Multinucleated Histiocytes Research Articles

A reticular variant of elastolytic giant cell granuloma.

An 80-year-old man presented with a distinctive reticular form of elastolytic giant cell granuloma (EGCG). This represents a rare subset of EGCG, thus belonging to a larger group of granulomatous skin diseases with poorly understood pathogenesis. The patient exhibited numerous erythematous to brownish, sharply demarcated patches of reticulate appearance with partial central atrophy and nonelevated margins, which involved the trunk and especially chest, shoulders, upper back and arms. Skin biopsy revealed a granulomatous infiltrate with multinucleate histiocytes containing remnants of elastic fibres in conjunction with a significant loss of elastic fibres throughout the dermis. There is little published information on treatment, which remains unsatisfactory.

Regional Metastases, Artifacts, and Mimics in Axillary Lymph Nodes

Axillary lymph node status is an important prognostic factor in breast cancer. In most patients, sentinel lymph node biopsy has replaced axillary dissection because it decreases morbidity and permits accurate staging and local control. The increased histologic scrutiny of sentinel lymph nodes and consideration of drainage phenomena has led to a heightened awareness and detection of previously described but rare findings. These include false-positive findings such as benign heterotopic glands, transported epithelial cells, nevus cell aggregates, megakaryocytes, multinucleated giant cells, silicone lymphadenopathy, and histiocytes, all of which may mimic metastatic carcinoma. Conversely, degenerated or treated cancer cells can appear artifactually negative, mimicking histiocytes. In addition, many artifactual changes in lymph nodes are due to the use of immunohistochemistry. Overlapping staining with dendritic cells, histiocytes, and plasma cells can be misinterpreted as positive. Most of these issues can be resolved by comparing the lymph node findings with the primary tumor.

Granulomatous Lymphangiitis (Melkersson‐Rosenthal Type)

A 33‐year‐old Caucasian female presented with a ten‐year history of flushing and facial swelling partially responsive to anti‐inflammatory and anti‐microbial therapies. Progressive edema of the right upper eyelid was recently treated by blepharoplasty. The blepharoplasty specimen had a dense mononuclear inflammatory infiltrate and diffuse non‐caseating granulomas composed of epithelioid and multinucleated histiocytes. The granulomas appeared both peri‐and intralymphatic with prominent molding. Special stains and polarization studies were negative. To confirm the intralymphatic location of these granulomas we performed immunohistochemical staining with Factor VIII and D2–40. D2–40 is a new monoclonal antibody that reacts with an O‐linked sialoglycoprotein found on lymphatic endothelium, fetal testis, and on the surface of testicular germ cell tumors. In recent studies, clone D2–40 has shown staining in lymphatic channel endothelium but not in adjacent capillary. Factor VIII antibody highlighted both lymphatic and blood vessel endothelium, while D2–40 stained only the lymphatic endothelium and confirmed the intra‐lymphatic location of granulomas. The patient was diagnosed with granulomatous lymphangiitis of the Melkersson‐Rosenthal type (orofacial granulomatosis). Granulomatous lymphangiitis is characteristic but not completely diagnostic of the Melkersson‐Rosenthal syndrome. We present the complex differential diagnosis of intralymphatic granulomas and the use of a new monoclonal antibody helpful in verifying their location.

Histological analysis and biological effects of granulation tissue around loosened hip prostheses in the development of osteolysis

Although aseptic loosening of the prosthesis is a long-term complication after total joint replacement, the detailed mechanism of osteolysis remains unknown. We examined 82 samples from 40 patients with aseptic loosened hip prostheses histologically, and compared the distribution of particles, macrophages/histiocytes, and foreign body giant cells in the retrieved tissue from capsules and around prostheses. Furthermore, to investigate the mechanism of osteolysis, we cultured tissue from a patient with massive osteolysis and examined the effects of the conditioned medium on osteoblasts in vitro. Numerous multinucleated giant cells and histiocytes were present, and polyethylene particles ranging from medium to large were identified in the polarized light. However, the distribution was heterogeneous, and no particles were found microscopically in about 30%–40% of periprosthetic tissues, and in 60% of capsules. The amount of particles correlated with giant cells, but not with histiocytes. The conditioned medium of the granulation tissue culture stimulated osteoblasts to produce interleukin-6 in both protein and mRNA, and this was in part inhibited by anti-tumor necrosis factor-α or the interleukin-1β antibody, suggesting that interleukin-6 production is mediated by several cytokines. These findings suggest that interleukin-6, which is produced not only by macrophages but also by osteoblasts, is a contributing factor to aseptic loosening.

Keratinized Squamous Cells in Fine Needle Aspiration of the Brain

To analyze the differential diagnosis when keratinized squamous cells are found in a brain aspirate. Twenty cases of brain aspirates with keratinized squamous cells were retrieved (1982-2001). Diagnoses included craniopharyngioma (CP) (n = 11), metastatic squamous cell carcinoma (SCC) (n = 5), epidermoid cyst (EC) (n = 3) and Rathke cleft cyst (RCC) (n = 1). Aspirates were obtained under stereotactic radiologic (CT) guidance. Smears were stained with Diff-Quik or Papanicolaou stain, and cell block sections were stained with hematoxylin and eosin. Radiologic and histopathologic correlation with subsequent resection specimens was performed in selected cases. CP showed cellular smears with numerous keratinized squamous cells in a background of degenerated cellular and keratinaceous debris. Also noted were clusters of anucleate squamous cells, multinucleated giant cells, histiocytes, calcified debris and characteristic fragments of basaloid epithelial cells. Metastatic SCC showed single cells and tissue fragments of markedly atypical and focally keratinized cells with enlarged, hyperchromatic nuclei; prominent pleomorphism in a background of necrotic cellular debris and acute inflammatory exudate. EC showed numerous isolated keratinized squamous cells often with prominent keratohyaline granules and occasional parakeratotic cells in a relatively clean background. RCC showed single cells and aggregates of benign-appearing squamous cells admixed with numerous anucleate squames and hemosiderin-laden macrophages. Glandular-type epithelium was present only rarely. Squamous cell-containing lesions in the brain present a spectrum of pathologic entities. Although they all display the common morphologic denominator of keratinizing squamous cells, subtle cytomorphologic differences exist in these lesions, permitting an accurate cytopathologic diagnosis. Clinicardiologic features and anatomic location of the tumor in the brain are additionally helpful.

Multiple hypoechoic lesions in bilateral testes

A31-year-old man was referred with a chief complaint of a palpable painless nodule in his right testis. An ultrasound examination revealed multiple, well-defined, hypoechoic lesions in both testes 1 Salmeron I. Ramirez-Escobar M.A. Puertas F. et al. Granulomatous epididymo-orchitis sonographic features and clinical outcome in brucellosis, tuberculosis and idiopathic granulomatous epididymo-orchitis. J Urol. 1998; 159: 1954-1957 Abstract Full Text Full Text PDF Scopus (45) Google Scholar (Fig. 1). T1-weighted magnetic resonance imaging showed multiple areas of high-intensity signal, 3 to 10 mm in diameter, and T2-weighted magnetic resonance imaging showed low-intensity signal in these nodules 2 Senzaki H. Watanabe H. Ishigure Y. A case of very rare tuberculosis of the testis. Jpn J Urol. 2001; 92: 534-537 Google Scholar (Fig. 2). The head of the right epididymis was slightly dilated. Because the patient’s father had been hospitalized for pulmonary tuberculosis when the patient was 15 years old, he underwent a workup for tuberculosis. However, chest radiography and computed tomography were nondiagnostic, and culture and polymerase chain reaction failed to reveal Mycobacterium tuberculosis in his sputum. Serum markers for testicular cancer and malignant lymphoma and serum anti-syphilis antibody were negative. He underwent exploration of the right scrotal contents. One nodule in the testicular parenchyma removed under an operating microscope proved to be a tuberculoma with multinucleated histiocytes and caseous necrosis. The patient had been treated with rifampicin, isoniazid, ethambutol, and pyrazinamide for 1 year at the latest follow-up visit, and the nodules had become smaller bilaterally. Although tuberculosis of the testis is rare, we may encounter this disease as the prevalence of acquired immunodeficiency syndrome with treatment-resistant tuberculosis increases. 3 Kumar P. Shishikala P. Chandrashekar H.R. et al. Acquired immunodeficiency syndrome presenting as testicular tuberculosis. J Assoc Physicians India. 2000; 48: 1111-1112 Google Scholar FIGURE 2Magnetic resonance imaging of right testis and epididymis (sagittal section). (a) T1-weighted magnetic resonance image showing multiple, well-defined mass lesions (3 to 10 mm in diameter) with high-intensity signals in testicular parenchyma (arrows). (b) T2-weighted magnetic resonance image showing low-signal intensity (arrowheads) of same lesions. Head of epididymis slightly enlarged. View Large Image Figure Viewer

Sialadenitis with Crystalloid Formation

To assess the utility of fine needle aspiration cytology in the diagnosis of sialadenitis with crystalloid formation. In 15 cases, salivary gland masses were aspirated using a disposable, 20-mL syringe and 25-gauge needles, maintaining negative pressure. Smears routinely were air dried and stained by Diff-Quik (Dade Behring AG, Düdingen, Germany). Occasionally smears were fixed in alcohol and stained by the Papanicolaou method. The smears showed large numbers of non-birefringent crystalloids of varying sizes and shapes. The crystalloids stained deep blue with Diff-Quik and bright orange with Papanicolaou stain. Multinucleated histiocytes, neutrophilic leukocytes and benign salivary gland parenchyma were found, also. Fine needle aspiration cytology provides an accurate diagnosis of sialadenitis with crystalloids and is useful for avoiding unnecessary surgery.

Indinavir-associated interstitial nephritis and urothelial inflammation: clinical and cytologic findings.

The objective of the present study was to characterize the genitourinary syndromes that accompany indinavir-associated pyuria. Of 23 indinavir-treated patients with persistent pyuria, 4 had isolated interstitial nephritis, 10 had both interstitial nephritis and urothelial inflammation, 7 had isolated urothelial inflammation, and 2 had pyuria with nonspecific urinary tract inflammation. A total of 21 patients had multinucleated histiocytes identified by cytologic testing of urine specimens. Urine abnormalities resolved in all 20 patients who stopped receiving indinavir therapy. Pyuria continued in the 3 patients who continued receiving indinavir. Six patients had elevated serum creatinine levels, which returned to baseline levels when indinavir was discontinued. In conclusion, indinavir-associated pyuria was frequently associated with evidence of interstitial nephritis and/or urothelial inflammation, multinucleated histiocytes were commonly present in urine specimens, and cessation of indinavir therapy was associated with prompt resolution of urine abnormalities.

Fournier Gangrene Associated With Crohn Disease

A 17-year-old boy presented with Fournier gangrene associated with previously undiagnosed Crohn ileocolitis. Fournier gangrene was managed by débridement, broad-spectrum antibiotics, and hyperbaric oxygen. A diverting ileostomy was performed before skin grafting and scrotal reconstruction. Microscopy of a full-layer surgical sample from the terminal ileum revealed granulomas with multinucleated histiocytes, consistent with Crohn disease. Crohn disease was treated with mesalamine, metronidazole, 6-mercaptopurine, and infliximab. The patient was discharged on hospital day 32. At 6-month follow-up, reconstruction of his scrotum had completely healed. Ostomy output was normal.

Incidental sampling of branchial remnants: A potential source of error in fine-needle aspiration of neck lesions—a case report

Remnants of the branchial apparatus can produce lesions in the head and neck region in later life, often amenable to fine-needle aspiration (FNA) diagnosis. Yet such remnants or rudimentary lesions can remain clinically undetected and can later interfere with the cytologic interpretation of other deep lesions of the neck, as the present case demonstrates. In this case the lesion, which by a subsequent resection turned out to be a neurilemmoma, had been adequately sampled by the FNA, yet the cytologic diagnosis was sidetracked by the presence in the specimen of immature squamous epithelial tissue fragments and other elements (multinucleated histiocytes, calcifications), on the basis of which the diagnosis of an epithelial lesion, likely malignant, was made. The neck surgery and a preceding endoscopic examination of the mouth, pharynx, and larynx did not identify such a lesion, but a detailed microscopic examination of the fibroadipose tissue between the tumor and the peripharyngeal region revealed the presence of epithelial microfragments with morphology partly corresponding to that of the FNA cytology, highly indicative of a branchiogenic lesion in the peripharyngeal region. The basic embryology of the branchial apparatus resulting in such defects is presented, as well as tentative guidelines for recognizing material deriving from accidental sampling of such lesions during FNA investigations of deep-seated masses of the neck. Diagn. Cytopathol. 2000;22:157–160. © 2000 Wiley-Liss, Inc.

Scalloped cell xanthogranuloma.

We describe nine cases of scalloped cell xanthogranuloma, a distinct solitary variant of non-Langerhans cell histiocytoses. In this retrospective clinicopathological study scalloped cell xanthogranuloma mostly occurred on the back or head and neck of young adult males diagnosed as a xanthogranuloma, naevus, or basal cell carcinoma. Histology characteristically revealed a sheet-like infiltrate of predominantly scalloped histiocytes (> 79% of all cell types) in the upper dermis. Other mononuclear (vacuolated, xanthomatized, spindle-shaped, oncocytic) and multinucleate (foreign body, ground glass and Touton) histiocytes were also regularly seen. Immunohistochemically, all cases exhibited a macrophage/dendritic cell lineage positive with KP1 (CD68), KiM1p, HAM 56 and factor XIIIa. Ultrastructurally, numerous intracytoplasmic dense, occasionally also myeloid bodies were present. No associated systemic disease, hyperlipidaemia or recurrence were seen during follow-up. These findings are similar to those of early lesions of xanthoma disseminatum: thus, scalloped cell xanthogranuloma could be regarded as a solitary counterpart of xanthoma disseminatum, and, moreover, fits neatly into a unifying concept of non-Langerhans cell histiocytoses.

Unusual expression of S-100 protein in histiocytic neoplasms.

Twenty-nine cases of histiocytic neoplasms, some resembling juvenile xanthogranuloma (JXG) and others resembling reticulohistiocytoma (RH), were evaluated. Immunohistochemical stains were performed. In this series, seven cases were identified that expressed S-100 protein positive cells. The S-100 positive cells were predominantly large mononuclear and multinucleated histiocytes with eosinophilic cytoplasm, but also in some cases xanthomatous cells and Touton giant cells. These cells also expressed a positive reaction for vimentin, KP-1, and Factor XIIIa. There was no reactivity observed for monoclonal antibody 010(CD1a). A positive reaction for S-100 protein is conventionally accepted as a useful differentiating feature between histiocytosis X and non-X histiocytosis such as JXG and RH. The conflicting results of the immunohistochemical stains in the lesions we studied could be potential pitfalls in diagnosing histiocytic neoplasms.

Giant Cell Arteritis Manifesting as Chronic Cough and Fever of Unknown Origin

A 57-year-old white man sought medical attention because of chronic cough and fever of unknown origin. An extensive work-up over 4 weeks, including repeated blood cultures, chest roentgenograms, a gallium scan, and computed tomographic scans of the sinuses, chest, and abdomen, was nondiagnostic. The patient was referred to our institution for bronchoscopy. Further analysis of his history revealed that he had a headache in conjunction with the cough and an episode of a flashing color design in his left eye 1 week before assessment. The erythrocyte sedimentation rate was 115 mm in 1 hour. A biopsy of the temporal artery showed granulomatous inflammation of the vessel wall with multinucleated giant cells, histiocytes, lymphocytes, plasma cells, and few eosinophils. The multinucleated giant cells were closely related to the fragmented elastic lamina. Corticosteroid therapy resulted in prompt resolution of the chronic cough and fever. Giant cell arteritis should be considered in the differential diagnosis of chronic cough.

Follicular variant of papillary carcinoma of the thyroid: fine-needle aspirates with histologic correlation.

Crile and Hazard reported in 1953 a follicular pattern of papillary thyroid carcinoma. Little has been said about this pattern in the cytologic literature. From more than 8,000 thyroid aspirates in our files, we reviewed all those diagnosed as "follicular variant of papillary carcinoma," "suspect follicular variant of papillary carcinoma," and "follicular neoplasm vs. follicular variant of papillary carcinoma." Also, we reviewed all aspirates in which a diagnosis of follicular variant of papillary carcinoma had been made on surgically excised glands, regardless of the cytologic diagnosis; 63 aspirates from 45 patients were collected. All smears were air-dried and stained with Diff-Quik. Most smears were very cellular ("tumor cellularity"), and the neoplastic follicular cells formed empty follicles, rosettes, tubules, and papillary structures. Nuclei were twice the size of red blood cells, had smooth contours, were hyperchromatic, and varied in shape but not much in size. Nuclear overlapping was common. Some nuclei had one small and almost pointed end, thereby resembling arrowheads. Intranuclear inclusions, multinucleated histiocytes, and psammoma bodies were uncommon. Pink-stained colloid was frequent.

Langerhans Cell Histiocytosis of Lymph Nodes: A Morphological Assessment of 43 Biopsies

The morphology of Langerhans cell histiocytosis (LCH) involving lymph nodes was analyzed in 43 biopsies from 39 patients and findings were correlated with clinical data. Five histological motifs were recognized: sinusoidal, limited sinusoidal, epithelioid granulomatous, partial effacement, and total effacement. Lesions were composed of histiocytes of the Langerhans cell (LC) family, macrophages, multinucleated giant histiocytes, T lymphocytes, and eosinophils in varying proportions. Proliferative fractions ranged from 2.6 to 48% and 2 of 25 specimens showed a hyperdiploid aneuploid DNA ploidy profile. Epithelioid granulomas composed of histiocytes with the LC phenotype dominated three abdominal specimens, reflecting a picture of LCH not previously reported. Total effacement seen in three patients, was associated with unmarked histiocytoid cells, high proliferative fraction, aneuploid DNA ploidy profile, and, in two, a fatal outcome. Different histologic appearances in lesions from separate sites of the same patient were seen in the cases with epithelioid granulomas and in those with total effacement. The diverse histopathology in lymph nodes involved by LCH is considered in the context of current knowledge of this enigmatic disease.

Giant cell arteritis of the uterus: case report and review

We here report a rare case of giant cell arteritis (GCA) of the myometrium found incidentally in a 68-year-old Caucasian woman presenting with uterovaginal prolapse and a known past history of temporal arteritis/polymyalgia rheumatica. Histology revealed a segmental arteritis of small, medium and some quite large myometrial arteries with extensive destruction of both internal and external elastic laminae. Multinucleate giant cells, lymphocytes and histiocytes were most prominent in the inflammatory infiltrate. The findings in this case are compared with previous reports. In a review of the literature it was found that almost one third of cases presented with generalised symptoms such as fever, anemia, fatigue and weight loss. The symptoms were not immediately recognised as temporal arteritis or polymyalgia rheumatica. On routine physical examination or radiological investigation, benign gynecological pathology such as a simple ovarian cyst or uterine leiomyoma were found. The subsequent unexpected discovery of GCA on histological examination was the critical event in alerting clinicians to the diagnosis of temporal arteritis/polymyalgia rheumatica. Without exception steroid therapy was successful in achieving relief of generalised symptoms.

Familial Hyperphosphatemic Tumoral Calcinosis A Report From Saudi Arabia

The clinical details and radiologic and histopathologic findings of lesions from three male siblings and their female cousin with hyperphosphatemic tumoral calcinosis are presented. The three siblings were children of consanguineous parents. The patients were aged 5, 17, 19, and 20 years; however, they first presented when they were 3.5, 8, 4, and 5 years of age, respectively; resulting in a disease duration ranging from 1.5 to 15 years. All are alive with persistent disease. The eldest patient has an alpha-thalassemia trait. Sites of lesions included the periarticular soft tissues of gluteal region, the shoulder, elbow, interscapular area, axilla, and popliteal fossa. A calcified soft tissue mass was seen radiologically at all sites affected. Histologically, locules of calcified debris surrounded by multinucleated osteoclast-type giant cells and foamy histiocytes characterized all lesions. The cells showed cytoplasmic vacuoles that stained positively both with anti-alpha-1-antichymotrypsin and anti-alpha-1-antitrypsin. Ultrastructurally hydroxyapatite deposits were demonstrable in these cytoplasmic vacuoles. All patients had normocalcemia and hyperphosphatemia. A low normal blood level of 25-hydroxycholecalciferol was noted in the youngest patient. Surgical excision was unsuccessful as the lesions recurred and progressed. Medical therapy may only slow the progression of the disease process.

Solitary and generalized variants of spindle cell xanthogranuloma (progressive nodular histiocytosis)

Twelve cases of solitary spindle cell xanthogranuloma, seven of which had originally been misdiagnosed as dermatofibroma/benign fibrous histiocytoma, were clinicopathologically compared with four cases of progressive nodular histiocytosis, a rare generalized non-X histiocytic disorder. Clinically, a single brown-yellowish papule or nodule is characteristic of solitary spindle cell xanthogranuloma, multiple generalized lesions of progressive nodular histiocytosis. Solitary spindle cell xanthogranuloma occurs with decreasing frequency on the head, neck, upper trunk, or occasionally the extremities of young adults (aged 20-40 years), progressive nodular histiocytosis mostly on the trunk of older patients (aged 40-60 years), both without sex predilection. Histologically, both entities are characterized by predominance (> 90%) of spindle-shaped histiocytes arranged in a storiform pattern. Other mononuclear (vacuolated, xanthomatized, scalloped, oncocytic) and multinucleate (Touton) histiocytes are also regularly seen. Immunohistochemically, both entities exhibit a macrophage/dendritic cell lineage positive for KP1/Ki-M1p (CD68), HAM 56 and factor XIIIa as well as for smooth muscle specific actin and HHF35. Ultrastructurally, dense, regularly laminated, myeloid or pleomorphic cytoplasmic inclusions may be found, but no Birbeck granules are present. This study documents that both solitary spindle cell xanthogranuloma and progressive nodular histiocytosis are distinct entities within the spectrum of a xanthogranulomatous reaction characterized by predominance of spindle-shaped histiocytes.

Tumefactions as an Extravascular Manifestation of Wegenerʼs Granulomatosis

Wegener's granulomatosis appeared as localized or infiltrative tumefactions in six patients. The tissue swellings affected the retroperitoneum, mediastinum (two), breast, retroorbital tissue (two), and gingiva. There was extensive fibroblastic proliferation in each case with a predominantly granulocytic inflammatory component, microabscess formation, and collagen necrobiosis. In one of the mediastinal lesions and in the gingiva, there was a granulomatous component as well. In the breast were scattered multinucleated histiocytes. Necrotizing vasculitis was absent or limited in all cases. All patients responded dramatically to cyclophosphamide and/or prednisone after the diagnosis was established. These observations indicate a role for tissue destruction in Wegener's granulomatosis mediated by granulocytes without a vasculitic component.

A cholesterol granuloma in the maxillary sinus: Report of case

Cholesterol granuloma almost always forms as a result of hemorrhage in a confined space. Presumably the lymphatic drainage is insufficient to completely remove the lipid components of the red cells that remain, and they become crystals of cholesterol and its esters. The immunologic surveillance system regards these crystals as foreign bodies, and reacts by the production of multinucleated giant cells and histiocytes. In histologic preparations, the intermixed cleft-like spaces represent cholesterol crystals that have dissolved due to the alcohol used in the staining procedures. Cholesterol granulomas are frequently found in the middle ear, thyroid adenoma, and other sites. The following is a report of a cholesterol granuloma of the maxillary sinus.