Cytoplasmic crystals in multiple myeloma-associated Fanconi's syndrome. A morphological study including immunoelectron microscopy

We report a case of Fanconi's syndrome associated with multiple myeloma, which displayed some unusual features. Although serum immunoelectrophoresis showed no spike, urine electrophoresis revealed monoclonal kappa light chain. The myeloma cells in multiple organs including bone marrow, lymph nodes, spleen, and kidneys were distended with characteristic intracytoplasmic crystals. In the kidneys, identical intracytoplasmic crystals were found in some proximal tubules, distal tubules, collecting ducts, glomerular cells (mostly parietal epithelial and endocapillary cells), and renal interstitial cells. Only monoclonal kappa light-chain protein was demonstrated in these crystals by immunofluorescence and immunoperoxidase techniques, a finding confirmed for the first time (to our knowledge) by immunoelectron microscopic study of the renal biopsy specimens.     

Crystals in an Oligodendroglioma: An Optical, Histochemical, and Ultrastructural Study

The report describes an oligodendroglioma that was examined in four biopsies and contained a large number of intracytoplasmic crystals. The crystals appeared in neoplastic cells with eosinophilic cytoplasms and eccentric nuclei. They were positive to periodic acid-Schiff stain and resistant to diastase. A lysosomal genesis of the crystals is proposed on the basis of a transition observed between lysomal bodies with lipid droplets and those with crystalloid electron-dense structures. The morphologic and histochemical features of these crystals are compared to those in other tumors, lesions, and non neoplastic cells.     

Intracytoplasmic and intranuclear Reinke's crystals in a testicular Leydig-cell tumor diagnosed by fine-needle aspiration cytology: a case report with review of the literature

We report on the cytopathologic findings of a Leydig-cell tumor of the testis in a young adult male with no evidence of endocrine dysfunction. The preoperative diagnosis was based on fine-needle aspiration cytology (FNAC) alone, which was subsequently confirmed on histopathology. The present case was of interest on account of the paucity of literature regarding the cytodiagnosis of this lesion. In addition, the finding of intracytoplasmic lipofuscin pigment and several intracytoplasmic as well as intranuclear Reinke's crystals served to clinch the diagnosis on FNA. Therefore, the use of FNAC, especially in the presence of diagnostic Reinke's crystals, may vitiate the need for more invasive biopsy procedures in the preoperative diagnosis of testicular Leydig-cell tumors.     

Hepatoid carcinoma of the skin: spontaneous rat skin hepatoid carcinoma with eosinophilic globules and crystals immunoreactive to α-1-antitrypsin

We present a case of hepatoid carcinoma of the abdominal skin in a male Wistar rat. Histopathologically, this carcinoma resembled human hepatocellular carcinoma with respect to trabecular-sinusoidal structures. Carcinoma tissues contain numerous eosinophilic globules and crystals, and in this case, we found the characteristic eosinophilic globules in the hepatoid carcinoma cells and the crystals in the extracellular portions. Vivid carcinoma cells full of eosinophilic globules were present near the necrotic areas in tumor tissue, wherein quadrate crystals unstained with eosin were observed. PAS staining after diastase digestion revealed that the globules were PAS positive and diastase resistant. In addition, we found that the hepatoid carcinoma cells were immunoreactive for α-1-antitrypsin (anti-A1AT) antibody with the globules and crystals staining peripherally, and a central unstained region. Ultrastructural study of intracytoplasmic globules and extracellular crystals revealed that the fringe of each globule and crystal had no limiting membrane and showed the same level of electron density. These findings suggest that the characteristic crystals in this tumor may have originated from the globules that were emitted from the carcinoma cells after their death as a result of saturation with intracytoplasmic globules.     

Morphogenesis of Michaelis-Gutmann bodies in cerebral malacoplakia. An ultrastructural study

Malacoplakia was found in the brain biopsy specimen from the wall of a cystic lesion in a 4-month-old girl. Ultrastructural study of the Michaelis-Gutmann bodies revealed that the initial stage of calcification appeared to be the deposit of needle-shaped apatite crystals within intracytoplasmic membrane-bound vesicles of histiocytes. Accumulation of apatite crystals and coalescense of calcified vesicles resulted in the formation of large laminated calcospherules. Extracellular Michaelis-Gutmann bodies and apatite crystal-containing matrix vesicles were also noted. Calcified vesicles and the Michaelis-Gutmann bodies were not observed in the phagolysosomes. Bacteria and viral particles were not identified. These findings suggest that matrix and intracytoplasmic membrane-bound vesicles play an important role in the initial stage of the formation of Michaelis-Gutmann bodies and that a mechanism other than bacterial or viral infection may be involved in cerebral malacoplakia.     

Calcification in human breast carcinomas: ultrastructural observations.

Calcification in human breast carcinomas has been studied ultrastructurally. Multiple deposits of needle-shaped crystals intimately associated with electrondense material were observed among tumour cells. Similar deposits were present in intracytoplasmic lumina and the adjacent stroma. Cytoplasmic calcification was seen in membrane-bound vesicles and as partially membrane-bound clusters of crystals. It is suggested that the calcification is the result of an active secretory process rather than calcified necrotic or degenerate tumour cells. The possible mechanisms of calcification are discussed. Both electron diffraction and electron probe analysis show that the crystaline material is hydroxyapatite.     

Crystals and Alpha-1-Antitrypsin-Reactive Globoid Inclusions in an Islet Cell Tumor of the Pancreas

An islet cell tumor of the pancreas with unusual light microscopic, ultrastructural, and immunocyto-chemical features is reported. In addition to secretory granules and positive immunostaining for pancreatic polypeptide, the tumor contained globoid intracytoplasmic inclusions by light and electron microscopy, which correlated with a positive immunoreaction for alpha-1-antitrypsin, and Reinkelike crystals.     

Intracytoplasmic immunoglobulin crystals in follicular lymphoma

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.     

Alveolar soft-part sarcoma in the uterine cervix

We describe a case of an alveolar soft-part sarcoma of the cervix in a 35-year-old woman. The light- and electron-microscopic and immunohistochemical findings are described. Periodic acid-Schiff-positive, diastase resistant, intracytoplasmic crystals, pathognomonic for alveolar soft-part sarcoma, were present. The cells expressed immunoreactivity for neuron-specific enolase and protein S100. The results of our own immunohistochemical examinations and those presented in the literature are discussed.     

Primary alveolar soft part sarcoma of the lung

Alveolar soft part sarcoma (ASPS) is a rare epithelial-like soft tissue sarcoma. The two main sites of its occurrence are the lower extremities in adults and the head and neck in children. Primary pulmonary involvement of this sarcoma, without evidence of soft tissue tumor elsewhere, is very exceptional. We present a case of primary ASPS of the lung in a 42-yr-old woman. A computed tomographic scan of the thorax demonstrated a well-circumscribed, solid tumor located in the right upper lobe. The mass was resected by right upper lobectomy. After 5 months, three metastatic lesions, involving lumbar vertebrae and occipital scalp, were found. Histologically, the tumor consisted of alveolar nests of large polygonal tumor cells, the cytoplasm of which frequently revealed periodic acid-Schiff-positive, diastase-resistant intracytoplasmic rod-like structures. On immunohistochemical staining, the tumor cells were positive only for vimentin and alpha-smooth muscle actin. Ultrastructural study using electron microscopy revealed characteristic electron-dense, rhomboid intracytoplasmic crystals.     

Malignant mesothelioma with intracytoplasmic crystalline inclusions

A 60-year-old female presented with a history of hoarseness, cough, chest pain, and dyspnea and a needle biopsy sample was submitted for histology. Light microscopy showed sheets of tumor cells with eosinophilic cytoplasm containing multiple crystals and eccentrically located nuclei. Electron microscopy showed large intracytoplasmic crystalloid inclusions. No crystalloid structures were found extracellularly. The tumor cells also had long slender microvilli and cell junctions, the features being consistent with a malignant epithelial mesothelioma. In the authors' experience this is a rare finding. The clinical information initially received was poor and electron microscopy was essential in making the correct diagnosis.     

Clinical, biochemical, and pathological features in a patient with plasma cell dyscrasia and Fanconi syndrome

Multiple myeloma is associated with a wide array of renal diseases that include myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, amyloidosis, cryoglobulinemia, tubular dysfunction, pyelonephritis, nephrocalcinosis, urate nephropathy, and infiltration by atypical plasma cells (or myeloma cells). Filtered immunoglobulin light chains may affect both the distal and, more frequently, the proximal tubule. Tubular abnormalities in patients with plasma cell dyscrasia may be more frequent than previously thought. A patient with a plasma cell dyscrasia is described, who presented with biochemical features consistent with Fanconi syndrome. Immunoelectron microscopy performed on the renal biopsy confirmed the presence of kappa light chain immunoglobulin in intracytoplasmic crystals in proximal tubular epithelial cells. This report is one of a few demonstrating the presence of light-chain immunoglobulin in intratubular crystals in a human renal biopsy obtained from a patient with a plasma cell dyscrasia and Fanconi syndrome.     

Clinical,Biochemical, and Pathological Features in a Patient with Plasma Cell Dyscrasia and Fanconi Syndrome

Multiple myeloma is associated with a wide array of renal diseases that include myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, amyloidosis, cryoglobulinemia, tubular dysfunction, pyelonephritis, nephrocalcinosis, urate nephropathy, and infiltration by atypical plasma cells (or myeloma cells). Filtered immunoglobulin light chains may affect both the distal and, more frequently, the proximal tubule. Tubular abnormalities in patients with plasma cell dyscrasia may be more frequent than previously thought. A patient with a plasma cell dyscrasia is described, who presented with biochemical features consistent with Fanconi syndrome. Immunoelectron microscopy performed on the renal biopsy confirmed the presence of kappa light chain immunoglobulin in intracytoplasmic crystals in proximal tubular epithelial cells. This report is one of a few demonstrating the presence of light-chain immunoglobulin in intratubular crystals in a human renal biopsy obtained from a patient with a plasma cell dyscrasia and Fanconi syndrome.     

Corneal and conjunctival crystals in paraproteinemia

A 64-year-old woman with bilateral corneal and conjunctival crystal deposition was evaluated. A biopsy of her conjunctiva showed intracytoplasmic inclusions of immunoglobulin crystals in fibrocytes, macrophages, and endothelial cells. Serum protein electrophoresis showed elevated kappa and IgA light and heavy chains which corresponded with immunoperoxidase staining results of the conjunctival biopsy. Conjunctival and corneal crystal deposition may be indicative of paraproteinemia, and histopathologic examination of a conjunctival biopsy may be useful in diagnosing this condition.     

Mechanism of formation of the psammoma bodies in serous adenocarcinomas of the ovaries]

Histological and electron microscopic examinations of 7 serous adenocarcinomas of the ovaries permitted to follow all the stages of psammous body formation starting from the submicroscopic level. The formation of psammous bodies was shown to be connected with a relatively differentiated epithelium of the adenocarcinomas. Initially, microcrystals of oxyapatites are deposed on accumulations of protein substances in ergastoplasm cysterns and on mitochondrial cristae. With further accumulation of these crystals relatively large intracytoplasmic inclusions of oxyapatites are formed which after confluence fill the cell which results in its death. In this way a small psammous body becomes free-lying.     

Observations on the formation of michaelis-gutmann bodies

An electron microscopic study of intracytoplasmic calcospherules (Michaelis-Gutmann bodies) in a case of renal malacoplakia revealed the following sequence of events in their development: formation of microcrystals of calcium apatite in phagolysosomes of the Hansemann macrophages, aggregation of the crystals to form an electron dense spherical body within the center of the phagolysosome, secondary peripheral microcrystal precipitation around the central sphere to produce the target shaped structure, and further peripheral calcification with obliteration of the phagolysosome itself. These changes explain various forms of calcospherules seen by light microscopy.     

IgA and IgM cytoplastic inclusions in a series of cases of chronic lymphocytic leukaemia.

Seventy-two cases of typical chronic lymphocytic leukaemia were screened by electron microscopy for the presence of intracytoplasmic immunoglobulin crystals. Immunoglobulin inclusions were found in four cases. Immunofluorescent studies showed that the inclusions contained IgA in two cases and IgM in the other two patients. Lambda light chain specificity was demonstrated in all four cases. The ultrastructure of the inclusions was identical in each patient except that in one of the IgA cases the inclusions were found in the perinuclear cistern in addition to the more usual location within cisternae of rough endoplasmic reticulum. Surface immunofluorescence showed mu heavy chains in the two cases displaying IgM crystal formation, but in the two IgA patients, no alpha heavy chains were demonstrable at the cell surface. The possible significance of these findings is discussed in relation to the existing literature.     

Ultrastructural and enzyme histochemical study of ovarian hilar cells in women and their relationships with sympathetic nerves

The ultrastructure of normal ovarian hilar cells, both during the reproductive era and after the menopause, shows evidence of steroid hormone synthesis. In this respect these cells are very similar to Leydig cells in that they contain mitochondria with a dense matrix, a highly developed smooth endoplasmic reticulum, Reinke crystals, and microcystalline inclusions. The latter are much more numerous than in the normal testis. Their enzymatic activities are quite similar to those of Leydig cells. Ovarian hilar cells seem to originate from progressive metamorphosis of fibroblastic cells under the induction of sympathetic nervous structures. Their relations with hilar nerves are of three types: simple direct membrane contact without a Schwann cell sheath, intimate intracytoplasmic relationships, and specialized contacts, which are comparable to a synapse.     

Intracytoplasmic inclusions (including the so-called “rhabdoid” phenotype) in pancreatic endocrine tumors

The cytoplasm of pancreatic endocrine tumors (PET) can show a diverse range of appearances from clear, to oncocytic, to intracellular mucin accumulation, and the presence of intracytoplasmic inclusions. Intracytoplasmic eosinophilic inclusions can vary morphologically and the spectrum ranges from small, dot-like hyaline inclusions, to deeply acidophilic/eosinophilic ones that occupy almost the whole cytoplasm and displace the nucleus eccentrically: the so-called “rhabdoid” phenotype. The aim of this study was to analyze the frequency, morphology, behavior, and relationship to clinicopathological features of large intracytoplasmic inclusions, including the rhabdoid phenotype, in a large number of PET. The morphological features of 84 cases were assessed for the presence of large, globular intracytoplasmic inclusions. Fourteen of 84 cases contained intracytoplasmic inclusions with 5 cases containing cells conforming to the characteristic rhabdoid morphology. The remaining nine cases showed pale intracytoplasmic inclusions. Four of the five cases with rhabdoid cells had spread to lymph nodes and/or peripancreatic fatty tissue. This study confirms that a spectrum of large intracytoplasmic inclusions is encountered in PET, ranging from lightly eosinophilic intracytoplasmic globules to the more typical rhabdoid phenotype (deeply eosinophilic inclusions). This phenotype, in particular the rhabdoid cells, is worthy of attention as a proportion may show lymphovascular invasion with evidence of metastasis at the time of presentation, irrespective of size, mitotic rates, or necrosis.     

Intracytoplasmic inclusions (including the so-called "rhabdoid" phenotype) in pancreatic endocrine tumors

The cytoplasm of pancreatic endocrine tumors (PET) can show a diverse range of appearances from clear, to oncocytic, to intracellular mucin accumulation, and the presence of intracytoplasmic inclusions. Intracytoplasmic eosinophilic inclusions can vary morphologically and the spectrum ranges from small, dot-like hyaline inclusions, to deeply acidophilic/eosinophilic ones that occupy almost the whole cytoplasm and displace the nucleus eccentrically: the so-called "rhabdoid" phenotype. The aim of this study was to analyze the frequency, morphology, behavior, and relationship to clinicopathological features of large intracytoplasmic inclusions, including the rhabdoid phenotype, in a large number of PET. The morphological features of 84 cases were assessed for the presence of large, globular intracytoplasmic inclusions. Fourteen of 84 cases contained intracytoplasmic inclusions with 5 cases containing cells conforming to the characteristic rhabdoid morphology. The remaining nine cases showed pale intracytoplasmic inclusions. Four of the five cases with rhabdoid cells had spread to lymph nodes and/or peripancreatic fatty tissue. This study confirms that a spectrum of large intracytoplasmic inclusions is encountered in PET, ranging from lightly eosinophilic intracytoplasmic globules to the more typical rhabdoid phenotype (deeply eosinophilic inclusions). This phenotype, in particular the rhabdoid cells, is worthy of attention as a proportion may show lymphovascular invasion with evidence of metastasis at the time of presentation, irrespective of size, mitotic rates, or necrosis.