Intranuclear Inclusions in Plasma Cells and Lymphocytes from Patients with Monoclonal Gammopathies

Abstract

Ultrastructural studies of intranuclear inclusions in plasma cells and lymphocytes from patients with different forms of monoclonal gammopathies are presented. The inclusions occurred as two distinct morphologic and ultrastructural types. In three patients, two with IgA myeloma and one with Waldenström's macroglobulinemia, the inclusions were variably PAS-positive in routine sections and composed of electron-light amorphous material ultrastructurally. In one patient with an IgG monoclonal gammopathy, the plasma cells contained inclusions that were PAS negative by light microscopy and primarily osmiophilic ultrastructurally. One patient with an immunoblastic sarcoma and an IgM monoclonal had plasma cells with numerous inclusions of both types. There was a distinct spatial relationship between the electron-light amorphous material and the osmiophilic deposits in many of the inclusions in cells from this patient. In cells from two patients in which osmiophilic inclusions were found, they were present in the cytoplasm as well as the nucleus. The intranuclear inclusions appeared to develop from accumulation of material in the perinuclear cisterna, resulting in single or multiple invaginations of the nuclear structure.

Follicular lymphoma with prominent Dutcher body formation: a pathologic study of 3 cases in comparison with nodal or splenic lymphoplasmacytic lymphoma and marginal zone lymphoma

“…Although FL has been occasionally described to display plasmacytic differentiation and contain rare Dutcher bodies in individual cases [7,30], those with extensive Dutcher body formation, as shown in the current study, are extremely rare, and to the best of our knowledge, only a single case was reported by our group in the English literature [28]. Although a Dutcher body is morphologically characterized by a round, usually single intranuclear inclusion, and a Russell body is considered as its cytoplasmic counterpart, both have been illustrated as globules of accumulated Ig in the rough endoplasmic reticulum [19]. In contrast to Russell bodies, Dutcher bodies are formed by an invagination of Ig-rich cytoplasm or perinuclear cisternae of rough endoplasmic reticulum into the nuclear compartment per electronic microscopic studies [19,24] and are, thus, considered to be pseudonuclear inclusions.…”

“…Although a Dutcher body is morphologically characterized by a round, usually single intranuclear inclusion, and a Russell body is considered as its cytoplasmic counterpart, both have been illustrated as globules of accumulated Ig in the rough endoplasmic reticulum [19]. In contrast to Russell bodies, Dutcher bodies are formed by an invagination of Ig-rich cytoplasm or perinuclear cisternae of rough endoplasmic reticulum into the nuclear compartment per electronic microscopic studies [19,24] and are, thus, considered to be pseudonuclear inclusions. The reactivity of inclusion bodies to anti-Ig in our cases was consistent with the previous findings and confirmed their nature as Dutcher bodies.…”

“…The formation of Dutcher bodies has been studied previously in B-cell lymphoid neoplasms, mainly in plasma cell myeloma/dyscrasia [15,17,19], LPL/WM [15,23], and MALT lymphoma [24]. Dutcher and Fahey [22] initially described periodic acid-Schiff stain-positive substances in the intranuclear inclusions in WM.…”

“…Dutcher and Fahey [22] initially described periodic acid-Schiff stain-positive substances in the intranuclear inclusions in WM. Although an early study by Brittin et al [15] using electron microscopy showed nuclear elaboration of protein in intranuclear inclusions and suggested that Dutcher bodies might represent true nuclear inclusions, subsequent investigations demonstrated ultrastructural evidence of invagination of Ig-rich cytoplasm or perinuclear cisternae of rough endoplasmic reticulum with accumulated Ig into the nuclear compartment [19,24]. However, the mechanism for the formation of Dutcher bodies is currently unclear despite these studies.…”

“…They are more frequently seen in B-cell neoplasms that demonstrate plasmacytic or plasmacytoid differentiation, including plasma cell myeloma [11][12][13][14][15][16][17][18][19], monoclonal gammopathy of undetermined significance [19,20], LPL [15,[21][22][23], and MZL [24][25][26][27]. The presence of Dutcher bodies in other types of Bcell lymphoma is rare [28][29][30], and prominent Dutcher body formation in FL has not been well characterized, except in a rare case report [28].…”