Unusual Histopathological Features Research Articles

Hydatid cyst of axilla masquerading as scrofuloderma

Hydatid disease is an ancient endemic parasitic infestation caused by Echinococcus granulosus, which results in the formation of hydatid cysts in various parts of the body, the liver, and lungs being the most common sites. However, in 15% to 20% of the cases it may occur in unusual sites. We report a 25-year-old male patient who presented with clinical features similar to scrofuloderma in the axillary region but confirmed from histological examination to have hydatid cyst. This case highlights the uncommon site of hydatid cyst and unusual clinical and histopathological features along with the fact that it should be kept in differential diagnosis of nodules and sinuses in the axillary region. The treatment of choice is excision along with combination of albendazole and praziquantel.

Paraganglioma of the cauda equina: a report of two cases with unusual histopathological features

Paragangliomas of the cauda equina are very rare. Preoperatively, they are usually diagnosed as schwannoma. We report 2 cases that exhibited unusual histopathologic structure as well as a typical Zellballen pattern with a highly vascular stroma. The unusual features included papillary, ribboning, and pseudorosette patterns, ganglion cell nests, and melanin pigment. Pathological diagnosis of paraganglioma may be especially difficult when such unusual histopathological features are seen. Correct histopathological diagnosis is important as paraganglioma has a better prognosis than other tumors included in the differential diagnosis for this location.

Clinical, histopathological and mineralogical analysis findings of an unusual case of pneumoconiosis

A 43-year-old man with a long history of dyspnea which had progressively worsened over the preceding month is presented. He had worked in an antimony mine for 3 years. Radiologically, there were diffuse reticulonodular shadowing opacities in both lung parenchymas. Histopathologic examination of the open-lung biopsy specimen revealed alveolar spaces filled with dust-laden macrophages and amorphous proteinaceous semifluid, the latter being immunoreactive for Human Surfactant Apoprotein A, associated with marked interstitial accumulation of the similar-looking macrophages along the bronchovascular bundles and mild interstitial fibrosis. Silicotic nodules or mixed dust fibrosis were not seen. The patient was diagnosed as silicoproteinosis with unusual histopathological features because he had worked in an antimony mine for only 3 years and had 86% silica in a mineralogical analysis. Pneumoconiosis is a rare lung disease which may be confused with other interstitial lung diseases. Clinical, radiological and unusual histopathologic features of this rare case are presented and discussed with the differential diagnosis, especially of mixed dust pneumoconiosis.

Cutaneous Mixed Tumor, Eccrine Variant: A Clinicopathologic and Immunohistochemical Study of 50 Cases, With Emphasis on Unusual Histopathologic Features

Mixed tumor, eccrine type, is a rare cutaneous adnexal neoplasm, mostly reported as isolated case reports. A systematic analysis of its histopathologic and immunohistochemical features has not previously been performed on a large series. The purpose of our investigation was to study a large number of cutaneous eccrine mixed tumors so as to fully characterize the entire spectrum of changes in the epithelial and stromal components, with an emphasis on unusual histopathologic features that may represent a diagnostic pitfall. This article reports a light microscopic and immunohistochemical study of 50 cases of eccrine mixed tumor, complemented by a literature review. Our study identified some unusual histopathologic features, thus extending the morphologic spectrum of this neoplasm. These included prominent cribriform areas, clear cell change, pseudorosette structures, prominent osseous metaplasia, and physaliphorous-like cells. Most of these features have not been previously recorded in eccrine mixed tumors and may represent a potential diagnostic pitfall.

Pure Red Cell Aplasia Associated with Plasma Cell Myeloma: Does Monoclonal Protein Inhibit Erythropoiesis?

AbstractAbstract 642Pure red cell aplasia (PRCA) is a rare hematologic disorder characterized by selective inhibition of red cell precursors in the bone marrow. The pathogenesis of PRCA is unclear. Reported secondary causes of PRCA include thymoma, lymphoproliferative disorders (large granular lymphocyte leukemia, chronic lymphocytic leukemia), and viral infection such as human B19 parvovirus; however, in a large portion of patients the cause of PRCA is not able to be elucidated. In this study, we report a series of PRCA patients with unusual histopathological features and associated increase in clonal plasma cells that appear to represent a previously unrecognized PRCA variant associated with MGUS/plasma cell myeloma.We performed a retrospective analysis of bone marrow biopsies and aspirates from 50 patients diagnosed with idiopathic PRCA at the National Institutes of Health between 2001 and 2009. All samples underwent morphological, immunohistochemical and molecular analysis. Serum protein assays were performed on a cohort of patients that demonstrated increased plasma cells and/or light chain restricted plasma cells.In addition to the classical PRCA finding of marked erythroid hypoplasia with maturation arrest, we found 11/50 (22%) PRCA patients with the following atypical bone marrow features: hypercellularity with increased fibrosis and variable degree of plasmacytosis with light chain restriction and frequent aberrant CD56 or cyclin D1 expression, indicating clonality. Based on CD138 staining, 10 of the 11 (91%) patients had 10–20% plasma cells on marrow biopsies, while 1 patient demonstrated 5% plasma cells. Light chain restriction of plasma cells was morphologically demonstrated in 7/11 (64%) patients. 8/11 (72%) patients demonstrated M-proteins on serum protein electrophoresis (SPEP) and/or immunofixation; 6 of the 7 evaluable patients with M-proteins had a skewed serum free light chain (FLC) kappa/lambda (K/L) ratio. There were 7 IgG M-proteins, and the isotype of the M-protein was not defined for one patient. Mean M-protein concentration was 1.18 g/dL (0.6-2.5 gm/dL). Among the 3/11 (27%) patients without M-protein, 2 patients had a skewed FLC K/L-ratio (normal range 0.26–1.65), and 1 patient had a K/L ratio of 1.57. Based on these findings, 9/11 (82%) patients were diagnosed with plasma cell myeloma, 1 patient with MGUS, and clonality of plasma cells could not be demonstrated in 1 patient. In order to better understand underlying mechanisms, we performed an erythroid colony forming assay by co-culturing normal donor hematopoietic stem cells (HSCs) with serum from a PRCA patient containing M-protein versus serum from a normal donor. Compared to normal serum, colony cultures containing M-protein had a 43% reduction in CFU-E and BFU-E suggesting inhibition of erythroid colonies by the monoclonal protein. Clinically, response rates to daclizumab are increased in idiopathic PRCA compared to PRCA variant associated with MGUS/plasma cell myeloma, 10/23 (43%) vs. 0/6 (0%), respectively, (p=0.04). Among 3/11 patients receiving anti-myeloma therapy, 1 patient had resolution of PRCA and later became transfusion independent after bortezomib and 2 patients were lost to follow-up.Over 20% of patients originally diagnosed with idiopathic PRCA were shown to harbor clonal plasma cells and exhibit atypical histopathological marrow features. CFU-E and BFU-E colony growth from normal donor HSCs was inhibited by patient serum containin M-protein. Resolution of PRCA with transfusion independence was achieved in a patient treated with bortezomib based therapy. These findings point to a novel, previously not recognized pathogenetic mechanism of PRCA associated with relatively low plasma cell burden and demonstrate that these patients may benefit from myeloma based treatment strategies rather than standard immunosuppression. Disclosures:No relevant conflicts of interest to declare.

Granulomatous pigmented purpuric dermatoses: report of three cases and review of the literature

Purpuric pigmented dermatoses represent a form of chronic, recurrent capillaritis characterized by petechiae and purpuric macules over the lower limbs. We report three female cases who presented with clinical features of purpuric pigmented dermatosis with unusual histopathologic features. The first patient had golden-brown pigmented purpura over bilateral knees, shins and dorsal feet. The second patient showed purpuric papules on the medial aspects of the ankles. The third patient presented with numerous petechiae on her lower legs. All three patients demonstrated granulomatous inflammation in addition to the histologic features of pigmented purpuric dermatosis. A total of 11 patients have currently been reported in the literature. A review of the clinical details of the cases revealed a high incidence of hyperlipidemia (7/11) and hypertension (4/11) among these patients.

Treatment of mandibular glandular odontogenic cyst with immediate reconstruction: case report and 5-year follow-up

Glandular odontogenic cysts of the jaw are rare with unusual histopathological features, well-defined limits, and a high recurrence rate when treated conservatively. We describe a 37-year-old white man with such a cyst of the right mandible that was resected, and at follow-up 5 years later there were no signs of recurrence.

Cutaneous epithelioid angiosarcoma: a neoplasm with potential pitfalls in diagnosis

Angiosarcoma (AS) is a rare neoplasm. Cutaneous AS is the most common form of AS. The epithelioid variant of the disease, however, is a rare entity. This subset can histologically mimic non-vascular neoplasms and impose serious challenges in reaching the correct diagnosis. We present five patients with cutaneous epithelioid angiosarcoma (EAS); in none, the clinical diagnosis included a vascular lesion. Three patients had history of breast conservation surgery with/without radiation therapy. Other patients had no previous radiation, and there was no lymphedema in any of the cases. The histopathological examination of the biopsy specimens by hematoxylin and eosin method was not suggestive of a malignant vascular neoplasm initially and the differential diagnoses included carcinoma, malignant melanoma and atypical lymphoid infiltrate. Only after performing immunohistochemical studies that included vascular markers, a definitive diagnosis was possible. Some cases showed unusual histopathological features. Cutaneous EAS is a rare variant of cutaneous AS that can mimic a variety of more common, non-vascular neoplasms, creating a major pitfall in the diagnosis. A careful and thorough histopathological examination and a high index of suspicion, along with appropriate immunohistochemical evaluation, can help reach a correct diagnosis and provide optimal patient care.

Ewing??s Sarcoma With Epithelial Differentiation: A Case Illustrating the Use of Ancillary Testing in Soft-Tissue Tumors With Unusual Histopathologic Features

We have illustrated an unusual example of Ewing sarcoma with genetic confirmation using both fluorescence in situ hybridization and RT-PCR. The use of ancillary testing in this example was not only paramount in arriving at the correct diagnosis but was essential in delivering the preferred therapies and avoiding unnecessary surgery and radiation in this patient. Caution must be taken in interpretation of the results of ancillary testing and it is vital that a good working diagnosis be established before ordering of these tests. Ancillary testing cannot replace a good histologic/immunohistochemical assessment of a tumor, but it can complement a morphologic impression, particularly in difficult cases with unusual features.

Multiple skin metastases of malignant melanoma with unusual clinical and histopathologic features in an immunosuppressed patient

Immunosuppressive regimens may have significant impact on the number of pigmented lesions and the clinical appearance of nevi. Whether immunosuppression can also influence the clinical and histopathologic appearance of malignant melanocytic lesions is still a matter of debate. A patient was immunosuppressed because of heart and bone marrow transplantation. A clinically inconspicuous mole was removed from the left flank and was considered to be a papillomatous nevus. After 1 year, the patient developed multiple pigmented lesions over the entire body, which presented clinically as benign papillomatous nevi and histologically as atypical Spitz nevi. Three months later melanoma metastases were removed from the patient's left axilla, which finally resulted in the death of the patient. Thus, in retrospect, the eruptive pigmented lesions have to be considered as cutaneous melanoma metastases. The atypical clinical and histopathologic appearance of the melanocytic lesions as well as the course of disease may have been influenced by the immunosuppression.

An Unusual Apocrine Carcinoma on the Forehead

We herein report an unusual case of apocrine carcinoma on the forehead. The lesion was formed by the anastomosis of numerous tubular structures with widespread decapitation secretion, thus demonstrating apocrine differentiation. However, we observed some unusual histopathologic features that differed from those found in typical examples of apocrine ductal carcinoma, namely: 1) a relatively well-circumscribed lesion in the dermis, and 2) nodular or solid aggregations composed of basaloid cells. We believe the present case is an apocrine ductal carcinoma, although it has a nodular appearance and basaloid cells. Otherwise, it could be a hitherto undescribed variant of apocrine carcinoma. This apocrine carcinoma on the forehead may have originated from either pluripotential cells or from apocrine glands at an unusual site.

Malignant predominantly minigemistocytic glioma in two infants: a distinctive glioma variant?

We report unusual distinctive histopathological features in malignant supratentorial tumours of two infants (patient 1: congenital, patient 2: 30 months). Both patients had paraventricularly located well-delineated tumours. Gross total resection could be performed and postoperative chemotherapy was administered. At the last follow-up, 18 (patient 1) and 10 months (patient 2) postoperatively, both patients were in continuous complete remission. Histologically, both tumours were characterized by high cellular density and monomorphic appearance. Tumour cells were small to medium-sized and the majority of cells showed a distinctive minigemistocytic shape. A small fraction of cells lacked a distinct cytoplasm. Mitotic figures were abundant, tumour necrosis and hypertrophic vascular proliferations were absent. Immunohistochemically, the tumour cells expressed glial (GFAP, S100) and focally neuronal (NFP) proteins. Comparative genomic hybridization showed few, dissimilar chromosomal aberrations in the two tumours. Although sharp demarcation and monomorphic architecture of both tumours are reminiscent of a primitive neuroectodermal tumour, cytological and immunohistochemical glial differentiation refer to a glial tumour origin. To our knowledge the histopathological features of the described tumours do not correspond unequivocally to any established glioma variant and could represent a distinctive new glioma subtype.

Intraoral proliferative myositis: Case report and literature review

Proliferative myositis is a rare, benign, reactive intramuscular lesion of fibroblastic/myofibroblastic origin; an identical lesion in a subcutaneous or fascial location is referred to as proliferative fasciitis. The rapid growth rate and unusual histopathologic features have frequently been mistaken for a malignant process and have promoted unnecessary invasive procedures. Here we present only the third oral case of proliferative myositis, arising from the tongue of a 65-year-old man. Histologically, the resected lesion was composed of numerous fibroblastic or myofibroblastic spindle cells and variable numbers of large ganglion-like cells infiltrating between and around muscle fascicles, resembling a "checkerboard" configuration. A demographic profile of proliferative myositis of the head and neck is also provided, compiled from 19 patients culled from an English-language literature review and this report. Incisional biopsy or fine-needle aspiration biopsy of proliferative myositis of the head and neck should lead to spontaneous resolution and is, therefore, sufficient to render the diagnosis and to provide conservative treatment. Recurrence is extremely rare.

Base of Skull Chordomas in Children and Adolescents

Chordomas in children and adolescents comprise <5% of all chordomas and most frequently develop in the skull base. These tumors are believed to behave more aggressively than chordomas in adults and may have unusual morphology. This study examines a large series of pediatric skull base chordomas treated with a standardized protocol to characterize the behavior and morphology of these tumors. There were 31 males and 42 females ranging from 1 to 18 (mean 9.7) years. Forty-two cases (58%) were conventional chordomas, some of which had unusual histopathologic features. Chondroid chordomas comprised 23% of cases. Fourteen tumors (19%) were highly cellular and had a solid growth pattern with no myxoid matrix or lobular architecture. Eight of these had cytologic features of conventional chordoma cells including physaliferous cells (cellular chordoma). The remaining cellular tumors were composed of poorly differentiated epithelioid cells set in a fibrous stroma and lacked physaliferous cells (poorly differentiated chordoma). All variants studied by immunohistochemistry showed positive staining for cytokeratin, epithelial membrane antigen, S100 protein, and vimentin. Mitoses and necrosis were seen in all variants. Follow-up data were available for all patients and ranged from 1 to 21 (mean 7.25) years. The survival rate was 81%. All but 1 patient with poorly differentiated chordoma died of disease. Overall, base of skull chordomas in children and adolescents treated with proton beam radiation have better survival than chordomas in adults. However, poorly differentiated chordomas are highly aggressive tumors.

Unusual histopathological features of cutaneous leishmaniasis identified by polymerase chain reaction specific for Leishmania on paraffin-embedded skin biopsies

Cutaneous leishmaniasis (CL) is rare in Northern Europe and may be overlooked because colleagues have little experience with it. To identify manifestations of CL that may escape diagnosis. Correlation of clinical diagnosis and histopathological findings in 28 biopsy specimens taken from 19 patients with CL confirmed by polymerase chain reaction (PCR) specific for Leishmania. In only one patient was the clinical diagnosis CL; other diagnoses included: malignant epithelial neoplasms (5), follicular cyst (2), atypical mycobacteriosis (1), sarcoidosis (2) and lymphoma (1). Lesions were single (15) or few (4) nodules predominantly situated on the extremities or face (16). Histopathological findings were diagnostic of CL in only 10 cases. In nine cases Leishmania was not identified microscopically; histopathological diagnoses were: granulomatous dermatitis (6), lupoid rosacea (1), foreign body granuloma (1) and granuloma annulare (1). Unaltered epidermis (9), nodular infiltrates (5), numerous multinucleated histiocytes (3), palisaded granulomas with fibrinoid centres (2), sarcoidal granulomas (4) and elastophagocytosis (1) misled the histopathologists in these cases. CL seems often to be misdiagnosed clinically in countries where it is not endemic. Histopathologically, CL may be misinterpreted as sarcoidosis, foreign body granuloma, lupoid rosacea and granuloma annulare, especially when Leishmania is not seen microscopically. We suggest that in Northern Europe, PCR for Leishmania-specific DNA should be performed routinely in any granulomatous dermatitis presenting as a single or few nodules on the extremities or face, even when a diagnosis of CL was not considered by the referring clinician.

Reactive Syringofibroadenomatous Hyperplasia in Peristomal Skin with Formation of Hybrid Epidermal-Colonic Mucosa Glandular Structures, Intraepidermal Areas of Sebaceous Differentiation, Induction of Hair Follicles, and Features of Human Papillomavirus Infection

We report a case of reactive syringofibroadenomatous hyperplasia in peristomal skin. The patient was a 62-year-old woman who had undergone abdominoperineal resection of the rectum for rectal adenocarcinoma with subsequent colostomy 2 years earlier. Clinically, a nodule and small, whitish, warty lesions developed at the outer margin of the stoma extending onto the adjacent skin. Following a clinical suspicion of adenocarcinoma, recurrent at the colostomy site, a 5 x 4 x 3-cm excision of the peristomal skin and the affected portion of the stoma was performed and submitted for histologic examination. The biopsy revealed a peculiar composite lesion of reactive syringofibroadenomatous hyperplasia and the excised part of the stoma. Several unusual histopathological features were detected in the syringofibroadenomatous part of the lesion such as the formation of plentiful hybrid epidermal-colonic mucosa glandular structures, intraepidermal areas of sebaceous differentiation, koilocytic changes, induction of rudimentary hair follicles, and intradermal mucinous lakes. The cellular composition of the glandular structures was mainly similar to that seen in a normal colonic mucosa epithelium. They also contained occasional Paneth cells. Being located at a distance from the stoma, these accentuated colonic mucosa epithelial glands reaching the epidermis may be a diagnostic pitfall prompting the consideration of adenocarcinoma involving the stoma. The rudimentary follicles and sebaceous differentiation were probably induced by an altered stroma and/or human papillomavirus (HPV): HPV, type 36 was identified by PCR using consensus primers followed by sequencing of the PCR products.

The Diabetes-Prone NZO/Hl Strain. II. Pancreatic Immunopathology

We report the first combined light and electron microscopic analysis of the pancreas during the development of type 2 diabetes in the New Zealand Obese (NZO) mouse. As in most other polygenic rodent models of type 2 diabetes, hyperglycemia associated with beta cell destruction is male sex-limited. Increasing degrees of hyperinsulinemia and transition to diabetes were clearly reflected by the islet volume fraction, by the beta cell granulation state, and by ultrastructural changes, primarily of the endoplasmic reticulum. One of the unusual histopathologic features of NZO mice of both sexes was the presence of B-lymphocyte enriched leukocytic aggregates in the pancreas. Immunocytochemical analysis of the pancreas of 52-week-old diabetic males indicated enrichment for CD19+ B lymphocytes. Staining of adjacent sections for CD3 and CD5 indicated CD5 coexpression on some of the CD19+ cells, suggesting the presence of the B1-B subset associated with generation of natural autoantibodies in other autoimmune-prone New Zealand mouse strains. In addition, plasma cells in peri-insular leukocytic infiltrates were identified by electron microscopy. Hence, although autoimmunity has previously proven to be a secondary manifestation of beta cell destruction in most rodent models of type 2 diabetes, the present observations suggest that B lymphocyte function, in association with male gender, may contribute to the development of insulin resistance and chronic hyperglycemia in the NZO model.

Lymphadenitis, trans-epidermal elimination and unusual histopathology in human rhinosporidiosis.

From a study of rhinosporidial tissues of 64 human cases of ocular, urethral and nasopharyngeal disease, unusual histopathological features of 27 cases are described. Histopathological evidence of lymphadenitis in rhinosporidiosis is presented for the first time. The phenomenon of 'trans-epidermal elimination' of sporangia of the causative pathogen Rhinosporidium seeberi is illustrated and it is argued that this phenomenon is rather the pathogen's mechanism for endospore-dispersal than a non-specific defence reaction of the host as has previously been suggested. Other unusual appearances described include variations in the intensity and composition of the host-cell infiltrate in tissues from different patients and in different portions of the same tissue, pitfalls in histopathological diagnosis, and unusual appearances of the pathogen. Histopathological clues to the pathogenesis of rhinosporidiosis and mechanisms of anti-rhinosporidial immunity in the host are discussed, illustrating the probable occurrence of immunesuppressive reactions to account for the variations in the density and composition of the host-cell infiltrate and the state of the rhinosporidial sporangia--intact or degenerate--, relating these variations to the chronicity, recurrences and systemic dissemination of rhinosporidiosis.

Subcutaneous trichoblastoma.

We have recently observed three examples of solitary trichoblastomas (TB) with unusual histopathologic features characterized mainly by numerous aggregations of basaloid cells limited to the subcutis. The three trichoblastomas with unusual features were identified from a large series of 38 solitary TB cases collected over a period of 20 years. Clinically, all three neoplasms presented in men (49, 52, and 62 years old) as solitary, 1- to 1.5-cm skin-colored nodules situated on the scalp, face, and lower arm, respectively. Histopathologically, they showed numerous, smooth-bordered aggregations of basaloid cells limited to the subcutis and surrounded by a sclerotic and partly hyalinized stroma. Multiple sections revealed no connections of basaloid aggregations to the overlying epidermis or pre-existing follicular structures. All three cases displayed rather unusual morphologic growth patterns, including areas of variously sized, nodular aggregations of basaloid cells and extensive foci of elongated, thin columns and branching cords of basaloid cells. A striking feature in the stromal component in two cases was the presence of large, prominent areas of hyalinization and sclerosis. Characteristically, all three neoplasms showed numerous foci with rudimentary follicular germs and papillae. Cytomorphologically, the basaloid cells exhibited dark staining nuclei with large prominent nucleoli and scanty, pale or eosinophilic cytoplasm. Variable number of mitotic figures (2-4 mitoses per high-power field) and single necrotic cells were noted. In one case, small, foci of necrosis en masse were observed. Follow-up data after total excision in all three cases (80, 69, and 6 months) revealed no local recurrences. In light of our observations, we suggest that subcutaneous TB represents a rare variant of solitary TB. Besides the exclusive subcutaneous location, this neoplasm also displays a constellation of particular histopathologic features, namely, rather complex epithelial growth patterns and stroma with prominent foci of sclerosis and hyalinization.

Primary Mucinous Carcinoma of the Skin with Unusual Histopathological Features

Primary Mucinous Carcinoma of the Skin with Unusual Histopathological Features