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Background
This is a very rare disease usually described in patients with an underlying lymphoproliferative disorder such as a lymphoma or multiple myeloma. Under the microscope, the cells have a characteristic appearance with histiocytes stuffed with crystals, representing immunoglobulins.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE/
PREVALENCERare
DISEASE ASSOCIATIONS CHARACTERIZATION CLOFAZIMINE
Clofazimine-induced crystal-storing histiocytosis producing chronic abdominal pain in a leprosy patient.Sukpanichnant S, Hargrove NS, Kachintorn U, Manatsathit S, Chanchairujira T, Siritanaratkul N, Akaraviputh T, Thakerngpol K.
Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Am J Surg Pathol 2000 Jan;24(1):129-35 Abstract quote Clofazimine-induced crystal-storing histiocytosis is a rare but well-recognized condition in the literature. Besides the common reddish discoloration of the skin, clofazimine produces gastrointestinal disturbances-sometimes severe abdominal pain, prompting exploratory laparotomy, because pathologic and radiologic findings can produce diagnostic difficulties if the pathologic changes caused by clofazimine are not recognized.
The authors report such a case in a leprosy patient to emphasize the importance of history taking, the radiologic abnormalities of the small intestine, and the pathologic findings in small intestine and lymph node biopsies. Clofazimine crystals are red in the frozen section and exhibit bright-red birefringence. However, they are clear in routinely processed histologic sections because they dissolve in alcohol and organic solvents. They also appear as clear crystal spaces during electron microscopic study, but some osmiophilic bodies can be observed. Histiocytosis caused by clofazimine crystals produces infiltrative lesions in radiologic studies mimicking malignant lymphoma or other infiltrative disorders. Associated plasmacytosis in the histologic sections can simulate lymphoplasmacytic lymphoma or multiple myeloma with crystal-storing histiocytosis.
With the knowledge of this rare condition caused by clofazimine, appropriate management to avoid an unnecessary laparotomy is possible.
EOSINOPHILIC COLITIS
*Division of Anatomic Pathology, Mayo Clinic, Rochester, MN Departments of daggerPathology section signSurgery, St Dominic-Jackson Memorial Hospital, Jackson, MS double daggerDepartment of Gastroenterology, University of Mississippi School of Medicine, Jackson, MS.
Crystal-storing histiocytosis is a rare diagnosis that to date has only been associated with 2 conditions: intracytoplasmic accumulation of crystallized immunoglobulins in patients with lymphoproliferative disorders or plasma cell dyscrasias, and histiocytic accumulations of phagocytosed clofazimine, a drug used to treat lepromatous leprosy.
We describe a 78-year-old woman with a past medical history of dermatologic mastocytosis and peripheral eosinophilia who presented with diarrhea and weight loss, and was found at colonoscopy to have polyposis limited to the right and transverse colon. She eventually underwent subtotal colectomy to remove the segment of polyposis. At gross examination, the colonic mucosa contained numerous polyps ranging from 1 to 7 mm which on histologic evaluation proved to represent mucosal and submucosal collections of histiocytes whose cytoplasm was distended by numerous brightly eosinophilic crystals. An intense eosinophilic infiltrate surrounded the histiocyte collections and also mildly involved the intervening colonic mucosa and superficial submucosa. Electron microscopy confirmed the presence of intracytoplasmic material identical to Charcot-Leyden crystals within histiocytes, representing the breakdown products of degranulated eosinophils.
This is the first reported case of crystal-storing histiocytosis produced by massive accumulation of Charcot-Leyden crystals in eosinophilic colitis.FIBROSCLEROSIS
Crystal-storing histiocytosis and immunocytoma associated with multifocal fibrosclerosis.Garc-ia JF, Sanchez E, Lloret E, Martin J, Piris MA.
Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain.
Histopathology 1998 Nov;33(5):459-64 Abstract quote AIMS: Crystal-storing histiocytosis is a rare disorder described in patients with lymphoproliferative diseases, mainly in cases of multiple myeloma but also in lymphoplasmacytic lymphoma (immunocytoma). Most cases involve one single organ which, in the majority, is related directly to the presence of tumour. We describe a 44-year-old man with a clinical picture of multifocal fibrosclerosis (with mesenteric panniculitis, peritoneal, mediastinal and orbital fibrosis) in which the autopsy showed a systemic infiltrate of crystal-storing histiocytes and functional alteration of the organs involved, associated with IgG-kappa type immunocytoma.
METHODS AND RESULTS: Histology showed a systemic infiltration, with a predilection for adipose tissue, by a diffuse cellular infiltrate composed of small lymphocytes, plasmacytoid lymphocytes and plasma cells, admixed with large number of crystal-storing histiocytes. Intracytoplasmic crystals were not identified either in the plasma cells or plasmacytoid lymphocytes. The neoplastic cells and the crystalline inclusions displayed reactivity with antibodies for IgG and the kappa light chain. A polymerase chain reaction study for the IgH gene showed a monoclonal rearrangement. Ultrastructural studies showed needle-shaped crystals surrounded by a single unit membrane.
CONCLUSION: This case is, to the authors' knowledge, the first to be described in which crystal-storing histiocytosis is associated with a clinical picture of multifocal fibrosclerosis, which suggests that lymphoproliferative processes should be considered in the differential diagnosis of the various conditions associated with multifocal fibrosclerosis.
LYMPHOMA, EXTRANODAL
- Pulmonary extranodal marginal zone lymphoma with massive crystal storing histiocytosis.
Fairweather PM, Williamson R, Tsikleas G.
Am J Surg Pathol. 2006 Feb;30(2):262-7. Abstract quote
We present an incidentally discovered, unusual case of pulmonary bronchial mucosa-associated lymphoid tissue lymphoma associated with massive crystal storing histiocytosis in a 69-year-old woman. The neoplastic process was masked by large numbers of epithelioid and spindled histiocytes containing crystalline material.
Histochemical stains showed intracytoplasmic crystals and immunoperoxidase staining confirmed the histiocytic nature of the swollen cells. Electron microscopy demonstrated the characteristic appearance of immunoglobulin crystals. Lymphoepithelial lesions were identified on immunohistochemical staining, compounding suspicions of an underlying lymphoid neoplasm. Molecular studies later revealed a monoclonal B-cell population. The patient had no systemic evidence of a paraproteinemia. Crystal storing histiocytosis is a rare phenomenon in which macrophages accumulate light chain or immunoglobulin crystalline inclusions. The disease may be systemic, or localized as in this case.
It is usually associated with the excess production of a monoclonal immunoglobulin, although there have been many case reports without this feature. An overview of crystal storing histiocytosis is given.MULTIPLE MYELOMA
Multiple myeloma, IgA kappa type, accompanying crystal-storing histiocytosis and amyloidosis.Takahashi K, Naito M, Takatsuki K, Kono F, Chitose M, Ooshima S, Mori N, Sakuma H, Uchino F.
Acta Pathol Jpn 1987 Jan;37(1):141-54 Abstract quote An autopsy case of multiple myeloma, IgA kappa type, accompanying systemic crystal-storing histiocytosis and generalized amyloidosis, is reported. Besides multiple destructive lesions in the skeletal bones, nodular myeloma cell infiltrates were scattered in the liver, spleen, and both kidneys. Not only in these lesions but also in the reticuloendothelial organs, crystal-storing macrophages appeared dispersively or in clusters. Electron microscopically, numerous crystalline inclusions contained in the cytoplasm of macrophages were membrane-bound and of variable configuration, comprising of a homogeneous electron-lucid material. Enzyme cytochemically, almost all of the inclusions showed acid phosphatase activity.
On the basis of the results obtained from the immunohistochemical, immunofluorescent and immunoelectron microscopic studies, it was considered that the crystalline inclusions stored in the macrophages were derived from IgA kappa immunoglobulin secreted from the myeloma cells and were formed within secondary lysosomes by crystallization during lysosomal digestion and degradation of the ingested immunoglobulin by macrophages.
Generalized amyloidosis developed in different sites from those of the crystal-storing histiocytosis and were proven immunohistochemically to belong to AL amyloidosis probably derived from a certain group of A kappa precursor protein.
Crystal-storing histiocytosis and crystalline tissue deposition in multiple myeloma.
Yamamoto T, Hishida A, Honda N, Ito I, Shirasawa H, Nagase M.
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Arch Pathol Lab Med 1991 Apr;115(4):351-4 Abstract quote Systemic distribution of crystal-storing histiocytes, increasing in number, and widespread crystalline tissue deposition were found in a 75-year-old man with a 5-year history of IgG-kappa-type multiple myeloma associated with corneal opacity and chronic renal failure.
Characteristic crystalline inclusions were present not only in myeloma cells but also in cornea, epithelial cells of glomeruli, tubuli, Bowman's capsules, and choroid plexus. Histiocytes had particularly infiltrated the renal interstitium. These inclusions were positive by immunofluorescence for kappa light and gamma heavy chains.
By electron microscopy, the inclusions were filled with fine crystalline hexagonal columns, each possessing a core structure. Of various factors generally considered responsible for renal failure in multiple myeloma, marked infiltration of histiocytes and the nephrotoxic effects of light chain appeared most relevant in the present case.
RHEUMATOID ARTHRITIS
Solitary crystal-storing histiocytosis of the tongue in a patient with rheumatoid arthritis and polyclonal hypergammaglobulinemia.Bosman C, Camassei FD, Boldrini R, Piro FR, Saponara M, Romeo R, Corsi A.
Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy
Arch Pathol Lab Med 1998 Oct;122(10):920-4 Abstract quote A 73-year-old woman with a long history of rheumatoid arthritis and polyclonal hypergammaglobulinemia developed a solitary mass in the tongue, which on morphologic and immunohistochemical analyses was consistent with crystal-storing histiocytosis, a rare condition commonly described in association with clonal lymphoplasmacytic disorders.
The lesion consisted of a localized collection of histiocytes filled with numerous eosinophilic crystals immunoreactive for both kappa and lambda light chain and gamma heavy chain antibodies. Mature lymphocytes and plasma cells were present both throughout and around the lesion.
Since a clonal lymphoplasmacytic neoplasm was ruled out by clinical and immunohistochemical studies, we consider that, in this case, crystal-storing histiocytosis was consequent to polyclonal hypergammaglobulinemia and suggest that this rare histiocytosis is not specific to lymphoplasmacytic neoplasms, but may represent a reaction to high values of normal (or abnormal) immunoglobulins.
PATHOGENESIS CHARACTERIZATION GENERAL
Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: molecular analysis of a disorder with rapid clinical course and review of the literature.Lebeau A, Zeindl-Eberhart E, Muller EC, Muller-Hocker J, Jungblut PR, Emmerich B, Lohrs U.
Pathologisches Institut and the Medizinische Klinik-Klinikum Innenstadt der Ludwig-Maximilians-Universitat Munchen, Germany.
Blood 2002 Sep 1;100(5):1817-27 Abstract quote Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy. The intracellular crystal formation is almost always accompanied by the expression of kappa light chains. However, the exact mechanism for the storage has not been clarified until now.
We report a case of generalized CSH in a 73-year-old man who presented with IgA kappa paraproteinemia and paraproteinuria. The initially observed CSH in the bone marrow biopsy was associated with the clinical and pathomorphologic features of a monoclonal gammopathy of undetermined significance. The progression of disease could not be affected by steroid therapy and the patient died of septic shock 7 months after detection of CSH. At the time of autopsy there was evidence for multiple myeloma and generalized CSH. Two-dimensional gel electrophoresis of liver tissue combined with immunoblotting revealed the massive storage of heavy chains of alpha type and light chains of kappa type, each in a monoclonal pattern. Analysis of the stored kappa light chain by nanoelectrospray-ionization mass spectrometry indicated that it belongs to the variable (kappa)I variability subgroup.
We identified some unusual amino acid substitutions including Leu59, usually important for hydrophobic interactions within a protein, at a position where it has never been previously described in plasma cell disorders. In conclusion, we present the first case of CSH with molecular identification of the stored kappa subgroup and detection of unusual amino acid substitutions.
Our results suggest that conformational alterations induced by amino acid exchanges represent a crucial pathogenic factor in CSH.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS Monoclonal gammopathy common
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS KIDNEY
Crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder.Sethi S, Cuiffo BP, Pinkus GS, Rennke HG.
Division of Renal Pathology and Electron Microscopy, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Am J Kidney Dis 2002 Jan;39(1):183-8 Abstract quote Intracellular crystal formation in histiocytes in multiple myeloma and other lymphoproliferative disorders is an uncommon presentation. In all cases, crystal formation is associated with accumulation of histiocytes containing light chain or immunoglobulin inclusions, and the disorder has been termed crystal-storing histiocytosis.
We report a case of crystal-storing histiocytosis affecting the kidney with prominent infiltration of the mesangium by large mononuclear and multinuclear cells that contained eosinophilic crystalline material in the setting of a low-grade B-cell lymphoproliferative disorder. The interstitium did not contain similar crystal-containing histiocytes. On electron microscopy, the mononuclear and multinuclear cells in the mesangium were filled with rhomboid and needle-shaped crystals. Immunofluorescence studies showed the material to be positive for lambda light chains but negative for kappa light chains.
To our knowledge, this is the first report of crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder with an immunophenotype of a marginal zone lymphoma and of exclusive expansion of the mesangium by infiltrating histiocytes containing needle-shaped and rhomboid crystals that were positive for lambda light chains.
We report this case to illustrate an unusual finding of mesangial infiltration by crystal-storing histiocytes, and we review the literature of renal involvement by crystal-storing histiocytosis and crystal deposition in lymphoproliferative disorders.
LACRIMAL GLANDS
Extranodal marginal zone B-cell lymphoma of the lacrimal gland associated with crystal-storing histiocytosis.Coupland SE, Foss HD, Hummel M, Stein H.
Department of Pathology, University Hospital Benjamin Franklin, Freie Universitat, Hindenburgdamm 30, D-12200 Berlin, Germany.
Ophthalmology 2002 Jan;109(1):105-10 Abstract quote OBJECTIVE: Crystal-storing histiocytosis (CSH) is a very rare immunoglobulin (Ig) deposition disorder that can be associated with B-cell neoplasms as well as some reactive Ig-secreting lymphoproliferative disorders. This article reports the clinical, histopathologic, and molecular biologic findings of CSH in association with an extranodal marginal zone lymphoma (EMZL) of the lacrimal gland.
DESIGN: Interventional case report with clinicopathologic correlation.
INTERVENTION: Treatment consisted of conjunctival and orbital biopsies, as well as low-dose radiation of the left orbit.
METHODS: Histopathologic findings of the conjunctival and orbital biopsies were compared. Further, extensive immunohistochemistry, polymerase chain reaction (PCR) for the detection of Ig heavy chain (IgH) gene rearrangement, Gene Scan analysis, and DNA sequencing were performed on all tissues.
RESULTS: The tumor manifestations in the specimens demonstrated a similar morphologic and immunophenotypic characteristics consistent with the diagnosis of EMZL. Immunoglobulin H PCR and Gene Scan analysis showed B cells derived from the same clone. In association with the orbital EMZL were large accumulations histiocytes filled with refractile crystals, consistent with the diagnosis of CSH.
CONCLUSIONS: The current case describes an EMZL of the lacrimal gland appearing 5 years after excision and low-dose radiation of a conjunctival lymphoma. The orbital recurrence was associated with surrounding CSH, a rare Ig storage disorder more often reported in patients with multiple myeloma or lymphoplasmacytic lymphoma or immunocytoma. Ophthalmic pathologists should be aware of the diagnosis when reviewing orbital biopsies, because difficulties may arise when the crystal-storing macrophages occupy more tissue space than the Ig-secreting cells or when they resemble cell types such as rhabdomyoblasts.
LUNGS
- Pulmonary crystal-storing histiocytoma.
Ionescu DN, Pierson DM, Qing G, Li M, Colby TV, Leslie KO.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Arch Pathol Lab Med. 2005 Sep;129(9):1159-63. Abstract quote
We describe the case of a 50-year-old woman with a lung tumor composed of crystal-storing histiocytes. These cells and associated plasma cells failed to show clonal light chain restriction, and the patient had no associated hematologic disorder. The differential diagnosis included crystal-storing histiocytosis, characterized by accumulation of crystallized immunoglobulins, a rare manifestation of monoclonal gammopathies/plasma cell dyscrasias. Crystal-laden histiocytes have previously been described in many organs.
Four reports have described crystal-storing histiocytosis in the lung, always associated with a lymphoproliferative disorder. The present patient, 1 other case from our archive, and 1 case reported in the literature, all without an association with lymphoproliferative disorder, make a full description and definition of this lesion appropriate. The morphology, immunohistochemical profile, and electron microscopic features are described herein, and the term pulmonary crystal-storing histiocytoma is proposed.
A practical algorithm is presented for the assessment of solitary lung masses composed of large histiocytic cells.
Pulmonary crystal-storing histiocytosis and extranodal marginal zone B-cell lymphoma associated with a fibroleiomyomatous hamartoma.Sun Y, Tawfiqul B, Valderrama E, Kline G, Kahn LB.
Departments of Pathology and Cardiothoracic Surgery and the Divisions of Surgical Pathology and Pediatric Pathology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, NY.
Ann Diagn Pathol 2003 Feb;7(1):47-53 Abstract quote Crystal-storing histiocytosis (CSH) is a rare disorder occurring in patients with lymphoproliferative diseases, predominantly in cases of multiple myeloma and low-grade B-cell lymphoma. To the best of our knowledge, only three cases of pulmonary CSH have been reported in the English literature and one of them was associated with a low-grade B-cell lymphoma (immunocytoma).
We document a case of a 59-year-old man with bilateral lung masses in which a right middle lobe pulmonary lobectomy specimen showed CSH associated with an extranodal marginal-zone B-cell lymphoma. A single nodule showing features of fibroleiomyomatous hamartoma was present in a wedge biopsy specimen from the left lung.
Two nodules within the right middle lobe were composed of sheets of histiocytic cells with abundant eosinophilic cytoplasm resembling striated muscle cells. In addition, there were nodular aggregates and a more diffuse infiltrate of small slightly atypical centrocyte-like lymphocytes, as well as bronchial lymphoepithelial lesions. Immunohistochemistry performed on paraffin-embedded sections demonstrated that the histiocytic cells were immunoreactive with the KP-1 (CD68) antibody while the lymphocytic infiltrate was CD20 positive, co-expressed for CD43, and was negative for CD3, CD5, and CD10.
Genotypic analysis demonstrated the presence of an immunoglobulin heavy-chain gene rearrangement, indicating the presence of a monoclonal B-cell population. These features were consistent with pulmonary CSH associated with extranodal marginal-zone lymphoma of baltoma type.
Pulmonary immunocytoma with massive crystal storing histiocytosis: a case report with review of literature.Prasad ML, Charney DA, Sarlin J, Keller SM.
Department of Pathology, The New York Hospital-Cornell Medical Center, New York 10021, USA.
Am J Surg Pathol 1998 Sep;22(9):1148-53 Abstract quote An unusual immunocytoma (lymphoplasmacytoid lymphoma) composed predominantly of sheets of globoid and spindle-shaped crystal-storing histiocytes was detected incidentally in the right lung of a 72-year-old woman. Scattered lymphoplasmacytic aggregates within the tumor had monoclonality with anti-kappa immunoglobulin (Ig) M antibodies.
The crystals were outlined positively by the same antibodies. They stained an intense blue with phosphotungstic acid-hematoxylin (PTAH) and were found during electron microscopy to be membrane bound and also within type I pneumocytes and the extracellular space. Excessive production of kappa IgM by neoplastic low-grade lymphoplasmacytoid cells of B-cell origin in an altered intra- or extracellular milieu may lead to crystallization and phagocytosis by reactive histiocytes. Review of the literature revealed seven more cases: four in the head and neck, and one each in the skin, the lymph node, and the lung. IgM was the most frequently crystallizing immunoglobulin (four of seven) and all had kappa light chains.
The lesion needs to be differentiated from neoplastic and nonneoplastic histiocytic and lymphoplasmacytic disorders. The difference with bronchial mucosa-associated lymphoid tissue lymphoma and marginal zone lymphoma is, perhaps, semantic.
Recurrent crystal-storing histiocytosis of the lung in a patient without a clonal lymphoproliferative disorder.Jones D, Renshaw AA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02115, USA.
Arch Pathol Lab Med 1996 Oct;120(10):978-80 Abstract quote A 54-year-old woman developed an asymptomatic solitary lung mass, which recurred 10 years after resection. Both lesions consisted of a localized collection of intra-alveolar and interstitial macrophages filled with numerous eosinophilic cytoplasmic crystals. The crystals were non-birefringent, periodic acid-Schiff-negative, and showed polytypic reaction with both kappa and lambda light chains, and alpha, mu, and gamma heavy chains.
No immunoglobulin gene rearrangements were detected. This lesion is consistent with crystal-storing histiocytosis, which has been reported in association with plasmacytoma. However, in this case, the absence of monotypic immunoglobulin staining within the crystals or the surrounding plasma cells, the absence of DNA rearrangements, and the long asymptomatic course raise the possibility that this lesion may be reactive.
Similar lesions are seen in the lungs of mice with immune defects. Crystal-storing histiocytosis may represent a general reaction pattern to excess immunoglobulin.
PAROTID GLAND
Massive crystal-storing histiocytosis associated with low-grade malignant B-cell lymphoma of MALT-type of the parotid gland.Llobet M, Castro P, Barcelo C, Trull JM, Campo E, Bernado L.
Department of Pathology, Hospital Dr. Josep Trueta, Girona, Spain.
Diagn Cytopathol 1997 Aug;17(2):148-52 Related Articles, Links
Massive crystal-storing histiocytosis associated with low-grade malignant B-cell lymphoma of MALT-type of the parotid gland.Llobet M, Castro P, Barcelo C, Trull JM, Campo E, Bernado L.
Department of Pathology, Hospital Dr. Josep Trueta, Girona, Spain.
Massive crystal deposition is unusual in lymphoproliferative disorders. In this report, a mucosa-associated lymphoid tissue (MALT) low-grade B-cell lymphoma of the parotid gland containing large numbers of crystal-storing histiocytes is described. The patient, an 81-yr-old female, presented with a history of long-standing left parotid gland enlargement. FNA cytology of the tumor showed a lymphoplasmacytic infiltrate and sheets of large benign histiocytes with abundant eosinophilic intracytoplasmic inclusions. Paraffinsection immunohistochemistry performed on the cell block demonstrated that the histiocytic cells were immunoreactive for the KP-1 (CD-68) antibody and monotypic for cytoplasmic IGM and L-light chain. The cytological diagnosis was consistent with a low-grade B-cell lymphoma with plasmacytic differentiation associated with crystal-storing histiosis. A periparotid lymph node was biopsied and showed involvement by a monocytoid B-cell lymphoma with plasmacytic differentiation and crystal-storing histiocytosis in the pericapsular region.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL FOLLICULAR LYMPHOMA
Intracytoplasmic immunoglobulin crystals in follicular lymphoma.Wada R, Ebina Y, Kurotaki H, Yagihashi S.
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan.
Hum Pathol 2002 Nov;33(11):1141-4 Abstract quote We report a case of follicular lymphoma with crystal inclusions. Swollen lymph nodes taken from the left neck of a 53- year-old Japanese woman were replaced by follicular proliferation of atypical centroblastic and centrocytic cells with intracytoplasmic crystal inclusions.
The crystals were confined to lymphoma cells and were not found in histiocytes. Lymphoma cells were positively immunostained with lambda light chain and mu heavy chain, but the crystals were only weakly so. In situ hybridization of light chains disclosed a monoclonal expression of lambda light chain mRNA in lymphoma cells. The crystals had a periodic linear substructure with about 5-nm intervals.
The worldwide literature reports 8 cases, including the current case of non-Hodgkin's lymphoma with crystals confined to the neoplastic cells. The cases did not accompany paraproteinemia and crystal-storing histiocytosis and appear to follow a favorable clinical outcome.
LYMPHOPLASMACYTIC LYMPHOMA Subcutaneous crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma (immunocytoma)
Kaufmann O, Hansen A, Deicke P, Burmester GR, Dietel M.
Institute of Pathology, Charite University Hospital, Berlin, Germany.
Pathol Res Pract 1996 Nov;192(11):1148-51 Abstract quote. A case of massive crystal-storing histiocytosis with extensive involvement of the subcutaneous 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 variables shapes, were occasionally membrane-bound and measured up to 6 microns. The finding are briefly discussed.
MONOCYTOID B-CELL LYMPHOMA
Transformation of monocytoid B-cell lymphoma to large cell lymphoma associated with crystal-storing histiocytes.Thorson P, Hess JL.
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Arch Pathol Lab Med 2000 Mar;124(3):460-2 Abstract quote We report a case of crystal-storing histiocytosis associated with large cell lymphoma in a patient with a history of monocytoid B-cell lymphoma 10 years previously.
The cervical lymph node biopsy showed a diffuse proliferation of large lymphocytes with vesicular nuclear chromatin and distinct nucleoli. These lymphocytes were associated with numerous immunoglobulin lambda light-chain crystal-storing histiocytes, which morphologically resembled rhabdomyoblasts. Occasional lymphoid cells also showed large immunoglobulin crystals.
This case establishes the association of crystal-storing histiocytes with lymphomas of mucosa-associated lymphoid tissue and emphasizes the need for immunophenotyping to distinguish these unusual cases from other tumors, particularly adult rhabdomyomas.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE ELECTRON MICROSCOPY
Kappa-type light chain crystal storage histiocytosis.Terashima K, Takahashi K, Kojima M, Imai Y, Tsuchida S, Migita S, Ebina S, Itoh C.
Acta Pathol Jpn 1978 Jan;28(1):111-38 Abstract quote An autopsy case of systemic histiocytosis with excessive deposition of kappa-type light chain crystals was reported in a 58 year-old man who had consistently showed kappa-type light chain paraproteinemia, Bence Jones proteinuria and hypogammaglobulinemia for about 10 years until his death. However, no bony destruction was found by repeated X-ray examinations.
At autopsy, extensive hyperplasia of crystal-storing histiocytes was observed in the bone marrow, spleen, liver, lymph nodes, interstitial tissues of visceral organs and loose connective tissues. In the bone marrow and some other tissues, mild proliferation of plasmocytoid cells containing small crystals were found.
Histochemically the crystals positively stained with various methods for amino acids and proteins, especially with Weigerts' method for fibrin.
Ultrastructurally intralysosomal crystal deposition was confirmed in the storage histiocytes and derivation of the crystals from Golgi's sacculi in the plasmocytoid cells was suggested. Biochemically the crystals were regarded as mainly consisting of dimers of a variable half of light chain immunoglobulin and immunochemically and immunohistochemically reacted to anti-kappa type light chain serum.
Such a generalized storage histiocytosis may be secondarily induced by immunoglobulin synthesized in plasmocytoid cells.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES GAUCHER DISEASE
Gammopathy-related crystal-storing histiocytosis, pseudo- and pseudo-pseudo-Gaucher cells. Critical commentary and mini-review.
Schaefer HE.
Pathologisches Institut der Universitat, Freiburg, Germany.
Pathol Res Pract 1996 Nov;192(11):1152-62 Abstract quote Commenting on a case report of dermal immunocytoma with crystal-storing histiocytes, a short review is given on the phenomena related to crystallization of monoclonal immunoglobulins within plasma cells, in the extracellular space, or within the lysosomal compartment of macrophages.
Paraprotein crystallization is supported by hydrophobicity, poor solubility in the cold or at acid pH, and there are few reports on structural defects of crystal-forming myeloma proteins which are supposed to promote either their crystallization or impaired intralysosomal degradation. In the hitherto known cases of crystal histiocytosis, immunoglobulins of light chain type kappa have been exclusively involved in the process of macrophage storage.
Accumulation of paraprotein-related crystals in macrophages may mimic the appearance of Gaucher cells or of the so-called pseudo-Gaucher cells seen in chronic myelogeneous leukaemia. With regard to their lightmicroscopical and ultrastructural differences to both, Gaucher cells and pseudo-Gaucher cells, paraproteinaemia-related crystal-storing macrophages may be denoted as pseudo-pseudo-Gaucher cells (PPGC). Human PPGC are similar to constitutive crystal-storing histiocytes known from inbred C57 BL-6 mice.
The distribution of PPGC may be limited to the realm of a plasmacytoma or immunocytoma, but there are also cases with systemic involvement of the RES similar to Gaucher disease.
RHABDOMYOMA
Crystal-storing histiocytosis associated with lymphoplasmacytic neoplasms. Report of three cases mimicking adult rhabdomyoma.Kapadia SB, Enzinger FM, Heffner DK, Hyams VJ, Frizzera G.
Department of Otolaryngic, Armed Forces Institute of Pathology, Washington, DC.
Am J Surg Pathol 1993 May;17(5):461-7 Abstract quote Massive crystal deposition is rare in lymphoplasmacytic (LPc) or plasma cell neoplasms.
We report three cases in which the accumulation of crystals in histiocytes closely reproduced the histologic features of adult rhabdomyoma. The patients, all female, aged 18, 77, and 78 years, presented with tumor of cervical lymph nodes (two cases) or the otolaryngic mucosa (two cases). In addition, two patients had monoclonal serum or urine immunoglobulin (IgM-kappa-1, unknown-1), and one had renal and bone marrow involvement on biopsy. This last patient died of acute renal failure at 5 months, another was alive without disease at 8 years, and the remaining one was lost to follow-up. Lymph nodes, mucosae, and kidney showed a neoplastic LPc infiltrate masked by sheets of large benign histiocytes containing sheaves of crystals. Paraffin-section immunohistochemistry demonstrated monoclonal staining of the LPc cells in all cases (IgM-kappa-2, IgA-kappa-1) and of the crystals (IgM-kappa) in one case. In all patients, the crystal-containing cells were positive for KP-1 (CD68), but not for desmin, muscle-specific actin, or myoglobin.
These findings suggest that, in any case of adult rhabdomyoma in which the histologic findings are not typical, a crystal-storing histiocytosis should be ruled out: recognition of the atypical LPc component and the histiocytic immunophenotype of the crystal-storing cells will help prevent a serious misdiagnosis.
WEBER-CHRISTIAN DISEASE
Crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma mimicking Weber-Christian disease: immunohistochemical, ultrastructural, and gene-rearrangement studies.Harada M, Shimada M, Fukayama M, Kaneko T, Kitazume K, Weiss SW.
Department of Diagnostic Pathology, Kanto Teishin Hospital, Tokyo, Japan.
Hum Pathol 1996 Jan;27(1):84-7 Abstract quote A case of crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma is presented. Unlike previous cases, this patient presented with signs and symptoms suggestive of Weber-Christian disease.
Biopsy of subcutaneous nodules showed numerous deposits of crystal-storing histiocytes with lymphoplasmacytic cells, the latter exhibiting light chain restriction (lambda-chain) with a predominance of immunoglobulin (Ig)G heavy chain. Polymerase chain reaction (PCR) analysis of CDR-II* region of the immunoglobulin heavy chain locus confirmed monoclonality of the lymphoplasmacytic cells in the nodule. Electron microscopy showed polygonal-shaped amorphous crystals, characteristic of immunoglobulin in the histiocytic cells.
Crystal-storing histiocytosis should be examined by immunohistochemical and DNA analysis to confirm or exclude the possibility of lymphoplasmacytic lymphoma.
PROGNOSIS CHARACTERIZATION GENERAL Dependent upon the underlying lymphoproliferative disorder or disease process
TREATMENT CHARACTERIZATION GENERAL Dependent upon the underlying lymphoproliferative disorder or disease process Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation
Commonly Used Terms
This is a glossary of terms often found in a pathology report.Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscopeSurgical Pathology Report
Examine an actual biopsy report to understand what each section meansSpecial Stains
Understand the tools the pathologist utilizes to aid in the diagnosisHow Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurateGot Path?
Recent teaching cases and lectures presented in conferences
Last Updated March 13, 2007
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