Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 7038
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2023  |  Volume : 66  |  Issue : 3  |  Page : 655-658
Crystal storing histiocytosis forming a mass lesion in temporal lobe

1 Department of Medical Pathology, Uludag University Faculty of Medicine, Bursa, Turkey
2 Department of Neurosurgery, Uludag University Faculty of Medicine, Bursa, Turkey
3 Department of Radiology, Uludag University Faculty of Medicine, Bursa, Turkey

Click here for correspondence address and email

Date of Submission13-Apr-2021
Date of Decision08-Jun-2021
Date of Acceptance18-Dec-2021
Date of Web Publication06-Jun-2022


Crystal storing histiocytosis is a disorder characterized by local or diffuse infiltration of histiocytes containing crystalline inclusions. This entity has been reported in several organs, however the involvement of the central nervous system (CNS) is extremely rare and to date only 7 cases of crystal storing histiocytosis (CSH) of CNS have been reported in the English literature. More than 90% patients with CSH had an underlying lymphoproliferative or plasma cell disorders, especially multiple myeloma, lymphoplasmacytic lymphoma or monoclonal gammopathy. Radiologically and intraoperatively, CSH may mimic an infectious process or neoplasm, hence its histopathological confirmation is important to facilitate appropriate treatment. In this report, we describe an additional case of crystal storing histiocytosis in a 48 year old female who presented with a mass lesion in the right temporal lobe of the cerebrum.

Keywords: Central nervous system, crystal-storing histiocytosis, lymphoma, multiple myeloma

How to cite this article:
Özşen M, Tolunay &, Kocaeli H, Parlak M. Crystal storing histiocytosis forming a mass lesion in temporal lobe. Indian J Pathol Microbiol 2023;66:655-8

How to cite this URL:
Özşen M, Tolunay &, Kocaeli H, Parlak M. Crystal storing histiocytosis forming a mass lesion in temporal lobe. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Sep 27];66:655-8. Available from:

   Introduction Top

Crystal storing histiocytosis (CSH) is a non-neoplastic histiocytic proliferation containing lysosomal clusters of crystal which are almost exclusively kappa light chain immunoglobulin.[1] Central nervous system involvement is extremely rare with only 7 cases reported in the literature.[1],[2],[3],[4],[5],[6],[7],[8] Our case of right temporal lobe involvement, is the 8th case of CSH involving the central nervous system.

   Case Report Top

In September 2019, a 48-year-old female presented with complaint of tingling sensation in the right half of her face that lasted for about 10 days. Upon detection of an intracranial mass radiologically, she was referred in our center's neurosurgery outpatient clinic for further diagnosis and treatment. The patient did not have any active complaints at the after time of admission. She had a history of generalized tonic-clonic seizure starting 5 months earlier.

Physical examination was normal. Cranial magnetic resonance imaging (MRI) revealed a 5 cm lesion in subcortical-deep white matter of the right anterior temporal lobe. The lesion showed hyperintensity in T2A-FLAIR images, hypointensity that may represent central calcification in T2W images and, following intravenous contrast administration, a millimetric nodule with contrast enhancement at the center of the lesion. The lesion caused no significant edema in the surrounding brain parenchyma [Figure 1]. The patient was operated with the pre-diagnosis of a low-grade glial tumor.
Figure 1: Pre-operative radiological findings suggesting a mass lesion in the right temporal lobe, hyperintense on T2W-FLAIR images, with millimetric nodular contrast enhancement and without significant edema in surrounding brain

Click here to view

The gross examination of the excised material revealed gray-pink colored soft tissue fragments of 4 cm.

Intraoperative diagnosis was a perivascular round cell infiltration, and the surgeon was informed that specific diagnosis would be made by permanent sections.

Histopathological examination of the resected mass revealed an inflammatory infiltration consisting predominantly of lymphocytes with perivascular and parenchymal involvement. Furthermore, scattered or clusters of histiocytes with large eosinophilic cytoplasm was noticed [Figure 2]. High power examination showed a number of histiocytes containing intracytoplasmic rod-shaped crystals, while others containing a fibrillary material [Figure 3]. Histochemical stains with phosphotungstic acid hematoxylin (PTAH) stained the crystals purplish blue but congo red and iron did not stain the crystals.
Figure 2: Histiocytes, scattered in the parenchyma or in small clusters, with large eosinophilic cytoplasm and intracytoplasmic rod-shaped crystals (A; H and E, x200, B; H and E, x400)

Click here to view
Figure 3: Microscopic findings of crystal storing histiocytosis. Perivascular and parenchymal lymphoplasmacytic inflammatory infiltration consisting predominantly of lymphocytes and scattered histiocytes in the brain parenchyma (A; H and E, x100), Histochemical staining results. PTAH staining of crystal (B; PTAH, x400), Immunohistochemical staining results. A. Positive staining of histiocytes with CD68 (C; CD 68 × 200). B. Positive staining of plasma cells with CD138 (D; CD 138, x200)

Click here to view

Immunohistochemical studies with CD3, CD20 and CD79a showed staining of lymphocytes suggesting a reactive process. Plasma cells were evident with CD138 and showed polyclonal staining with Lambda and Kappa. Histocytes showed strong positivity with CD68. Ki-67 proliferation index was low and p53 was negative.

According to the histopathological, immunohistochemical and histochemical studies, the patient was diagnosed with CSH.

The patient was further investigated for other hematological malignancies (such as multiple myeloma, monoclonal gammopathy of undetermined significance or lymphoplasmacytic lymphoma) but no other disease or malignancy was present. She was discharged with antiepileptic treatment and was recommended outpatient clinic control. After 16 months of follow-up, the patient presented with radiological findings suggestive of a recurrent lesion, for which continuation of current treatment and close follow-up was recommended.

   Discussion Top

Clinicopathological features of 7 reported cases of CSH involving the central nervous system are summarized in [Table 1]. Of the 7 cases, 2 were male and 5 were female. The ratio of female to male is 2.5. The mean age at time of diagnosis is 35.28 ± 4.2 years, ranging between 20 and 56 years.[1],[2],[3],[4],[5],[6],[7],[8] Our case is a 48-year-old female patient.
Table 1: Clinico-pathological characteristics of cases with crystal-storying histiocytosis of the central nervous system

Click here to view

The mechanisms responsible for crystal deposition in CSH have not been clarified yet, but there are several theories. These theories include; increase in production, abnormal secretion of immunoglobulins and impairment in immunoglobulin clearance. However, there are also studies suggesting that it may be the result of a series of abnormalities that cause crystallization in lysosomal proteins and/or affect intralysosomal degradation.[9] Almost all patients with CSH have an underlying lymphoproliferative disease or a plasma cell disorder such as multiple myeloma, monoclonal gammopathy of undetermined significance or lymphoplasmacytic lymphoma. In addition, drugs (clofazimine), allergic and autoimmune disorders (rheumatoid arthritis, eosinophilic colitis), metabolic disorders such as cystinosis, inflammatory or reactive processes (pulmonary infection, Helicobacter pylori, Crohn disease) and other conditions such as silicosis might be responsible for CSH. The crystal deposits are almost exclusively kappa light chain immunoglobulin, but there are isolated reports of accumulation of other materials such as heavy chain immunoglobulin, clofazimine, Charcot Leyden crystals, cystine and silica.[10],[11],[12],[13],[14] Clinical presentation may vary according to site of the lesion. Patients with central nervous system involvement usually present with complaints of headache, seizures, tremors, numbness, dizziness, loss of strength and blurred vision.[1],[2],[3],[4],[5],[6],[7],[8] Involvement of other organ systems were not reported in any of the patients with central nervous system lesions.[1],[2],[3],[4],[5],[6],[7],[8] Our case had the initial complaint of tingling sensation in the right half of her face.

A mass lesion with contrast enhancement is found in the cranial MRI of patients with central nervous system lesions.[1],[2],[3],[4],[5],[6],[7],[8] Pre-operative diagnoses of CSH involving the central nervous system includes neoplastic, inflammatory processes, diseases involving the white matter and arteriovenous angioma.[1],[2],[3],[4],[5],[6],[7],[8] The patient we present was operated with the pre-diagnosis of a glial tumor.

The gold standard in the diagnosis of CSH is histopathological evaluation. The biopsy material should be evaluated in detail with hematoxylin-eosin stained slides, and then examined by immunohistochemical studies and/or with electron microscopy for the exclusion of other lesions. In hematoxylin-eosin stained sections, epithelioid or spindle-shaped histiocytes with indeterminate cytoplasmic borders, round or oval nuclei and small nucleoli are seen. Some histiocytes contain intracytoplasmic tetragonal, hexagonal or needle-like, usually birefringent and non-polarized crystals.[1],[9],[15],[16] These histiocytes were firstly named “pseudo-Gaucher cell” due to their cytomorphological similarities. However, because the use of this name in other conditions, the histiocytes in CSH were later suggested to be called “pseudo-pseudo-Gaucher cells”.[1] The predominant component in CSH is histiocytes, but diffuse infiltration or small clusters of lymphocytes and plasma cells are also found within the lesion. In the absence of careful microscopic evaluation, the predominant histiocytic appearance might cause an accompanying lymphocytic or plasma cell-derived neoplasia to be missed. In some instances, cytoplasm of the histocytes may show intense eosinophilic and opaque staining. In such cases, crystals may be overlooked causing a misdiagnosis. Also, subtle histopathological findings might cause the lesion to be evaluated as non-specific chronic inflammation or reactive changes.[2],[15]

Histiocytes stain strongly with CD68 and CD163, but show no reaction with desmin, muscle specific actin, myoglobulin, S-100 and CD1a, immunohistochemically. Crystals are usually monoclonal, but immunohistochemical staining may not always be detected. Histochemically, PTAH stains the crystals blue, while PAS staining is variable.[2],[16]

The differential diagnosis of CSH includes hemophagocytic lympho-histiocytic syndrome, rhabdomyoma, granular cell tumor, neoplasms with oncocytic cells, storage diseases such as Gaucher, other histiocytosis such as Erdheim-Chester or Rosai-Dorfman disease, mycobacterial or fungal infections and xanthogranuloma. The presence of crystals, and the immunohistochemical and histochemical staining characteristics are features that make the diagnosis of CSH easier.[1],[9] Rare drug reactions that might cause crystal formation, such as with clofazimine, should also be included in the differential diagnosis. Plasma cell infiltration accompanying the crystals, the clear appearance and negative PAS staining of crystals are indications of a drug reaction.[12]

The prognosis and optimal treatment of CSH are not yet known due to the lack of clinical experience. Patients often receive treatment of the underlying disease. Cases with multiple organ involvement and recurrent disease after surgery are reported, similar to our case recurring after surgery. In addition to surgical treatment, radiotherapy, steroids, mycophenolate, melphalane, lenalidomide, rituximab and cyclophososmide are used in patients with CSH in the central nervous system. Among the cases with follow-up information available, progression of disease occurred within 3 years after the first diagnosis, but mortality due to disease was not detected.[1],[2],[3],[4],[5],[6],[7],[8]

Clarifying unknown points about this very rare entity in the central nervous system and developing of patient management guidelines will be achieved by collecting information through case reports.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Flanagan ME, Keene CD, Louis DN, Juric-Sekhar G. Localized crystal-storing histiocytosis of the posterior fossa. Neuropathology 2018;38:529-34.  Back to cited text no. 1
Costanzi C, Bourdette D, Parisi JE, Woltjer R, Rodriguez F, Steensma D, et al. Crystal-storing histiocytosis: An unusual relapsing inflammatory CNS disorder. Mult Scler Relat Disord 2012;1:95-9.  Back to cited text no. 2
Kaminsky IA, Wang AM, Olsen J, Schechter S, Wilson J, Olson R. Central nervous system crystal-storing histiocytosis: Neuroimaging, neuropathology, and literature review. Am J Neuroradiol 2011;32:E26-8.  Back to cited text no. 3
Rodriguez FJ, Gamez JD, Vrana JA, Theis JD, Giannini C, Scheithouer BW. Immunoglobulin derived depositions in the nervous system: Novel mass spectrometry application for protein characterization in formalin-fixed tissues. Lab Invest 2008;88:1024-37.  Back to cited text no. 4
Johnson M, Mazariegos J, Lewis PJ, Pomakova D. Crystal storing histiocytosis presenting as a temporal lobe mass lesion. Surg Neurol Int 2013;4:112.  Back to cited text no. 5
[PUBMED]  [Full text]  
Orr BA, Gallia GL, Dogan A, Rodriguez FJ. IgA/kappa-restricted crystal storing histiocytosis involving the central nervous system characterized by proteomic analysis. Clin Neuropathol 2014;33:23-8.  Back to cited text no. 6
Woehrer A, Kovacs GG. Clinical neuropathology image 1–2015: Crystal-storing histiocytosis of the central nervous system. Clin Neuropathol 2015;34:4-5.  Back to cited text no. 7
Pezeshkpour G, Steuart TD, Estridge MN. Crystalline encephalopathy: Cerebral immunoprotein deposits and isolated angiitis. Ann Neurol 1985;17:96-9.  Back to cited text no. 8
Galeano-Valle F, Díaz-Crespo FJ, Melero-Martín R, Apaza-Chávez JE, Del-Toro-Cervera J, Demelo-Rodríguez P. Massive generalized crystal-storing histiocytosis associated with extracellular crystalline nephropathy: Clinical, immunohistochemical, and ultrastructural studies of a unique disorder and review of the literature. CEN Case Rep 2019;8:166-72.  Back to cited text no. 9
Beltran M, Khurana S, Gil Y, Lewis JT, Kumar R, Foran JM. Nonimmunoglobulin crystal-storing histiocytosis (CSH): Case report and literature review. Case Rep Hematol 2020;2020:8856411.  Back to cited text no. 10
Dogan S, Barnes L, Cruz-Vetrano WP. Crystal-storing histiocytosis: Report of a case, review of the literature (80 cases) and a proposed classification. Head Neck Pathol 2012;6:111-20.  Back to cited text no. 11
Gebrail F, Knapp M, Perrotta G, Cualing H. Crystalline histiocytosis in hereditary cystinosis. Arch Pathol Lab Med 2002;126:1135.  Back to cited text no. 12
Lewis JT, Candelora JN, Hogan RB, Briggs FR, Abraham SC. Crystal-storing histiocytosis due to massive accumulation of Charcot-Leyden crystals: A unique association producing colonic polyposis in a 78-year old woman with eosinophilic colitis. Am J Surg Pathol 2007;31:481-5.  Back to cited text no. 13
Sukpanichnant S, Hargrove NS, Kachintorn U, Manatsathit S, Chanchairujira T, Siritanaratkul N, et al. Clofazimine-induced crystal-storing histiocytosis producing chronic abdiminable pain in a leprosy patient. Am J Surg Pathol 2000;24:129-35.  Back to cited text no. 14
Reeders J, Arnold C, Chen J, Kirwan P, Lynnhtun K. Crystal-storing histiocytosis leading to the identification of IgG-kappa secreting lymphoplasmacytic lymphoma with crystalline nephropathy. Pathology 2020;52:283-6.  Back to cited text no. 15
Balakrishna J, Chen A, Urken M. Crystal storing histiocytosis clinically mimicking metastatic carcinoma: Report of a case and reviews of literature. Head Neck 2016;38:E95-8.  Back to cited text no. 16

Correspondence Address:
Mine Özşen
Department of Pathology, Uludag University Faculty of Medicine, Bursa
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_373_21

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded53    
    Comments [Add]    

Recommend this journal