Classic Histologic Findings Research Articles

Pseudomelanosis Duodeni: A Unique Finding from an Upper Gastrointestinal Endoscopy

Purpose: Pseudomelanosis duodeni is a rare, benign condition characterized by dark spots in the duodenal mucosa considered to be a collection of pigment- laden macrophages in the tip of the duodenal villi. There are very few case reports to date describing this condition. In this case report we describe classical endoscopic and histological findings of this rare condition and review the existing literature. Case Report: An 80-year-old black woman with history of mitral valve disease, heart failure, chronic kidney disease (not on dialysis), hypertension, hypothyroidism and diabetes mellitus, was referred for a gastrointestinal endoscopy to work up her anemia. She had required multiple transfusions in the past for anemia and was also on oral iron medication. Upper endoscopy revealed multiple AVMs that were successfully cauterized by argon plasma coagulation. Also noted were patchy abnormal dark pigmentation in the stomach mucosa and diffuse dark pigmentation of entire examined small bowel. Biopsies of the duodenum revealed accumulation of abnormal dark pigment within the macrophages of the lamina propria, which was negative for iron stain. A diagnosis of pseudomelanosis duodeni was made based on the endoscopic and histological findings. Discussion: Pseudomelanosis Duodeni is a rare, benign condition of unknown etiology. This condition was first described by Bisordi and Kleinman in 1976, and since then there have been few cases reported to date. To an endoscopist, it typically appears as a flat, discrete, brown or black speckled appearance of the duodenal mucosa. On histology, the duodenal biopsy shows aggregation of black granular pigment in the macrophages within the tips of the mucosa and do not typically stain for iron. Based on review of literature it occurs mostly in adults (92%) and has a more female predominance (12:1). There is a strong association between this condition with other chronic diseases including hypertension, diabetes and chronic kidney disease and all of these were noted in our patient. The pathogenesis of this condition is not known, and the source of pigment and the mechanism by which this pigmentation occurs is yet be delineated. It has been suggested by using electron probe analysis that coupling of iron with sulfur in pseudomelanosis duodeni affects iron transport and results in accumulation of iron sulfide in macrophages. Unlike in the other organs of the body the deposition of iron does not cause fibrosis and the course of the disease appears more benign. The diagnostic and prognostic significance of Pseudomelanosis duodeni has yet to be determined and guidelines for endoscopic surveillance have yet to be determined.

Severe amiodarone induced pulmonary toxicity.

A known complication of Amiodarone therapy is Amiodarone induced Pulmonary Toxicity (APT). Several features of this adverse effect make it difficult to diagnosis and treat. The case of a 63-year-old male with classic radiographic and histologic findings of APT is discussed. Clinical presentation, pathophysiology, diagnostic findings, and treatment strategies are reviewed. The patient was successfully managed with pulse high dose steroid therapy.

Rosai-Dorfman Disease Treated with Methotrexate and Low-Dose Prednisone: Case Report and Review of the Literature

Rosai-Dorfman disease is a rare condition characterized by an accumulation of histiocytes within lymph nodes and tissue. Treatment is indicated when the condition is highly symptomatic and when widespread involvement causes vital organ compression. To review the classic physical and histologic findings in Rosai-Dorfman disease and summarize the literature supporting the use of methotrexate in this condition. We describe a case of Rosai-Dorfman disease that failed to respond to monotherapy with systemic corticosteroids but improved with the addition of methotrexate. Methotrexate alone or in combination with other agents has been described in at least 12 other cases in the literature and lead to a partial or complete resolution of disease in over half of these. The rapid improvement of clinical and physical symptoms with minimal side effects in our case and others reinforces the utility of antimetabolites in patients with Rosai-Dorfman disease who fail to respond to corticosteroids.

Granuloma anular elastolítico gigantocelular: relato de caso

Annular elastolytic giant cell granuloma is a rare granulomatous skin disease characterized histologically by phagocytosis of elastic fibers by multinucleated giant cells and clinically by annular patches with elevated borders and atrophic centers found mainly on sun-exposed skin. The pathogenesis of the disease is controversial. We report the case of a 44-year-old woman with classical clinical and histological findings of the disease whose condition improved when hydroxychloroquine was administered over a four-week period.

Experience with adrenal schwannoma in a Chinese population of six patients

Benign adrenal schwannoma is an extremely uncommon cause of incidentaloma. This article describes our experience with the diagnosis and treatment of adrenal schwannoma in a Chinese population of 6 patients. To our knowledge, this is the largest series of this uncommon adrenal tumor treated in a single center. From May 1999 to May 2009, 6 patients with incidentally discovered adrenal schwannoma were operated on at a tertiary referral hospital in Eastern China. Clinical details, radiographic features, laboratory examinations, pathological findings, and follow-up data of these patients were analyzed. Of the 6 patients, 4 were females (F) and 2 were males (M), with a mean age of 40.5 yr (range: 30-47, M:F=2:1). The 6 patients were managed with open unilateral adrenalectomy; 5 patients had schwannomas on the left side, and 1 on right side. Abnormal urine catecholamine was detected in 1 patient. The mean pathological size of these tumors was 4.3 ± 1.1 cm. The diagnosis of schwannoma was based on classic histological findings, and supported by immunohistochemistry of S-100, vimentin, and ABC positivity. In the follow- up of 47.5 ± 32.3 months, no recurrence and metastasis were observed. Although there may be some clues for radiological diagnosis of adrenal schwannoma, preoperative misdiagnosis is not infrequent. Those tumors may occasionally have endocrine function. Histological examination is the key of diagnosis, and surgical resection is the treatment of choice once malignancy cannot be excluded by preoperative analyses.

Erdheim-Chester Disease Presenting as Bilateral Clinically Malignant Breast Masses

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis of unknown etiology, the commonest sites of involvement being the long bones, skin, orbit, pituitary and retroperitoneum. Breast involvement is rare, with only four reported cases in the English literature. We present a case of a 78-year-old female presenting with bilateral clinically malignant breast masses, with mammographic and ultrasound findings suggestive of locally advanced bilateral breast cancer. Core biopsies from both breasts showed identical features, with a diffuse xanthomatous infiltrate with scattered Touton-type giant cells and a patchy lymphocytic infiltrate. The cells were CD68 positive, and negative for S100, CD1a and a broad panel of cytokeratins. The patient has a background history of cerebrovascular disease with carotid artery stenosis, and subsequently developed rapid restenosis after carotid endarterectomy. With the combined clinical history and classic histological findings in the breast, a diagnosis of Erdheim-Chester disease was made. This is the fifth case report of Erdheim-Chester disease involving the breast, and only the second case with breast lesions as the presenting symptom. Perivascular infiltration is also a rare but recognized presentation of Erdheim-Chester disease. Histiocytic proliferations including ECD can mimic breast carcinoma clinically, radiologically, and histologically, and should be considered in the differential diagnosis of breast mass lesions.

Histologic Resolution of Pulmonary Interstitial Glycogenosis

Pulmonary interstitial glycogenosis (PIG) is an enigmatic lung disorder of unknown etiology that presents with neonatal respiratory distress. Despite its dramatic clinical presentation, the diagnosis of PIG has a favorable prognosis with rare mortality in the absence of comorbid conditions. In this report, we describe changes in successive lung biopsies in a neonate who presented with respiratory failure and pulmonary hypertension. Diagnostic lung biopsy at 10 days of age exhibited classic histologic and ultrastructural findings of PIG with diffuse expansion of the alveolar interstitium by glycogenated mesenchymal cells. Subsequent to the patient's clinical improvement, a repeat biopsy at 49 days of age showed significant resolution of the disorder. Colocalization of vimentin-immunopositive cells with both phospho-histone H3 and cleaved caspase-3 demonstrated prominent attenuation of mesenchymal cell proliferation and apoptosis in the second biopsy. Although the self-limited nature of PIG has been described clinically, it has never been documented histologically. We present this case to illustrate the clinical and pathologic resolution of the disorder and speculate that the lesional mesenchymal cells may have transient proliferative capacity.

The Role of the Coagulation and Fibrinolytic Pathway in Acute Lung Injury

Acute lung injury (ALI) is a common, life-threatening cause of acute respiratory failure, which is ultimately caused by a variety of local and systemic insults. Alterations in the coagulation and fibrinolysis profiles are present in almost all the patients suffering with ALI. The classic histologic findings in ALI patients include alveolar fibrin formation and microthrombi in the pulmonary vasculature. Decreased circulating levels of protein C and increased concentrations of thrombomodulin are present in patients with septic and nonseptic ALI. The circulating and pulmonary concentrations of plasminogen activator inhibitor-1 (PAI-1) are increased in the setting of ALI, and the degree of elevation in the PAI-1 level directly correlates with mortality. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI. This review summarizes the current understanding of coagulation and fibrinolysis in ALI with an emphasis on the pathways that could be potential therapeutic targets, including the tissue factor pathway, the protein C pathway and the modulation of fibrinolysis via plasminogen activator inhibitor-1.

Immunohistochemical Markers in the Diagnosis of Hepatocellular Carcinoma

Abstract:The diagnosis of hepatocellular carcinoma (HCC) is based on classic histologic findings. However, some cases may need additional studies to clarify the origin of the neoplasm or confirm its malignant nature. Immunohistochemistry is useful not only in determining the hepatic origin but also

Lack of classic histology should not prevent diagnosis of necrolytic acral erythema

We describe a patient who was referred for management of psoriasis unresponsive to treatment. Given the predominantly acral distribution of the patient's rash and his known diagnosis of hepatitis C, we considered the diagnosis of necrolytic acral erythema (NAE) and empirically began treatment with oral zinc sulfate. At follow-up 3 weeks later, the patient had exceptional improvement in his cutaneous disease, supporting our diagnosis of NAE. NAE is a recently described entity, and limited information is known regarding its etiology and pathogenesis; however, previous reports have been fairly consistent regarding the clinical and histopathologic presentation. We describe a patient without the classic histologic or clinical findings of previously described cases of NAE. We believe that it is important to keep the diagnosis of NAE in one's differential for a predominantly acrally distributed rash. Furthermore, we recommend additional work-up, including hepatitis C status and zinc levels, as well as possible treatment with oral zinc sulfate in patients with a potential diagnosis of NAE.

An uncommon type of adrenal incidentaloma: a case report of a schwannoma of the adrenal medulla with cytological, histological, and ultrastructural correlation

Benign nerve sheath tumors of the adrenal gland are an extremely uncommon cause of an incidentaloma. We report a case of a schwannoma of the adrenal medulla in an asymptomatic 51-year-old woman, which was discovered incidentally on a computed tomography scan after routine workup for her degenerative joint diseases of the lumbar spine. Because of the large size and unknown biologic nature of the tumor by clinical and radiographic studies alone, an adrenalectomy was performed. The gross specimen featured a well-circumscribed medullary based tumor with cystic degeneration. The diagnosis of a nerve sheath tumor was based on classic histological findings, supported by S-100 positivity, and ultrastructurally by the finding of typical Schwann cells. The cytological diagnosis from the fine-needle aspiration biopsy material obtained at the time of gross examination was much more challenging on retrospective review. The aspirated material showed a round- to oval-cell predominant smear with occasional striking anisonucleosis, intranuclear inclusions (so-called ancient change), and pigment deposition. A review of the histogenesis and differential diagnosis of this common nerve sheath tumor in this unusual location is discussed.

Clinicopathologic study of Churg-Strauss syndrome

To study the clinical and pathologic features of Churg-Strauss syndrome (CCS). Three cases of Churg-Strauss syndrome, including 1 autopsy case and 2 cases with open thoracoscopic lung biopsy, were retrospectively reviewed. All the tissue samples were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. The first patient was a 68-year-old man who had history of asthma for 4 years, with recent exacerbation and chest pain for 2 weeks. Patient died 1 day after admission due to myocarditis and myocardial infarction. He did not have peripheral eosinophilia, skin or paranasal sinus pathology. CSS represented an incidental autopsy finding and he had never been treated with corticosteroid before. The other 2 patients were a 58-year-old male and a 12-year-old female, respectively. Both had history of asthma, peripheral eosinophilia and lung consolidations on computed tomographic examination. Pathologically, all cases showed vasculitis, perivascular allergic-type granulomas, eosinophilic pneumonia and asthmatic bronchitis. Thorough understanding of the clinical and pathologic criteria is essential for arriving at a correct diagnosis of CSS. Although some patients may present with atypical symptoms, lung biopsies often reveal the classic histologic findings which include vasculitis and perivascular allergic granuloma formation.

A novel murine model for the study of human renal cryoablation

to develop a reproducible, non-debilitating in vivo murine model of human renal cryoablation using a standard closed argon-delivery system. Custom engineered 2-mm conical tip cryoprobes for use on the standard argon-based cryoablation unit (Endocare, Inc. Irvine, CA, USA) were used to create small controllable iceballs (−160 °C) in the mouse kidney. The time to create a 4-mm cryolesion was compared using a contact vs puncture technique in 10 mice. To show consistency of the induced-freeze injury, a 4-mm iceball was created in 20 murine renal units and the time to creation and the size of the resultant cryolesion measured. To investigate lesion regression and histological changes, we created a 4-mm renal cryolesion in 28 mice and killed four each at 1, 3, 7, 14, 21, 28, and 35 days. The measured coronal cross-sectional area of the cryoablation site at necroscopy was compared to the initial calculated area as a percentage. To assess renal preservation, blood urea nitrogen (BUN) and creatinine levels at 1 week after cryoablation or sham ablation was compared (10 mononephric mice in each group). The time to create the desired iceball was 1.9 times quicker using the puncture vs the contact technique. The mean (sd) time to forming a 4-mm iceball was 35.3 (4.8) s with a mean maximum length of the resultant post-thaw injury of 5.7 (0.5) mm and a 9% coefficient of variance. Regression analysis of the two-dimensional cross-sectional coronal area of the cryolesion showed a statistically significant linear pattern of regression over time (P = 0.037) and classic histological findings. There was no significant difference in the BUN or creatinine levels in mononephric mice 1 week after cryotherapy compared with the sham-ablated controls. We describe a reproducible, non-debilitating, easily manipulated murine model for the study of human renal cryoablation.

Neurodevelopment of C57B/L6 mouse brain assessed by in vivo diffusion tensor imaging

Heterogeneous spatiotemporal patterns of C57B/L6 murine brain maturation during the first 7 weeks after birth (i.e. P15 to P45) were assessed in vivo by diffusion tensor imaging (DTI) at 9.4 T. Maps of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were used to assess developmental changes. Because directionally encoded color (DEC) maps provide an efficient and straightforward way to visualize anisotropy direction, they were used to highlight the orientation-dominant anisotropic tissues. In the corpus callosum, the increases in FA (approximately 0.4 to approximately 0.6 from P15 to P45) were primarily dominant in the medial-lateral direction, whereas the ADC decreased slightly (approximately 0.8 x 10(-3) to approximately 0.5 x 10(-3) mm(2)/s from P15 to P45). Similar increases in FA (approximately 0.3 to approximately 0.4 from P15 to P45) and decreases in ADC (approximately 0.8 x 10(-3) to approximately 0.5 x 10(-3) mm(2)/s from P15 to P45) were found in the cingulate, but these anisotropic changes were dominant in the anterior-posterior direction. In the caudate putamen, there were significant FA increases (approximately 0.1 to approximately 0.2 from P15 to P45) dominant in the dorsal-ventral and anterior-posterior directions, whereas the ADC increased rapidly early in development (approximately 0.3 x 10(-3) to approximately 0.7 x 10(-3) mm(2)/s from P15 to P17). There were no significant changes in tissue anisotropy in the somatosensory regions (whisker, forelimb), but the ADC decreased slightly (approximately 0.7 x 10(-3) to approximately 0.5 x 10(-3) mm(2)/s from P15 to P45). Although the major differences in DEC values were mainly observed in white matter pathways, other cortical and subcortical regions showed some potential morphological changes that were consistent with classical histological findings. In summary, these results show that high-resolution DTI at high magnetic fields allows detection and quantification of brain structures throughout normal development in C57B/L6 mice in vivo.

Klebsiella rhinoscleromatis of the membranous nasal septum

Rhinoscleroma is a chronic, infectious, granulomatous disease that may present with mass lesions in the respiratory tract anywhere from the nose to the trachea. The nose is involved in 95-100 per cent of cases. There are three stages of the disease: catarrhal-atrophic, granulomatous (also known as hypertrophic) and sclerotic. The diagnosis is made either by positive Klebsiella rhinoscleromatis culture or from the classic histological findings of Mikulicz cells and transformed plasma cells with Russell bodies. Rhinoscleroma is endemic to areas of Africa, South-East Asia, Mexico, Central and South America, and Central and Eastern Europe, and it has been associated with low socioeconomic status. In the past, rhinoscleroma was infrequent in the US population but, with current trends in migration, the incidence of rhinoscleroma may be on the rise. There is often a delay in diagnosis in non-endemic areas such as the US due to unfamiliarity with the disease, the stage-dependent clinical and histological manifestations of disease, and the fact that only 50-60 per cent of cultures are positive for K rhinoscleromatis. Such late diagnosis leads to increased morbidity in the form of nasal and airway obstruction and nasal deformity from erosive processes. Rhinoscleroma is difficult to cure and prone to recur. Currently, the recommended treatment consists of a combination of surgical debridement and long-term antibiotic therapy. We present a case report of a culture-positive diagnosis of rhinoscleroma, and we review the existing literature.

Management of Scalp Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans is a relatively rare, locally aggressive soft tissue tumor. Less than 5% of these tumors are located on the scalp; however, the recurrence rates for this region are high compared with those of more common locations, such as the trunk and proximal extremities. Standards for the management of dermatofibrosarcoma protuberans in general have been established in the literature, including wide local excision and Mohs micrographic surgery. To describe optimum treatment options for primary and recurrent dermatofibrosarcoma protuberans of the scalp based on cases from Roswell Park Cancer Institute (RPCI) and from the literature. Five cases from RPCI and 23 cases from the literature were reviewed. Age, sex, history, tumor size and level of invasion, treatment, reconstruction method, and follow-up were compiled from each case. Twenty-eight cases of scalp dermatofibrosarcoma protuberans were found; 13 were primary, 8 were recurrent, and 3 had persistent positive margins. Fifty-eight percent had classic histologic findings; seven tumors invaded beyond the periosteum. Twenty tumors were treated by surgical excision, whereas eight tumors were treated with Mohs micrographic surgery, requiring between two and four layers. Advanced surgical reconstruction was used in most cases to close the defects. Four patients experienced one tumor recurrence, whereas three other patients had several local recurrences. One patient died of his disease, and one died during surgical treatment of dermatofibrosarcoma protuberans. Mohs micrographic surgery or a modified version may be the best treatment option for scalp dermatofibrosarcoma protuberans to ensure complete removal of tumor and minimize recurrence. Surgeons should be prepared for advanced reconstruction following tumor removal.

Myeloma of the jaw bones: a clinicopathologic study of 33 cases.

A clinicopathologic study of 33 cases of plasma cell neoplasm of the jaw bones was performed. The Mayo Clinic's pathology files through 1995 were reviewed for cases of plasma cell neoplasia involving the jaw bones. Clinical data, radiologic features, and follow-up data were obtained from the hospitals of origin, referring physicians, and Mayo Clinic files. The histopathologic features of the 33 tumors were studied. There were 21 (64%) male and 12 (36%) female patients, ranging in age from 25 to 81 years (mean, 57.7 years). Twenty-one tumors (64%) were classified as solitary plasmacytoma of bone (SPB) and 12 (36%) as multiple myeloma (MM). Among the SPB cases, 15 (71%) involved the maxilla, and 14 patients were men, with a mean age of 57.1 years. Abnormal serum protein was found in 22% of patients, and in nine patients (43%) the SPB converted to MM after a median of 20.7 months. Among the MM cases, seven (58%) affected the maxilla, seven patients were men with mean age of 58.3 years, and abnormal serum protein and Bence-Jones protein were found in 42% and 73% of the patients, respectively. Anaplastic histology was identified in seven (33%) SPB and six (50%) MM tumors, and amyloid was present in eight (38%) SPB and three (25%) MM tumors. Twelve (57%) SPB patients died of the disease after a median disease-free survival of 6.75 years, and the overall and disease-free survival rates at 5 and 10 years were 52%, 33%, 33%, and 24%, respectively. All MM patients died of the disease after a median survival of 17.6 months, and the 5-year and 10-year survival rates were 8% and zero. Eighty-six percent of the SPB patients with anaplastic histologic findings died of the disease (average survival, 3.8 years), whereas only 43% of those with classic histologic findings died of the disease (average survival, 11.75 years). Among MM patients, anaplastic histologic findings were associated with a 9-month average survival (26-month average survival for MM patients with classic histologic findings). SPB patients seem to have a better prognosis than MM patients, and 43% of SPB tumors convert to MM after an average of 20.7 months. Anaplastic histologic findings seem to be associated with lower survival rates and periods for SPB patients and lower survival periods for MM patients.

Aneurysmal bone cyst of the fibula

Aneurysmal bone cysts are benign, expansile lesions that are not at all uncommon in the lower extremity. These lesions are difficult to recognize clinically. This paper is a thorough review of the current literature regarding aneurysmal bone cysts. After this review, one should be able to diagnose and appropriately treat aneurysmal bone cysts. Also provided is a case report with classic histologic, clinical, and radiographic findings that was treated by en bloc resection.

The therapeutic dilemma of inclusion body myositis

Inclusion body1 myositis (IBM) has unique clinical, histologic, and therapeutic features that distinguish it from other inflammatory myopathies, particularly polymyositis and dermatomyositis. [1-3] Although similar but noninflammatory familial forms are recognized, this editorial is concerned with only the sporadic form of the disease. IBM patients develop slowly progressive weakness, usually after the age of 50. The slow evolution of the disease is one of the primary reasons for the delay in diagnosis, which averages approximately 6 years from the onset of symptoms. [1] Men are much more commonly affected than women. The clinical hallmark of IBM is early weakness and atrophy of the quadriceps, wrist and finger flexors, and ankle dorsiflexors. Severe weakness in these muscle groups is so characteristic of IBM, that even if the classic histologic findings are not present on muscle biopsy, a presumptive diagnosis of possible IBM should be considered. [1,2] Classic light microscopy features are endomysial inflammation with invasion of non-necrotic muscle fibers, eosinophilic cytoplasmic inclusions, and rimmed vacuoles within the muscle fibers that contain amyloid deposits. [4] Electron microscopy reveals an accumulation of cytoplasmic and intranuclear 15- to 21-nm tubofilaments. The inflammatory response consists of macrophages and CD8 sup + cytotoxic/suppressor T lymphocytes and is often the most prominent initial histologic finding. [5] The other pathologic features may not be identified on the initial muscle biopsy, often necessitating second or third biopsy for confirmation. Despite the inflammatory response …

Characterization and biological properties of a new staphylococcal exotoxin.

Staphylococcus aureus strain D4508 is a toxic shock syndrome toxin 1-negative clinical isolate from a nonmenstrual case of toxic shock syndrome (TSS). In the present study, we have purified and characterized a new exotoxin from the extracellular products of this strain. This toxin was found to have a molecular mass of 25.14 kD by mass spectrometry and an isoelectric point of 5.65 by isoelectric focusing. We have also cloned and sequenced its corresponding genomic determinant. The DNA sequence encoding the mature protein was found to be 654 base pairs and is predicted to encode a polypeptide of 218 amino acids. The deduced protein contains an NH2-terminal sequence identical to that of the native protein. The calculated molecular weight (25.21 kD) of the recombinant mature protein is also consistent with that of the native molecules. When injected intravenously into rabbits, both the native and recombinant toxins induce an acute TSS-like illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death, with classical histological findings of TSS. Furthermore, the activity of the toxin is specifically enhanced by low quantities of endotoxins. The toxicity can be blocked by rabbit immunoglobulin G antibody specific for the toxin. Western blotting and DNA sequencing data confirm that the protein is a unique staphylococcal exotoxin, yet shares significant sequence homology with known staphylococcal enterotoxins, especially the SEA, SED, and SEE toxins. We conclude therefore that this 25-kD protein belongs to the staphylococcal enterotoxin gene family that is capable of inducing a TSS-like illness in rabbits.