report the clinicopathologic characteristics of eight cases of crystal-storing histiocytosis (CSH) with bone marrow (BM) involvement (BM-CSH) and review CSH cases published in the English literature. Methods We queried our pathology database for BM cases with CSH mentioned in the final diagnosis/comments from June 2011 to August 2016. Results Eight cases of BM-CSH were identified. The underlying diagnoses consisted predominantly of plasma cell disorders (88%) associated with monotypic κ light chain. In BM aspirates, crystals within histiocytes exhibited a morphologic spectrum including brightly eosinophilic, needle-like, or globule-like. In BM core biopsies, the histiocytes were often in aggregates with intracellular needle-like and/or globular, refractile inclusions. Conclusions BM-CSH is a rare phenomenon and exhibits a heterogeneous crystalline and histiocytic appearance warranting accurate recognition to avoid misinterpretation of a granulomatous condition or storage disorder. In addition, prompt assessment for an underlying B-cell lymphoma or clonal plasmacytic neoplasm is indicated.

Rationale: Crystal sorting histiocytosis (CSH) is a rare disorder that is morphologically characterized by the accumulation of monoclonal immunoglobulin crystals, predominantly of a kappa light chain type, within lysosomes of macrophages. CSH may result in a variety of clinical manifestations depending on the involved organs. In this case report, we aim to describe a patient with ophthalmic manifestations which lead to the diagnosis of multiple myeloma with crystal-storing histiocytosis, crystalline podocytopathy, and light chain proximal tubulopathy. Patient concerns: A 60-year-old male patient presented with progressive bilateral decreased vision for 2 years. Diagnosis: Ophthalmic explorations showed bilateral macular and papillary edema, and multiple crystalline deposits in the anterior stromal cornea and in the retina. Laboratory tests showed nephrotic syndrome and renal dysfunction. Further work-up revealed IgG kappa multiple myeloma, with biopsy-proven combined crystalline podocytopathy and tubulopathy. Interventions: The patient received chemotherapy (bortezomib, cyclophosphamide, and dexamethasone for 3 cycles, then bortezomib, lenalidomide, and dexamethasone). Outcomes: Despite partial hematologic response and improvement of the papilledema and macular edema, the patient developed dialysis-dependent end-stage renal failure. Lessons: This report, highlighting the protean presentation of paraprotein-mediated injuries, provides additional information on the ocular anomalies not previously described that may be associated with crystal-storing histiocytosis.

This chapter briefly describes reactive or neoplastic mimics of primary cutaneous mesenchymal neoplasms that are commonly encountered by dermatopathologists and can lead to misinterpretation as a primary soft tissue tumor, especially sarcoma. A comprehensive review of these lesions is beyond the scope of this chapter; rather, we focus our discussion on helpful histologic clues, diagnostic pitfalls, and useful ancillary tests. The entities reviewed in this chapter and their clinically important mesenchymal tumor mimics are listed in Table 3.1.

Background Crystal storing histiocytosis (CSH) is a rare disorder characterized by accumulation of histiocytes containing crystalline material inclusions. This entity can be misdiagnosed as infection or tumor. We present a case of idiopathic CSH mimicking metastatic squamous cell carcinoma in a cervical lymph node and review of literature regarding this rare entity. Methods and Results The patient was a 70-year-old man with a medical history of squamous cell carcinoma of the right base of the tongue. The patient presented with an enlarged cervical lymph node, which was clinically diagnosed as metastatic carcinoma. At intraoperative consultation, it was unexpectedly discovered that the lymph node exhibited extensive histiocytosis containing crystal materials. Final pathology identified “crystal storing histiocytosis” because of amyloidal depositions. No metastatic carcinoma was seen. Conclusion After 10 months of follow-up, the patient is disease free. To the best of our knowledge, this unusual clinical presentation is the first to describe CSH mimicking a metastatic carcinoma. © 2015 Wiley Periodicals, Inc. Head Neck 38: E95–E98, 2016

[Figure][1] A 27-year-old woman presented with a thymic mass containing cystic spaces and an atypical lymphoid infiltrate with plasma-cell differentiation. Juxtaposed to the lymphoid component were numerous histiocytes with abundant cytoplasm filled with crystalline and/or globular

Two cases are described of crystal storing histiocytosis (CSH) associated with extranodal marginal zone lymphoma, presenting as lung and subcutaneous masses respectively. Fine-needle aspiration of subcutis and smears prepared from the resected lung masses showed negative images. Cytology slides of both cases were reviewed to identify cytomorphological features for the differential diagnosis between immunoglobulin crystals and mycobacteria. The crystals in CSH consist of straight and needle shaped rods with pointed or angular edges and are more variable in thickness than the uniformly thin mycobacteria. Mycobacteria show a haphazard distribution, whereas crystals are frequently present in parallel arrays. Small lymphoid or plasma cells are identified in the background of CSH, whereas a necrotic and inflammatory background is seen in mycobacteriosis. Additional samples for culture in the case of mycobacteriosis, or flow cytometry and molecular clonality testing in the case of CSH can provide critical data for a definitive diagnosis.

[Figure][1] A 62-year-old woman was found to have a breast mass on screening mammography. A core biopsy was performed and revealed heterogeneous aggregates of lymphocytes and plasma cells juxtaposed against sheets of histiocytes with punctate areas of necrosis mimicking necrotizing

Crystal-storing histiocytosis (CSH) is a rare disorder associated with crystalline immunoglobulin deposition in the cytoplasm of histiocytes and is usually associated with lymphoproliferative or plasma cell disorders (LP-PCD) that express monoclonal immunoglobulin. Localized CSH without underlying LP-PCD are extremely rare. We report a case of localized CSH in breast which was an unexpected difficult diagnosis. The awareness of this entity is of importance to delineate it morphologically from other common differential diagnosis and enable appropriate management. To date, this is the first case of localized CSH reported in breast in a patient with no known history of LP-PCD.

Sir,Crystal storing histiocytosis (CSH) is a rare phenomenon characterised by cytoplasmic accumulation of crystalline material in macrophages. Less than 100 cases of CSH have been reported so far. ...

Crystalloid inclusions are rarely en-countered within the central nervous system (CNS). Aside from the more common Hirano bodies and Rosenthal fibers, which occur within neurons and astrocytic processes, both being composed of cytoskeletal proteins, eo-sinophilic crystalloid inclusions have been recently described within oligodendrocytes in a case of adult-onset, complicated form of hereditary spastic paraplegia [1]. However, crystalloid inclusions may also accumulate within macrophages referred to as crystal storing histiocytosis (CSH). CSH is a rare condition, which most often occurs within the setting of lymphoproliferative disor-ders, in which immunoglobulins aggregate within the cytoplasm of macrophages [2]. Localized and generalized forms of CSH are distinguished based on the extent of organ involvement [3]. While the lymphoreticular system, bone marrow, kidney, and lung are most often affected, CNS presentation is ex-tremely rare with 5 cases reported in the lit-erature, so far [2, 3, 4, 5, 6, 7].Herein, we add another case of a 56-year-old male patient, who presented with an intra-cerebral tumor-like lesion. After a first stereotactic biopsy, which displayed only reactive changes including some unspecific infiltration by macrophages, more extensive

We report a rare case of crystal-storing histiocytosis (CSH) associated with marginal-zone lymphoma. A 91-year-old woman with a history of breast cancer presented with masses of the posterior neck, right breast, and left upper arm. An enlarging mass of the neck was removed and was histologically diagnosed as CSH, associated with marginal-zone lymphoma. Masses in the breast and upper arm were evaluated by needle biopsy and revealed as CSH. CSH is a rare condition characterized by the intrahistiocytic accumulation of crystallized immunoglobulins, and is associated with disorders in which monoclonal immunoglobulins are expressed. To the best of our knowledge, there are few previous descriptions of CSH which include the imaging features of this disease. In the present case, the masses showed hypoechogenicity with internal patchy hyperechoic areas on ultrasonography, and an iso-signal to slight hyperintensity compared with muscle on T2-weighted magnetic resonance imaging. We report the imaging findings in CSH and discuss their diagnostic implications.

SUMMARY A case ofmassive crystal-storing histiocytosis with extensive involvement ofthe subcutaneus adipose tissue in a 61-year-old caucasian woman with a lymphoplasmacytic lymphoma (immunocytoma) in transformation to a large cell lymphoma is presented. Paraffin-section immunohistochemistry demonstrated a monoclonal IgM/ kappa immunphenotype of the lymphoma cells and revealed IgM/kappa and, to a lesser extent, IgG/lambda in the crystal-containing histiocytes. Ultrastructurally, the electron dense intracytoplasmic crystals had variable shapes, were occasionally membrane-bound and measured up to 6 μm. The findings are briefly discussed.

SUMMARY: CSH is a very uncommon lesion and is distinctly unusual in the brain. We report a case of CSH within the brain parenchyma in a 27-year-old woman with Crohn disease. Advanced radiologic imaging and anatomic pathology correlation allow this report to serve as a reference for future similar cases.

[Figure][1] Crystal-storing histiocytosis is characterized by intra-cytoplasmic accumulation of crystallized immunoglobulins in histiocytes and is typically associated with disorders that express monoclonal immunoglobulins. A 43-year-old woman with stage IV chronic kidney disease due to

Background Crystal storing histiocytosis (CSH) is a disorder characterized by local or diffuse infiltration of histiocytes containing crystalline inclusions most commonly of immunoglobulin light chain. Involvement of the central nervous system is extremely rare. CSH may be misdiagnosed as an infection or tumor. In patients with involvement of other organs, it is frequently associated with lymphoplasmacytic diseases. Case description A 20-year-old female was evaluated for 2 weeks of progressively worsening headaches. At presentation, she had no history of fevers but reported a sore throat without cough 3-4 days prior. Her past medical history was unremarkable. She denied intravenous drug use or sexually transmitted diseases but lived with an individual with a history of fungal meningitis. On examination she was afebrile, alert, and oriented with a blood pressure of 110/70 mmHg. She had no adenopathy or neurological deficits. Her white blood cell count was minimally elevated. Magnetic resonance imaging revealed a 3.5 × 1.3 × 1.9 cm contrast enhancing lesion of the left temporal lobe with a mild midline shift. Evaluation by multiple specialists suggested a differential diagnosis of an infectious or neoplastic process. Cultures for infectious agents were negative. The biopsy showed CSH. Postoperatively and at 1 month follow up, she was neurologically intact. Conclusion Radiographically and intraoperatively, CSH may mimic an infectious process or neoplasm. Its recognition is critical to facilitate appropriate therapy and prompt screening for an occult lymphoplasmacytic neoplasm, plasma cell dyscrasia or other underlying disease.

Crystal-storing histiocytosis (CSH) is a rare manifestation of a B-cell lymphoproliferative process characterized by intrahistiocytic accumulation of crystallized immunoglobulin involving multiple body sites. We report a case of localized CSH with marginal zone lymphoma (MZL) involving a retroperitoneal lymph node at the left renal hilum. The patient was a 77-year-old man who had hematuria in 2008. On ultrasonography, nephrolithiasis …