Spectrum Of Histological Appearances Research Articles

A STUDY OF HISTOMORPHOLOGICAL SPECTRUM OF HYPERPIGMENTED SKIN LESIONS IN ADULTS

Background: Hyperpigmentary skin disorders may be dened as increased pigmentation of the skin and/or mucus membranes. Pigmented skin lesions comprise a large component of most histopathologists' workload, and although there is a wide spectrum of histological appearances most can be reported as simple benign naevi. Pathologic examination often serves as a complementary or a conrmative part of the diagnosis. The histologybased treatment principles may be helpful for establishing a standardized treatment algorithm for hyperpigmented skin lesions. A prospective study was conducted to assess histomorphological features of hyperpi Methods: gmented skin lesions. The study included 60 patients for a duration of 2 years. Clinical history like age, sex, site, duration of the lesion, size of the lesion, signicant medical history, and clinical diagnosis were noted. Out of 60 cases, major Result: ity (40 %) were classical lichen planus and its variants. Most of cases were in the age group of 21–30 years and showed male preponderance with both upper and lower limbs as the most common site of distribution. In present study, Conclusion: hyperpigmented skin lesions were most common in males with lichen planus as the most common histopathological diagnosis. The histopathologic examination serves as a complementary or a conrmative part of diagnosis, which helps in management of these patients.

Non-colorectal non-neuroendocrine liver metastasis: a narrative review of surgical treatment.

The liver is the main site of metastatic disease, and cancer metastases remain the main limit to successfully managing the malignant disease. Liver resection (LR) for the treatment of metastatic cancer has been described for over a hundred years and is widely accepted. The role of surgery in managing non-colorectal non-neuroendocrine liver metastasis (NCNNLM), evidence is still lacking due to different factors: the paucity of cases, the wide variety of histological subtypes of the primary disease and its biological behavior, and the absence of prospective studies. We performed a narrative review of peer-reviewed articles related to the surgical outcomes of NCNNLM. The aim of this review is determining the utility of surgery in NCNNLM, with attention to minimal invasive LRs. We analyzed the role of LR for NCNNLM according to the different cancers: digestive and non digestive. NCNNLM encompass a huge spectrum of histologic appearances. LR for limited NCNNLM may offer a curative option, but liver recurrence occurs frequently. Our ability to significantly predict the outcome is poor. The cytotoxic chemotherapy and biologic agents have significantly altered the surgical treatment of LM. The latter treatments can convert inoperable patients into operable ones, with a clear relationship between the degree of resectability in patients judged inoperable at referral and the rate of response to the treatment scheme.

Pearls and Updates in Dermatopathology for the General Surgical Pathologist: Experts Weigh In on What You Need to Know.

Pearls and Updates in Dermatopathology for the General Surgical Pathologist: Experts Weigh In on What You Need to Know.

Nipple leiomyoma: A rare neoplasm with a broad spectrum of histologic appearances

Cutaneous leiomyomas are rare benign smooth-muscle tumors. These lesions are distinguished based on their cell of origin and are subclassified as pilar leiomyoma, angioleiomyoma, and genital-type leiomyoma. Nipple leiomyoma is the least common genital-type leiomyoma, arising from the dartoic muscle cell of the nipple. Histologic examination of the lesion is necessary for definitive diagnosis, and these uncommon tumors can pose a diagnostic challenge. We describe herein a series of six nipple leiomyomas with a spectrum of histologic appearances.

Atypical Spindle Cell Lipomatous Tumor: Clinicopathologic Characterization of 232 Cases Demonstrating a Morphologic Spectrum.

The classification of atypical adipocytic neoplasms with spindle cell features remains challenging. To better define this category of low-grade lipomatous neoplasms, we present herein the clinical, histologic, and immunohistochemical characteristics of a large series of 232 atypical spindle cell lipomatous tumors. The lesions affected 140 males and 92 females, at an average age of 54 years (range, 6 to 87 y), clinically presenting as a persistent or enlarging mass with a median size of 5 cm. The anatomic distribution of the tumors was wide, predominating in the limbs and limb girdles (147 cases, 63%), mainly in the hands and feet (17% and 11%, respectively), with equal distribution between subcutaneous and deeper locations. Microscopic examination revealed a spectrum of histologic appearances. All cases consisted of a poorly marginated proliferation of mildly atypical spindle cells set in a fibrous or myxoid stroma, with a variably prominent admixed adipocytic component showing variation in adipocyte size and scattered nuclear atypia, frequently with univacuolated or multivacuolated lipoblasts. Tumor cellularity and the relative proportion of the different components were very variable. Tumor margins were often ill defined with invasion into surrounding tissues. Two tumors showed morphologic features reminiscent of dedifferentiation. By immunohistochemistry, the neoplastic spindle cells expressed CD34 (64%), S100 protein (40%) and, less frequently, desmin (23%). Expression of Rb was lost in 57% of cases examined. MDM2 and CDK4 were never coexpressed and FISH for MDM2 amplification was consistently negative, highlighting critical biological differences from atypical lipomatous tumor/dedifferentiated liposarcoma. The morphologic differential diagnosis of atypical spindle cell lipomatous tumor is broad, and includes spindle cell lipoma, diffuse neurofibroma, mammary-type myofibroblastoma, dermatofibrosarcoma protuberans, fat-forming solitary fibrous tumor, and morphologically low-grade malignant peripheral nerve sheath tumor. Most patients underwent surgical excision of the primary mass. With a median follow-up of 4 years (range, 1 mo to 20 y), 87% of patients (63/72) were alive with no evidence of recurrence or metastatic disease. Local recurrence of the tumor was observed in 12% of patients (9 out of 72, multiple in 3 of them) at intervals between 6 months and 17 years after resection of the primary tumor. None of the patients developed tumor metastasis or died of disease. Identification of the neoplastic adipocytic component admixed with spindle cells, and recognition of the range of histologic appearances are key for the diagnosis of atypical spindle cell lipomatous tumor. Whereas the risk of metastatic dissemination is minimal, there is a non-negligible risk for local recurrence (13%) which warrants surgical resection with clear margins whenever feasible.

Psoriasiform dermatitides: A brief review.

Psoriasis vulgaris (PV)-the prototypical "psoriasiform" dermatitis-may assume a spectrum of histologic appearances, depending on whether it has been treated or not. Because of that relative lack of morphological uniformity, other skin disorders that feature epidermal acanthosis, with or without associated inflammation, may be confused diagnostically with PV. This brief review considers the clinicopathologic attributes of PV and its imitators, including chronic spongiotic dermatitides, lichen simplex chronicus, prurigo nodularis, pityriasis rubra pilaris, psoriasiform secondary syphilis, and Reiter syndrome.

Sebaceous variant mucoepidermoid carcinoma in a pediatric patient: Diagnostic pitfalls and management

Abstract Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy of childhood. Early diagnosis is essential in determining prognosis and guiding treatment. This can be difficult as it has a spectrum of histological appearances. Here we present the case of a 14-year-old with a high-grade, sebaceous variant. Though initially diagnosed as benign sebaceous adenoma, fine needle aspiration performed for suspected recurrence revealed MEC. After parotidectomy confirmed this finding, a substantial defect remained and reconstruction using an anterolateral thigh free flap was performed. Furthermore, radiation was implemented and thought to have played a role in the successful outcome of this patient.

Metastatic melanoma: Pathologic characterization, current treatment, and complications of therapy.

Metastatic melanoma (MM) has the potential to involve virtually any anatomical site, and it also has a wide spectrum of histological appearances. General clinicopathologic data pertaining to MM are presented in this review, together with a discussion of its differential diagnosis and therapy. "Biological" agents used in the treatment of melanoma are considered, along with the pathological features of the complications that they may cause.

Ovarian low grade serous carcinoma: A case report

<h3>Case report</h3> We present a case of a 76-year-old woman with bilateral ovarian masses and a right upper quadrant cyst detected on imaging. Histology of the solid tumour component in both ovaries showed a low grade serous carcinoma with sheets and irregular nests of cells with uniform round to oval nuclei and evenly distributed chromatin. The solid component merged with a cystic component, showing variable features of serous cystadenoma and borderline serous change. The cells showed positive staining for WT-1, and were negative for p53. The right upper quadrant cyst showed similar features. <h3>Discussion</h3> Low grade and high grade ovarian serous carcinomas are two distinct tumour types with different underlying pathogenesis, molecular events, and prognosis. Low grade serous carcinomas are hypothesised to evolve from adenofibromas or borderline tumours, and have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations. This is termed the Type I pathway. The progression to invasive carcinoma is a slow step-wise process. Low-grade tumours are indolent and have better outcome than high-grade tumours. In contrast, high grade serous carcinomas arise via the Type II pathway and the vast majority are characterised by TP53 mutations and lack mutations in KRAS, BRAF, or ERBB2. Immunohistochemical stains for p53, pl6, p53 and Ki-67 for distinction of low- from high-grade tumours can be helpful in selected instances. This case is presented to show the spectrum of histological appearances in a low grade ovarian serous carcinoma, for instance areas resembling serous cystadenoma through to borderline serous change.

Clinicopathological Analysis of 21 Thymic Neuroendocrine Tumors

BackgroundThymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia.MethodsWe reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features.ResultsIt showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver.ConclusionsIn conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.

Characterization of primary wilms tumor cultures as an in vitro model

Functional analysis of gene candidates and testing of novel therapeutics in Wilms tumors (WT) has been hampered by the lack of in vitro model systems. WT are characterized by a spectrum of histological appearances, but published cell lines are mostly derived from rare anaplastic variants or even non-WT. There has been some success in establishing primary cultures, but these are often poorly characterized or only derived from less frequent WT1 mutant tumors. We report the generation of a set of primary WT-cell cultures using a simple cultivation protocol. Our cultures could be established after preoperative chemotherapy and irrespective of histological subtypes or genetic alterations. The presence of tumor-specific genetic alterations validates these cultures as being tumor-derived. Genetic characterization is of utmost importance as some cultures with similar morphological appearance lacked such alterations and either represent clonal variants or normal cells. By immunohistochemistry, the cells are either epithelial or more mesenchymal, and the latter exhibiting a longer life span with 30 or more passages before undergoing senescence. This may be related to WT being embryonal tumors with a strong differentiation potential that may prevail in vitro. Telomeres progressively shorten with cultivation, but their length does not predict lifespan. hTERT transfection may partly allow establishment of immortalized lines, because 2/7 cultures avoid senescence even in later passages. Importantly, these cells can be efficiently manipulated by transfection, making them a useful model system for in vitro testing.

Selected recent advances in the pathology of salivary neoplasms

This review concentrates on significant developments in salivary pathology since the 2005 WHO classification was written. • Sclerosing polycystic adenosis is a rare lesion often mistaken histologically for carcinoma. Previously thought to be a reactive fibro-inflammatory process, recent evidence of clonality suggests it may be neoplastic. • Histological grading of mucoepidermoid carcinoma has been shown to have clinical relevance, but it is not clear yet which is the best method. Also, other prognostic indices, particularly MIB1 proliferation may be useful in practice. • Epithelial–myoepithelial carcinoma has been known as mainly a clear cell tumour, but it has now been recognized to have a much wider spectrum of histological appearances. • Various morphological variants of salivary duct carcinoma have been described, and a possibly clinically significant molecular classification has been proposed. • The relationship between low-grade cribriform cystadenocarcinoma and salivary duct carcinoma remains unclear.

Gastrointestinal stromal tumors: a review of the literature.

Gastrointestinal stromal tumors are mesenchymal neoplasms with a spectrum of histologic appearances and biologic activity. The morphologic classification of these lesions has evolved over time, and molecular analysis has led to a better understanding of their nature. The histologic differential diagnosis for these lesions is broad and includes many spindle cell lesions of the gastrointestinal tract, including neoplasms of true smooth muscle and neural origin, proliferating fibrous lesions, metastatic neoplasms, and primary sarcomas of vascular and adipose origin. Immunohistochemical studies that include CD117 have become invaluable in the classification of mesenchymal lesions arising in the gastrointestinal tract. Treatment of gastrointestinal stromal tumors has historically been involved surgery, but the use of the chemotherapeutic agent imatinib mesylate for advanced disease has made accurate classification even more important. The molecular features have not only allowed us to understand the pathogenesis of these tumors but also have proven to be associated with response to kinase inhibitors.

Gastrointestinal Stromal Tumors: A Review of the Literature

Gastrointestinal stromal tumors are mesenchymal neoplasms with a spectrum of histologic appearances and biologic activity. The morphologic classification of these lesions has evolved over time, and molecular analysis has led to a better understanding of their nature. The histologic differential diagnosis for these lesions is broad and includes many spindle cell lesions of the gastrointestinal tract, including neoplasms of true smooth muscle and neural origin, proliferating fibrous lesions, metastatic neoplasms, and primary sarcomas of vascular and adipose origin. Immunohistochemical studies that include CD117 have become invaluable in the classification of mesenchymal lesions arising in the gastrointestinal tract. Treatment of gastrointestinal stromal tumors has historically been involved surgery, but the use of the chemotherapeutic agent imatinib mesylate for advanced disease has made accurate classification even more important. The molecular features have not only allowed us to understand the pathogenesis of these tumors but also have proven to be associated with response to kinase inhibitors.

Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN).

In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function. An international working group of nephrologists from 11 Fabry centres identified adult Fabry patients, and pathologists scored histologic changes on renal biopsies. A standardized scoring system was developed with a modified Delphi technique assessing 59 Fabry nephropathy cases. Each case was scored independently of clinical information by at least three pathologists with an average final score reported. We assessed 35 males (mean age 36.4 years) and 24 females (43.9 years) who mostly had clinically mild Fabry nephropathy. The average serum creatinine was 1.3 mg/dl (114.9 micromol/l); estimated glomerular filtration rate was 81.7 ml/min/1.73 m(2) and urine protein to creatinine ratio was 1.08 g/g (122.0 mg/mmol). Males had greater podocyte vacuolization on light microscopy (mean score) and glycosphingolipid inclusions on semi-thin sections than females. Males also had significantly more proximal tubule, peritubular capillary and vascular intimal inclusions. Arteriolar hyalinosis was similar, but females had significantly more arterial hyalinosis. Chronic kidney disease stage correlated with arterial and glomerular sclerosis scores. Significant changes, including segmental and global sclerosis, and interstitial fibrosis were seen even in patients with stage 1-2 chronic kidney disease with minimal proteinuria. The development of a standardized scoring system of both disease-specific lesions, i.e. lipid deposition related, and general lesions of progression, i.e. fibrosis and sclerosis, showed a spectrum of histologic appearances even in early clinical stage of Fabry nephropathy. These findings support the role of kidney biopsy in the baseline evaluation of Fabry nephropathy, even with mild clinical disease. The scoring system will be useful for longitudinal assessment of prognosis and responses to therapy for Fabry nephropathy.

Dermal melanocytoses and variants

Dermal melanocytoses form a spectrum of benign intradermal melanocytic lesions composed of dendritic melanocytes, the most common of which is the blue naevus. A variety of clinical and histological appearances may be assumed, some of which can be worrisome both to the clinician and pathologist, with the most difficult differential diagnosis, in some instances, lying with malignant melanoma. This review presents and discusses the spectrum of histological appearances of this diverse group of lesions, and highlights the clinicopathological variants which are most likely to cause diagnostic difficulty. The lesions that form this spectrum and therefore will be discussed include the dermal melanocytoses such as the Mongolian spot, blue naevus and its variants, deep penetrating naevus, melanoma arising within a blue naevus and, finally, although not a member of this group, cutaneous metastatic melanoma mimicking blue naevus.

Lipomatous mixed tumor with follicular differentiation of the skin

A very rare case of cutaneous mixed tumor with numerous adipose tissue and hair follicular structures in a 67-year-old Japanese male was reported. A well-circumscribed tumor was in the subcutaneous tissue of the cheek and far from the parotid gland. Histologically, the tumor consisted of an admixture of the adipose tissue, fibromyxoid tissue with spindle cells, and branching tubular structures. Outer layers of ductal epithelial cells and single spindle cells were often in a transition, likely as typical mixed tumor. Branching ducts connected with keratinous cysts, strands of trichoblastic basophilic cells and clear cell nests. There was a gradual transition, between small-sized adipocytes and vacuolated spindle cells. No chondroid stroma was seen. To our knowledge, this tumor is the first case of a lipomatous mixed tumor with hair follicular differentiation. The case indicates an additional wide spectrum of histologic appearances of cutaneous mixed tumor.

Persistent nodules at injection sites (aluminium granuloma)—clinicopathological study of 14 cases with a diverse range of histological reaction patterns

To assess and document the spectrum of histological appearances of persistent swellings which occur at injection sites following vaccination or allergen desensitization. Fourteen cases were studied. Four overlapping histological reaction patterns were evident. Ten cases showed at least focal fibrosis, fat necrosis and a mixed inflammatory cell infiltrate mainly in the subcutis, giving rise to the features of a non-specific septal and lobular panniculitis. The appearance of three cases, in addition to the non-specific panniculitis pattern, also included prominent lymphoid follicles with germinal centres and a prominent perifollicular infiltrate resembling a lymphoma (pseudolymphoma pattern). A single case mimicked lupus profundus, with a perivascular and periadnexal infiltrate in the dermis and hyaline fat necrosis. Three cases showed a predominantly palisaded histiocytic infiltrate surrounding eosinophilic necrobiosis, in a pattern closely resembling deep granuloma annulare or rheumatoid nodule. The remaining case partly showed this appearance, but in combination with panniculitis, thus demonstrating an overlap of patterns. A common feature in all 14 cases was the focal presence of histiocytes with abundant violaceous granular cytoplasm. These were shown to contain aluminium on energy dispersive X-ray microanalysis. Persistent swellings at injections sites show a variety of overlapping patterns, which mimic other conditions. Identification of characteristic histiocytes with violaceous granular cytoplasm is the key distinctive feature allowing the correct diagnosis to be reached.

Subcutaneous Nodules at Injection Sites: Histopathological Pitfalls in Diagnosis

Subcutaneous swellings uncommonly occur at vaccination or desensitization injection sites and may present long after the procedure. Such lesions can show a range of histopathological appearances that are not well recognized, often leading to erroneous diagnoses. We describe the clinicopathological features of 13 cases (12 adults, 1 child) with subcutaneous swellings presenting at injection sites (upper arm n12, thigh n1). In the cases studied the histological appearances were varied, although predominantly the subcutis was involved. Six cases showed a mixed panniculitis with focal fat necrosis and fibrosis. Four cases demonstrated a pseudolymphomatous pattern, mimicking a B cell lymphoma. One case was reminiscent of lupus profundus and 3 other cases resembled deep granuloma annulare. Importantly, all cases contained histiocytes with violaceous granular cytoplasm, representing ingested aluminium salts employed for adsorption of antigens in the injection preparations. Energy dispersive x‐ray microanalysis in 8 cases confirmed a positive aluminium peak. Electron microscopy in 3 cases showed crystalline material in the histiocytes. In conclusion, the spectrum of histological appearances in so called aluminium granuloma can be misleading and it is important to identify the characteristic histiocytes of this condition, for otherwise erroneous diagnoses, with serious clinical implications, can follow.

Gastrointestinal stromal tumors (GIST): C-kit mutations, CD117 expression, differential diagnosis and targeted cancer therapy with Imatinib.

Gastrointestinal stromal tumors (GISTs) have been recognised as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract. They constitute the majority of gastrointestinal mesenchymal tumors. They are defined and diagnosed by the expression of a protooncogene protein called CD117 detected by immunohistochemistry. It is now believed that GISTs originate from gastrointestinal pacemaker cells known as interstitial cells of Cajal, that control gut motility or from a precursor of these cells. The identification of mutations mostly in exon 11 and to a lesser extent in exons 9 and 13 of the c-kit protooncogene coding for c-kit (CD117) in many GISTs, has resulted in a better understanding of their oncogenic mechanisms. The finding of remarkable antitumor effects of the molecular inhibitor, imatinib (Glivec trade mark ) in metastatic and inoperable GISTs, has necessitated accurate diagnosis of GISTs and their distinction from other gastrointestinal mesenchymal tumors. To achieve this, pathologists need to be familiar with the spectrum of histological appearances shown by GISTs and have a high index of suspicion for these tumors. This review summarises recent advances in knowledge regarding the histogenesis, pathology, molecular biology, genetics and differential diagnosis of GISTs and the basis for the novel targeted cancer therapy with imatinib.