Helpful Diagnostic Feature Research Articles

Eosinophilic inclusions in ependymoma represent microlumina: a light and electron microscopic study.

A study was undertaken to determine the pathological significance of previously unrecognized intracytoplasmic eosinophilic inclusions (IEIs) in ependymoma. The study group consisted of 58 ependymomas, all of which were pathologically characterized and graded according to the 1993 WHO classification. Electron microscopic studies were performed in 16 cases. The study showed that 33 (57%) ependymomas had IEIs and that in 8 cases these were abundant. Round and eosinophilic, their sizes varied from 10 microns to a tiny dot. Similar eosinophilic bodies were also observed between tumor cells. The inclusions were weakly PAS positive. On immunostains, IEIs were frequently positive for glial fibrillary acidic protein, less often for S-100 protein, and for epithelial membrane protein and CAM 5.2. They were negative for AE1/AE3, carcinoembryonic antigen and Ber-EP4. Ultrastructurally, IEIs represented intracytoplasmic lumens containing microvilli and cilia. These microlumina also frequently contained granulo-tubular materials. With reference to tumor subtypes, IEIs occurred most frequently in ordinary and clear cell ependymomas. IEIs were also present in 4 of 6 anaplastic ependymomas studied. In conclusion, IEIs represent microlumina and occur in more than a half of ependymomas including malignant examples. Their finding is a helpful diagnostic feature of ependymoma.

Fine-needle aspiration cytologic diagnosis of giant-cell tumor of the sacrum presenting as a rectal mass: A case report

A giant-cell tumor of the sacrum is rare, and poses significant therapeutic and surgical difficulties largely because of its location. Patients usually present with pain in the lower back radiating to one or both lower limbs, with or without neurological deficit. The index case presented with difficulty in defecation, in addition to pain in both lower limbs for 6 mo. The patient was seen to have a rectal mass, and a per-rectal fine-needle-aspiration was performed. The smears showed a cellular aspirate composed of a large number of osteoclastic giant cells, admixed intimately with clusters and a scattered population of mononuclear cells. Mitotic figures were not observed. Although the differential diagnosis of osteoclastic giant cell-containing lesions is broad, the presence of strong cohesiveness between the mononucleated cells and giant cells in cohesive clusters is a very helpful diagnostic feature, and was a prominent finding in the present case.

METASTATIC OVARIAN NEUROBLASTOMA: A Case Report

Ovarian metastasis of childhood tumors is rare despite their aggressive nature. The childhood tumor that spreads to the ovary most frequently is the neuroblastoma. The clinical features and frequent bilaterality of ovarian metastatic tumors are helpful diagnostic features in many cases, but when the ovarian tumor is the presenting manifestation of the disease, differentiation from various primary ovarian tumors may be difficult. In this paper, a rare case of metastatic ovarian neuroblastoma is reported.

Purpura in infants and children

Hemorrhage into the skin (purpura) may result from abnormalities in any of the three components of hemostasis: platelets, plasma coagulation factors, and blood vessels. The morphology, size, and distribution of the hemorrhagic lesions are helpful diagnostic features. The main causes of purpura in the newborn and the more common hemorrhagic disorders in children are reviewed.Learning objective: At the conclusion of this learning activity participants should have an understanding of the disease processes that cause purpura in the neonate.

Eosinophils in fibrous tracts and near hair bulbs: A helpful diagnostic feature of alopecia areata

Background: When biopsy specimens lack a “swarm of bees” peribulbar lymphoid infiltrate, the diagnosis of alopecia areata depends on the recognition of other histologic features of the disease. Objective: Our objective was to determine the frequency of the presence of eosinophils in biopsy specimens of alopecia areata in relation to the other major histologic features of the disease. Methods: Biopsy specimens from 71 patients with alopecia areata were studied. Results: Eosinophils were present in 38 of the 71 cases. A peribulbar lymphoid infiltrate was absent in 27 of the 71 cases. Eosinophils were present in 13 of these cases. Multiple catagen hairs and pigment casts (features which may lead to confusion with trichotillomania) were present in 39 cases. The presence of eosinophils was found to be a helpful diagnostic feature in cases with potential for misdiagnosis as trichotillomania. Conclusion: Eosinophils are common in all stages of alopecia areata, both within the peribulbar infiltrate and within fibrous tracts. A “swarm of bees” peribulbar infiltrate may be absent. The presence of eosinophils is a helpful diagnostic feature of alopecia areata. (J Am Acad Dermatol 1997; 37:101–6.)

Polymorphous low-grade adenocarcinoma: Glial fibrillary acidic protein staining in the differential diagnosis with cellular mixed tumors

Polymorphous low-grade adenocarcinoma is a recently recognized salivary gland carcinoma arising primarily within the oral cavity. Most of these tumors are readily diagnosed; occasionally, however, they may be confused histologically with cellular mixed tumors. The difficulty stems from the bland cytologic nature of cellular mixed tumors and their organizational diversity, together with the irregular pushing growth at their interface with adjacent soft tissues, on histologic examination. Because of this diagnostic problem, we evaluated the use of glial fibrillary acidic protein localization in the differential diagnosis of polymorphous low-grade adenocarcinoma and cellular mixed tumor. Twelve oral polymorphous low-grade adenocarcinomas (polymorphous low-grade adenocarcinoma) and twelve cellular mixed tumors were selected and stained for glial fibrillary acidic protein (glial fibrillary acidic protein) using a strept-avidin-biotin system and examined independently by each investigator. In addition, five tumors with limited material (three cellular mixed tumors and two polymorphous low-grade adenocarcinoma) from the consultation service of one author were evaluated using the same techniques. Two polymorphous low-grade adenocarcinoma stained positive in very focal areas and only in the epithelial component; staining did not occur in the stroma. Fourteen of fifteen mixed tumors focally to diffusely expressed glial fibrillary acidic protein. Only one tumor did not express glial fibrillary acidic protein. In mixed tumors with only focal staining, the most helpful differential diagnostic feature was positive staining of the mesenchyme-like cells adjacent to epithelial nests. We did not find this latter staining pattern in any of the polymorphous low-grade adenocarcinoma.

Metastatic Ovarian Tumors in Children

Fourteen cases of neoplasms metastatic to the ovaries in children 10 weeks to 15 years of age are reported. Eight tumors were neuroblastomas, 7 primary in the adrenal gland, and 1 primary in the posterior mediastinum. Three tumors were rhabdomyosarcomas primary in the ethmoid sinus, right occipital region, and left thigh, respectively. The final three tumors were a Ewing's sarcoma, a rhabdoid tumor, and a carcinoid tumor primary in the fibula, kidney, and lung, respectively. The ovarian involvement was an autopsy finding in nine of the patients. Three of the remaining five patients presented clinically with manifestations suggesting a primary ovarian tumor, and the final two patients, who had known extraovarian primary tumors, had symptomatic ovarian masses discovered during life. In one case of neuroblastoma and the case of rhabdoid tumor, the ovarian metastases were initially misinterpreted pathologically as primary ovarian cancers; the primary renal tumor was not discovered until autopsy in the latter case. The ovarian tumors were bilateral in 8 of the 14 cases. Ovarian enlargement was present in 10 cases. Our experience and that in the literature indicates that the childhood tumor that spreads to the ovary most frequently is the neuroblastoma and that rhabdomyosarcoma is the most common sarcoma of childhood that spreads to the ovary. The clinical features and the frequent bilaterality of ovarian metastatic tumors are helpful diagnostic features in many cases, but when the ovarian tumor is the presenting manifestation of the disease, is unilateral, or both, differentiation from various primary ovarian tumors may be difficult.

Eosinophilic enteritis presenting as surgical a report of six cases

Eosinophilic enteritis is now commonly diagnosed in northern Queensland, and cases have been seen elsewhere. The patients present with acute abdominal symptoms, which may mimic appendicitis, and many cases are managed by surgery. To facilitate the diagnosis of this unusual syndrome, six surgically treated cases are reported here. Blood eosinophilia may be a helpful diagnostic feature, but in some cases it does not develop until after the acute abdominal episode. Most cases resolve satisfactorily with conservative management.

Differentiation Between Lymphomas and Pseudolymphomas of the Skin by Computerized DNA-Image Cytometry

The histologic and immunohistologic differential diagnosis between pseudolymphomas (PL) and malignant lymphomas (ML) of the skin can be difficult. Since DNA cytometry has been found to be of both diagnostic and prognostic value in various neoplasms, its ability to discriminate between ML and PL in Feulgen-stained imprints of 17 PL and 49 ML skin biopsies was examined by high-resolution image analysis. The reliability of the following algorithms of DNA distribution was evaluated: 1) 2cDI (2c-deviation index), which reflects the variation of the nuclear DNA values around the diploid DNA peak; 2) percentage of cells having a DNA value greater than or equal to 5c (5cER; 5c-exceeding rate); 3) percentage of cells presenting with a DNA value greater than or equal to 4c (4cER). A 2cDI of 0.1 was found to be the most reliable marker for the differentiation between PL and ML. On the basis of this feature, 16 of 17 cases of PL and 46 of 49 cases of ML were correctly classified. The sensitivity, specificity, and efficiency of this feature were 94%. A 5cER greater than or equal to 1% had a specificity of 100%, but the sensitivity was only 43%. For the 4cER, a sensitivity of 61% and a specificity of 94% were found. In conclusion, the calculation of the 2cDI and the 5cER based on high-resolution image analysis provided additional helpful diagnostic features, and therefore should be included as a diagnostic tool. If the 5cER is at least 1%, the diagnosis of a ML can be confirmed with a specificity of 100%.

ENZYME HISTOCHEMICAL INVESTIGATIONS ON BONE AND SOFT TISSUE TUMOURS

Histochemical staining for three hydrolytic enzymes were performed in 35 bone tumours and 43 soft tissue tumours, malignant as well as benign. Osteosarcoma, intra-osseous as well as extra-osseous, revealed characteristic rich staining for alkaline phosphatase, no matter how dedifferentiated the tumour was. Haemangioendothelioma (and normal endothelium), too, showed strong reaction for alkaline phosphatase whereas haemangiopericytoma did not. Alkaline phosphatase furthermore was found in slight to moderate amounts in fibrous proliferations. All other tumours examined were negative. Acid phosphatase was found in almost every tumour investigated except Ewing sarcoma and chondromyxoid fibroma. However, high activity was characteristic of giant cell tumours and malignant fibrous histiocytoma. The inhibition of acid phosphatase by tartrate was complete except in osteosarcoma and giant cell tumours, where only a partial inhibition was seen. There were non-specific esterase reactions in a variety of tumours, but very strong reactions were characteristic of malignant fibrous histiocytoma and giant cell tumours. The reaction could be completely inhibited by the addition of fluoride. In an era of increasing application of immunohistologic techniques in surgical pathology it might be of value to remember that simple enzyme histochemical stainings may provide helpful diagnostic features in the classification of bone and soft tissue tumours.

Abnormalities in granule formation in acute myelogenous leukemia

Granule formation was investigated in differentiating neutrophils of a patient with acute myelogenous leukemia (AML) by means of the combined techniques of electron microscopy and peroxidase cytochemistry. Two important pathologic features were observed: first, an abnormal concentration and packaging of peroxidase into Auer rods in leukemic promyelocytes, and second, the presence of Auer rods surrounded by single-unit membranes in some mature polymorphonuclear leukocytes (PMN). An additional unexpected finding was the discovery of two distinct populations of PMN circulating concurrently; a minor (less than 5%) normal one that contained both peroxidase-positive azurophilic and peroxidase-negative specific granules and a major abnormal one characterized by the absence of specific granules. None of these abnormalities was observed during the two remissions of this patient's disease. During relapse a “hiatus leukemicus” occurred, which also revealed two populations of cells, a majority population of leukemic blasts, and a minority population of a few normal PMN. These findings documented several developmental abnormalities in the differentiating cells of myelogenous leukemia and also suggested that concurrent normal and abnormal populations of PMN may be a helpful diagnostic feature of a leukemic process.

Abnormalities in Granule Formation in Acute Myelogenous Leukemia

Granule formation was investigated in differentiating neutrophils of a patient with acute myelogenous leukemia (AML) by means of the combined techniques of electron microscopy and peroxidase cytochemistry. Two important pathologic features were observed: first, an abnormal concentration and packaging of peroxidase into Auer rods in leukemic promyelocytes, and second, the presence of Auer rods surrounded by single-unit membranes in some mature polymorphonuclear leukocytes (PMN). An additional unexpected finding was the discovery of two distinct populations of PMN circulating concurrently; a minor (less than 5%) normal one that contained both peroxidase-positive azurophilic and peroxidase-negative specific granules and a major abnormal one characterized by the absence of specific granules. None of these abnormalities was observed during the two remissions of this patient's disease. During relapse a "hiatus leukemicus" occurred, which also revealed two populations of cells, a majority population of leukemic blasts, and a minority population of a few normal PMN. These findings documented several developmental abnormalities in the differentiating cells of myelogenous leukemia and also suggested that concurrent normal and abnormal populations of PMN may be a helpful diagnostic feature of a leukemic process.

Leukemic reticuloendotheliosis.

Clinical and hematologic features and survival effects of various types of therapy are presented in 18 cases of leukemic reticuloendotheliosis. Fibroblastic lymphoreticular infiltration of the bone marrow was a helpful diagnostic feature in half the cases and is emphasized.

CONDUCTION VELOCITY OF MOTOR NERVES IN INFANTS AND CHILDREN

The literature concerning the measurement of conduction velocity in human motor nerves and its clinical applications is reviewed. The chief value of the test to the clinician lies in the demonstration of a peripheral neuropathy and in its differentiation from myelopathy and myopathy. It is pointed out that this investigation is often particularly useful in infants and children as it is an objective and relatively painless test requiring little co-operation from the patient. Starting from approximately half the normal adult value at birth in full-term infants the motor nerve conduction velocity normally increases to the full adult level during the first 3 to 5 years of life. In premature infants it begins at a still lower level. This increase is of clinical interest and can be studied serially. There is also a particular developmental aspect in infants in relation to possible delays or disturbances of innervation or myelination. The results of measurements of conduction velocity, chiefly in the median nerves, are reported in 45 "normal" infants and children and in 100 others who had a variety of neurological disorders. The rate was normal in all but one of 33 children with miscellaneous cerebral disorders, including nonspecific mental retardation, Down's syndrome (mongolism), D1 trisomy, hydrocephalus, and organic convulsive disorders. There was a distinct reduction in metachromatic leucodystrophy (2 cases), infantile amaurotic idiocy (1 case), and recurrent and chronic polyneuropathy (3 cases). In 4 children with acute neuronitis there were no demonstrable gross changes in conduction velocity during the first 2 months, while the diminished voltage and increased temporal dispersion of the action potential were more helpful early diagnostic features. Normal results were obtained in benign congenital hypotonia (10 cases), phenylketonuria (3 cases), and ataxia-telangiectasia (1 case). Five children with Friedreich's ataxia were examined and 2 of these had marked clinical fluctuations in the extent of their weakness suggestive of peripheral neuropathy. One of the latter was seen during an acute exacerbation of his weakness when he had a distinctly reduced nerve conduction velocity, and prolonged terminal latency from wrist to thenar eminence. The other was tested during a phase of relative well-being and had a normal conduction velocity but even more prolonged terminal latency than the first. The remaining children had a slowly progressive illness; all of them had normal conduction velocity, but one had just significantly prolonged terminal conduction time. Somewhat slow conduction rates for the age appeared to be present in 1 of 6 infants with arthrogryposis multiplex congenita and in 4 of 14 with clubfoot below the age of 2 years, but the statistical significance of these deviations cannot yet be indicated. The results are discussed, with particular emphasis on developmental aspects and the involvement of the peripheral nervous system in "dysmyelination" and demyelination.