Multinucleated Histiocytes Research Articles

Granulomatous prostatitis: A spectrum including nonspecific, infectious, and spindle cell lesions

Most granulomas of the prostate are nonspecific; infectious, post-operative, and allergic lesions are much less common. Fine-needle aspiration findings in the typical case are distinctive and easily recognized. Several series have been reported, but few have included histologic follow-up. We describe three cases of granulomatous prostatitis (GP) which showed a spectrum of findings confirmed by histologic sections. In all cases, carcinoma was suspected clinically. Case 1 represents typical nonspecific GP with epithelioid and multinucleated histiocytes. In case 2, aggregates of epithelioid histiocytes alternated with areas of necrosis and neutrophils. Histologically, the granulomas showed purulent centers. Silver stains revealed budding yeast in smears and sections. Cultures of FNA material subsequently revealed Cryptococcus. In case 3, the histiocytes were predominantly spindled and occurred singly and in groups. The differential diagnosis included reactive and neoplastic spindle cell lesions. Histologic sections showed GP with spindled histiocytes. Appreciation of the broad cytologic spectrum of GP will facilitate accurate cytologic diagnosis.

Radiation changes in endocervical cells in brush specimens

Although the cytologic changes in cervical and vaginal squamous cells after radiation therapy were well-described decades ago, alterations in endocervical cells in response to radiation therapy have not been delineated in detail. We studied the effect of radiation therapy (usually combined linear accelerator beam and radium insertion) on endocervical cells as seen in endocervical brush specimens from 24 patients treated for cervical cancer. Of the 40 smears examined, 45% were taken 3-6 mo after the completion of radiotherapy, 28% at 10-14 mo, and 20% at 18-34 mo. Endocervical cells appeared as single cells and in clusters and had lavender, mucin-filled cytoplasm. When present in clusters, they lacked the honeycomb appearance of normal endocervical cells. In smears taken at 3-6 mo, the majority of endocervical cells were enlarged (100% of smears) but they usually had normal nuclear/cytoplasmic ratios. Their nuclei were enlarged (100% of smears); varied in size (100%); had some coarse chromatin (67%) and large nucleoli (78%); and were multinucleated (89%). Repair cells and multinucleated histiocytes were seen in 83% and 61% of smears, respectively. Each of these cytologic findings was less apparent in follow-up smears taken more than 6 mo after the completion of radiation therapy. Awareness of these cytologic changes in endocervical cells after radiation therapy precludes the overdiagnosis of cancer in follow-up endocervical brush specimens.

Significance of giant cells in fine-needle aspiration biopsies of benign and malignant lesions of the pancreas.

The cytologic results of 44 consecutive fine-needle aspiration (FNA) biopsies of the pancreas are reported. The series consisted of 27 women and 17 men with an age range of 31-89 yr (mean, 61.5). Excluding insufficient cases, the sensitivity of the procedure was 88%, specificity was 100%, positive predicative value (PV) was 100%, negative PV was 69%, and efficiency of the test was 90%. There were 29 true-positive, four false-negative, and nine true-negative diagnoses. Two specimens were insufficient for diagnosis. Giant cells of varying types were seen in both the malignant and benign cases. Two of the benign cases demonstrated rare multinucleated foreign body-type giant cells, most likely representing the changes seen in pancreatitis. In 13 malignant cases, multinucleated tumor cells were present, while six additional cases had multinucleated benign histiocytes reflecting the associated pancreatitis. Two malignant cases each had tumor giant cells and benign multinucleated histiocytes. Three of the malignant cases had numerous multinucleated tumor giant cells arranged in a dissociative fashion with evidence of cytophagocytosis consistent with a pleomorphic giant-cell carcinoma of the pancreas. One additional case demonstrated numerous multinucleated osteoclastic-like cells consistent with an osteoclastic tumor of the pancreas. This article documents the accuracy of FNA biopsy of the pancreas and notes that giant cells of varying types can be found in pancreatic FNA biopsies. Appreciation of the various types of giant cells in pancreatic FNA biopsy is important for diagnostic accuracy and prognosis.

Oxalate Bone Disease - an Emerging Form of Renal Osteodystrophy

Rosette-like arrays of highly birefringent calcium oxalate crystals are commonly seen in the marrow space of bone biopsy specimens taken from patients with primary hyperoxaluria, particularly if complicated by renal failure. Similar deposits have been described in chronic hemodialysis patients with secondary forms of oxalosis. Large multinucleated histiocytes may be seen surrounding these crystal deposits. Many of these cells are histologically indistinguishable from osteoclasts. We present a patient in whom this histiocytic reaction appeared to be of sufficient magnitude to stimulate bone resorption and to cause severe osteodystrophy. This observation, and those of other investigators reviewed in the discussion, suggest that oxalate deposition within bone may contribute to the pathogenesis of uremic osteodystrophy in chronic renal failure patients with primary or secondary types of oxalosis.

ｔｗｙマウスにおける石灰沈着性けん炎

A morphological and biochemical study of calcifying tendinitis in twy mouse was carried out. Calcification of the aponeurosis plantaris was first observed at the 7th week of age. Thereafter multinucleated giant cells and histiocytes were seen around the calcium deposits. Infiltration of polymorphonuclear leukocytes followed. These inflammatory cell reaction confined to the tendon. Then, proliferation of capillaries and fibroblasts was observed, and lacunar formation around the calcium deposits was sometimes observed. In later stage, inflammatory cell infiltration subsided, and fibrous scar and calcium deposits were recognized in the tendon. Deposition of hydroxyapatite was confirmed in the tendon by X-ray powder analysis.These changes resemble those of man, and calcifying tendinitis in twy mouse is thought to be a valuable model of the corresponding disease in man.

Pulmonary Vascular Talc Granulomatosis

A 37-year-old physician who had multiple intestinal resections for complications of Crohn's disease developed disseminated malignant melanoma following excision of a primary cutaneous melanoma. He required long-term parenteral nutrition via a subclavian catheter because of the Crohn's disease and a surgically shortened bowel with multiple fistulas. Metastatic melanoma and episodes of partial intestinal obstruction caused recurrent pain, necessitating analgesic medication. The patient was known to self-administer pulverized meperidine hydrochloride (Demerol) tablets in suspension via his indwelling venous catheter over a period of several months prior to his death. At autopsy extensive deposits of metastatic melanoma were found in the gastrointestinal tract, heart, lungs, liver, and lymph nodes. The lungs demonstrated acute pulmonary edema. Microscopy showed widespread intravascular and perivascular foreign-body granulomas involving small pulmonary arterioles. These were composed of multinucleated giant cells and histiocytes with variable fibrosis, incorporating numerous yellowish refractile crystals having an elongated, needlelike, or rhomboidal shape. The

Pulmonary vascular talc granulomatosis

A 37-year-old physician who had multiple intestinal resections for complications of Crohn's disease developed disseminated malignant melanoma following excision of a primary cutaneous melanoma. He required long-term parenteral nutrition via a subclavian catheter because of the Crohn's disease and a surgically shortened bowel with multiple fistulas. Metastatic melanoma and episodes of partial intestinal obstruction caused recurrent pain, necessitating analgesic medication. The patient was known to self-administer pulverized meperidine hydrochloride (Demerol) tablets in suspension via his indwelling venous catheter over a period of several months prior to his death. At autopsy extensive deposits of metastatic melanoma were found in the gastrointestinal tract, heart, lungs, liver, and lymph nodes. The lungs demonstrated acute pulmonary edema. Microscopy showed widespread intravascular and perivascular foreign-body granulomas involving small pulmonary arterioles. These were composed of multinucleated giant cells and histiocytes with variable fibrosis, incorporating numerous yellowish refractile crystals having an elongated, needlelike, or rhomboidal shape. The

Intraoperative cytology of osseous lesions.

Cytologic preparations were made from 53 biopsies of osseous and related lesions submitted for intraoperative diagnosis. Smears made by scraping the surface of the lesion and spreading the material obtained on a glass slide were most commonly used. These preparations were found to be valuable adjuncts to frozen sections because cytologic details were so much more clearly visible. Among specific diagnostic features found to be particularly helpful were the large numbers of nuclei found in most of the multinucleated cells from giant-cell tumors but in few osteoclasts from other lesions; the metachromatic staining of osteoid in air-dried, Romanowsky-stained smears from osteosarcomas; and the ease with which multinucleated cells can be identified in smears from chondrosarcomas. The characteristic appearance of chondroblasts from a chondroblastoma; the distinctive appearances of osteoclasts and multinucleated histiocytes from eosinophilic granulomas; the unique appearance of synovial cells from pigmented synovitis; and the ease with which small cells of a metastatic carcinoma could be distinguished from hematopoietic bone-marrow cells were other significant findings. These and other features of the lesions encountered are presented in greater detail.

The validity of Pap smear parameters as predictors of endometrial pathology in menopausal women.

Cytopathologists recognize that certain Pap smear findings are suspicious for endometrial pathology in menopausal women. To study their prognostic importance in the directed cervical smear, six parameters were used to evaluate smears for evidence of an endometrial lesion: the presence of (1) histiocytes, (2) multinucleated histiocytes, (3) nonspecific inflammation, (4) bleeding, (5) elevated squamous cell maturation index, and (6) the degree of cytologic atypicality of endometrial glandular cells, expressed as a "score" from 0 to 6. Clinical pathologic correlation of 102 women with these parameters was undertaken. A multivariable statistical analysis determined which of these six parameters was most predictive of an endometrial lesion. Cytologically "scored" endometrial glandular cells was the only parameter predictive of endometrial pathology. Its emergence as the sole prognostic cervical Pap smear parameter for endometrial pathology has not been previously reported. This predictive value was consistent even with control for bleeding history and age. Appropriate interpretation of abnormal Pap smear findings contributes substantial diagnostic information in the evaluation of the endometrium.

Granulomatous inflammation of the heart.

Morphologic characteristics of granulomatous inflammation in the heart and pericardium are discussed. In rheumatic fever, two types of myocardial lesion are present--a nonspecific myocarditis and a specific lesion characterized by granulomas known as Aschoff's nodules. The latter undergo a cycle of development and resolution; in their mature stage, they contain Aschoff's cells which are uni- or multinucleated histiocytes with a serrated nuclear chromatin bar. Ultrastructural studies do not suggest a relationship between these cells and cardiac or smooth muscle cells. In metabolic disorders, granulomas occur in Farber's disease (lipogranulomatosis), gout (in which tophi are associated with calcific deposits and with a foreign body cellular reaction), the various syndromes of oxalosis (in which oxalate deposits also lead to a foreign body reaction), and in chronic granulomatous disease of childhood. Foreign body giant-cells can also be found in association with calcification of necrotic myocytes and in the syndromes of "cholesterol pericarditis." Well-developed granulomas occur in sarcoidosis, giant cell myocarditis, as a reaction to foreign bodies and devices implanted within the cardiovascular system, and in certain diseased caused by infective agents (tuberculosis, fungal and parasitic disorders). Infiltration of the heart by nongranulomatous masses of histiocytes can occur in Whipple's disease, Niemann-Pick disease, the hyperlipoproteinemias, Gaucher's disease, and in proliferative disorders of the mononuclear phagocyte system (juvenile xanthogranuloma, Chester-Erdheim syndrome, and malignant histiocytosis).

Diphenylhydantoin-induced hypersensitivity reaction with interstitial nephritis

A 10-year-old black girl had an episode of diphenylhydantoin(DPH)-induced exfoliative dermatitis, lymphadenopathy, hepatitis, peripheral eosinophilia, and transient renal failure. The findings of specific lymphocyte sensitization of DPH, a clinically typical delayed hypersensitivity reaction, multinucleated histiocytes in the renal interstitium, and negative renal immunofluorescence studies for immune reactants indicate that the child's renal injury was at least partially cell-mediated.

THE EFFECTS OF PROPIONIC ACIDEMIA ON HEMATOPOIESIS

We evaluated hematopoiesis in a 1 month-old infant with propionic acidemia who presented with pancytopenia. Her bone marrow (BM) showed dysmyelopoiesis and maturation arrest of all cell lines. Numerous mono- and multinucleated histiocytes engaged in hemophagocytosis were present. We studied the effects of the child's serum and of propionic acid (PA, pH 7.3) on mouse BM colony forming units-erythroid (CFU-E) and colony forming units-granulocytic-monocytic (CFU-GM) grown in fibrin clots. The patient's (pt's) serum significantly inhibited CFU-E but not CFU-GM compared to normal human sera. PA inhibited growth of CFU-E and CFU-GM as shown in the table. Semi-soft agar culture of human BM CFU-GM showed complete inhibition with 5 mM PA but none with 1 mM or 0.5 mM PA. There was no consistent inhibition of mouse or human BM cultures by glycine, tiglic acid, or 3-OH PA (1.0, 0.1, 0.01 mM, pH 7.3), all of which were elevated in this child. From these results we conclude that the pancytopenia and hematologic abnormalities found in this infant may be directly related to the effects of propionic acid.

Asteroid bodies in fibrocystic mastopathy

An unusual microscopic feature of a case of fibrocystic mastopathy is reported. Among the chronic inflammatory cells within the mammary stroma were scattered multinucleated histiocytes, some of which contained asteroid bodies. The patient showed no evidence of sarcoidosis.

So-called histiocytosis X and malignant histiocytosis

A retrospective study of 12 cases of so called histiocytosis-X and 3 cases of malignant histiocytosis was done. It was possible to establish the differences in clinical, morphologic and cytochemical findings of both diseases. The diagnosis of histiocytosis-X can be confirmed by multinucleated histiocytes interrupted by eosinophils and plasmacells. The histopathology of malignant histiocytosis is different and is characterized by atypical histiocytes. Erythrophagocytosis throughout the tissues is seen. Typical histochemistry (acid phosphatase and naphtol-AS-acetat-esterase) findings are also helpful for diagnosis. The treatment of both diseases should be continued at least six months after disappearance of clinical apparent lesions. Combination chemotherapy with vinblastine and prednisone is suggested. In cases of histiocytosis-X in isolated lesions curettage or irradiation may be adequate. Long term remissions and presumed cures of histiocytosis-X are possible in over 70% of the cases. A strict correlation between the prognosis and the degree of involvement is confirmed. Even in cases of malignant histiocytosis, previously reported as rapidly fatal disease, combination chemotherapy may produce complete long term remissions.

Malignant fibrous histiocytoma of bone: A chnico-pathological and electronmicroscopical study

The clinicopathological and ultrastructural features of seven Malignant Fibrous Histiocytomas reported to the Spanish Registry of Bone Tumors were studied. Two patients were females (20 and 60 years old) and the other five males (15, 37, 67, 38 and 17 years old). The tumors were located in the lower femur (3 cases), upper tibia, upper humerus, rib and iliac bone. The past medical history revealed previous fracture in one patient and previous radiation of the affected bone in another; in a third patient the tumor associated to a bone infarct. Microscopically all tumors presented a storiform pattern composed of neoplastic fibroblasts, histiocytes, and malignant multinucleated giant cells. There was no evidence of osteoid or bone tissue formation by the tumor cells. Five cases were studied with electronmicroscopy; the tumor cells had features of fibroblasts, myofibroblasts, histiocytes and multinucleated histiocytes. Primary and secondary lysosomes, along with lipid vacuoles were common findings in the tumor cells. The value of the electron-microscopy in the differential diagnosis of this tumor is emphasized.

Primary reticulosis of the central nervous system

On the basis of a study carried out on 9 cases of their own and of published data, the authors show that the pathological processes involving the cerebral reticulohistiocytic system (processes due to proliferation of the periadventitial reticular cell and its different forms, usually giving lesions predominantly localized around the ventricular cavities) may be classified as follows: 1. (1) Inflammatory reticuloendotheliosis—encephalitis of the Cervos-Navarro type, developing around the vessels where lymphocytes and reticular cells, plasma cells, histiocytes and microglia (argyrophilic elements) can be seen. 2. (2) Proliferative reticuloendotheliosis. The gross examination shows periventricular tumour formation. Microscopic examination shows proliferation of reticular elements, histiocytes and giant multinucleated histiocytes with countless mitoses. Silver staining reveals non-argyrophilic alongside argyrophilic cells (histiocytes and microglia). 3. (3) Cerebral reticulosarcomatosis; this includes a non-differentiated and a differentiated form in which appearances of neoplasia are mixed with inflammatory granulomatous charges (reticulohistio-microgliomatosis).