Vulvar dermatoses-Can a pattern-based approach improve diagnostic yield?

BACKGROUND: Vulvar dermatoses (VD) pose a formidable challenge to clinicians and pathologists owing to various factors. The factors included are the histopathological heterogeneity of the vulva, moist and frictional environment, and the limited experience of gynecologists and general histopathologists in this field. To address this issue, the International Society for the Study of Vulvovaginal Disease (ISSVD) proposed a histopathological tissue reaction-based classification system for VD. Therefore, we attempted to study the utility of the 2006 ISSVD classification in reporting VD. We further evaluated if a dermatopathologist review could improve the diagnostic yield. MATERIALS AND METHODS: The vulvar biopsy reports (N = 106) were retrieved from histopathology case files, out of which benign non-infectious conditions (n = 55) were included in the study. The diagnosis retrieved from the case files was considered the initial diagnosis. Three dermatopathologists reviewed each biopsy, and a tissue reaction pattern/diagnosis was assigned as per ISSVD 2006, and this was considered a review diagnosis. The initial and review diagnoses were compared and analyzed. We further studied and analyzed the effect of the dermatopathologist's review on the diagnostic yield. RESULTS: The sclerotic pattern (34.6%) was the commonest tissue reaction pattern, followed by spongiotic (18%) and acanthotic patterns (14.5%) independently or in combination. The non-specific/descriptive report rate was significantly decreased following 2006 ISSVD and the dermatopathologist's review (83.6% vs.1.8%). CONCLUSION: Rendering tissue reaction patterns to vulvar biopsies will enable a comprehensive understanding of lesions and aid in clinically relevant reporting. In addition, dermatopathologists' review of difficult vulvar biopsies increases the diagnostic yield.

Differentiating Biliary Atresia From Idiopathic Neonatal Hepatitis: A Novel Keratin 7 Based Mathematical Approach on Liver Biopsies.

BACKGROUND AND AIMS: Differentiating biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is vital in routine pediatric practice. However, on liver biopsy, few cases offer a diagnostic challenge to discriminate these entities with certainty. Bile ductular reaction (DR), intermediate hepatobiliary cells (IHBC) and extra-portal ductules (EPD) indicate progenitor cell activation, as a response to various hepatic insults. The present study aims to quantify DR, IHBC and EPD by Keratin 7 (CK7) immunohistochemistry (IHC) in BA and INH and to devise a mathematical approach to better differentiate the two, especially in histologically equivocal cases. METHODS: A total of 98 cases were categorized on biopsy as BA, INH or equivocal histology, favoring BA or INH. CK7 DR mean, IHBC mean and EPD mean values were compared between BA and INH. A formula was derived to help distinguish these two entities, the cut-off value, sensitivity and specificity of which were determined by receiver operating characteristic (ROC) curve. This formula was applied and validated on histologically equivocal cases. RESULTS: Univariate logistic regression revealed significant difference between BA and INH with respect to CK7 DR and CK7 EPD mean (p < 0.001 in both); however, CK7 IHBC mean was not significant (p = 0.08). On multivariate logistic regression, only CK7 DR had significant impact on diagnosis (p < 0.001). A formula: (CK7 DR)2 + (CK7 EPD)/(CK7 IHBC) was derived to help distinguish BA from INH. Cut off value of 10.5 and above, determined by ROC curve, favored a diagnosis of BA (sensitivity= 93.4%, specificity= 94.6%). Histologically equivocal and discrepant cases could be correctly categorized using this formula. CONCLUSIONS: Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.

Myofibromatosis.

INTRODUCTION: Myofibromatosis is a distinctive mesenchymal disorder occurring predominantly in childhood, which on microscopy shows peripheral light areas of spindle cells and central cellular areas of primitive oval to spindle cells arranged around hemagiopercytomatous vessels. PDFGRB mutations in the familial and multifocal sporadic forms and SRF-RELA fusions in the cellular variants have been identified. The index case is being presented to discuss the clinico-pathological features, differential diagnosis, and management of the lesion. CASE PRESENTATION: An 11-year-old male presented with an infraorbital mass of 3 months duration. The mass was excised and microscopy revealed the morphological features of myofibroma with tram-track SMA immunopositivity. Nodular fasciitis and fibromatosis were the differentials considered. CONCLUSION: The SRF-RELA gene fusion may represent a subset that in the future may be used to differentiate these myofibromas/myopericytomas from the ACTB-GLI fusion myopericytomas, and PDGFRB may be used to perhaps separate out familial myofibromas from other myofibromas.

Non-malignant fibroblastic/myofibroblastic tumors in pediatric age group: Clues and pitfalls to the cytological diagnosis.

INTRODUCTION: Fibroblastic/myofibroblastic tumors constitute 12% of all pediatric soft tissue tumors with the majority of them belonging to the benign and intermediate prognostic categories. They are often misdiagnosed owing to their variable clinical presentation and unusual microscopic features. The diagnosis, specially cytological diagnosis of benign and intermediate categories is difficult due to paucity of cellular component and increased amount of extracellular matrix as compared to malignant ones. We hereby discuss the Fine needle aspiration cytology (FNAC) findings of non-malignant fibroblastic/myofibroblastic lesion in the pediatric age group encountered at our institute. METHODS: All the benign and intermediate fibroblastic/myofibroblastic/fibroadipocytic lesions (age 0-12 years) diagnosed on FNAC over a period of 3½ years (Jan 2016- July 2019), with availability of corresponding histopathology were included in the study. RESULTS: A total of seven pediatric benign and intermediate fibroblastic/myofibroblastic lesions with histopathological confirmation were identified which included Infantile digital fibromatosis (IDF) (n = 2), Lipofibromatosis (n = 1), Fibrous hamartoma of infancy (FHI) (n = 1), Fibromatosis colli (FC) (n = 2) and myofibroma/myofibromatosis (n = 1). FNAC smears were mainly paucicellular with presence of benign spindle shaped cells in a collagenous stroma common to almost all the cases. A few additional findings such as degenerated skeletal muscle fibres, muscle giant cells and mature adipose tissue were also present in some cases. CONCLUSION: Fibroblastic/myofibroblastic tumors although uncommon, form an important category that must be considered in the differential diagnosis of pediatric soft tissue tumors. FNAC cytology features when assessed in a proper clinical setting (specially the age and site of presentation) are helpful in suggesting probable preoperative diagnosis in these lesions.

Benign vascular anomalies: A transition from morphological to etiological classification.

The International Society for the Study of Vascular Anomalies (ISSVA) devised a multidisciplinary etiopathogenesis based approach to classify benign vascular anomalies into tumors and malformations. This classification scheme has major therapeutic and prognostic implications as treatment modalities differ for both the categories. Inappropriate usage of the term "hemangioma" for etiopathogenetically distinct entities is commonly seen in clinical practice leading to delivery of incorrect treatment to the patients. We aimed to study the histomorphological and immunohistochemical features of benign vascular anomalies for their precise histopathological classification. A total of 48 cases diagnosed over a period of 3.5 years were reviewed and reclassified into vascular tumors and malformations based on ISSVA classification and prototypical histopathological features. Biopsies were reviewed based on 5 histopathological criteria viz. endothelial morphology, mitotic activity, intralesional nerve bundles, intralesional inflammation, and prominent vessel type. A panel of GLUT-1, WT-1, and Ki-67 was performed in each case. Seven cases of infantile hemangioma, 4 cases each of non-involuting congenital hemangioma and pyogenic granuloma, and 33 cases of vascular malformations were diagnosed. Endothelial cell morphology (p < 0.001), mitotic activity (p < 0.001), and intralesional nerve bundles (p < 0.001) were found to be statistically significant in differentiating hemangioma from malformations. GLUT-1 (p < 0.001) and Ki-67 labeling index (p < 0.001) were useful to distinguish infantile hemangioma from vascular malformations. To conclude, the ISSVA classification of benign vascular anomalies can be reliably done on histopathology. However, every case must be interpreted in the light of clinical and radiological features.

Renal Pelvic Cholesteatoma: An Uncommon Finding in Children.

Renal cholesteatoma or keratinizing desquamative squamous metaplasia is infrequent in adults and rare in children. We report a case of renal cholesteatoma in a 4-year-old male child who was referred to us as a case of multiple renal calculi with hydronephrosis. We also discuss his management with a review of relevant literature.

Lipofibromatosis.

Introduction: Lipofibromatosis is a benign pediatric soft tissue tumor arising preferentially in the distal extremities. Histologically, the tumor shows abundant adipose tissue admixed with a spindle cell component, often concentrated in septal and perimysial locations. The index case is being presented to discuss the histopathological and immunohistochemical clues to differentiate it from other fibrofatty tumors of childhood.Case report: An 11-month-old male child presented with a slowly growing mass on the upper back. MRI findings were suggestive of an adipocytic tumor. Microscopy revealed a lesion composed of mature adipocytes and intervening fibrous bands with infiltration into the adjacent skeletal muscle, features of lipofibromatosis.Conclusion: Lipofibromatosis should be considered in the differential diagnosis of a pediatric fibrofatty tumor. Accurate diagnosis is essential for proper patient management as incomplete removal of the tumor may result in recurrence.

Childhood Phimosis Secondary to Lichen Sclerosus: Is There a Spatial Pattern of Histopathological Changes?

INTRODUCTION: The accurate histopathological diagnosis of the phimotic prepuce is indispensable because early diagnosis, treatment, and close follow-up are crucial in genital dermatosis such as lichen sclerosus (LS). This study analyzes the histopathological spectrum of childhood phimosis with special emphasis on LS. We also highlight a peculiar pattern of histopathological evolution in LS, prepuce. MATERIAL AND METHODS: The histopathology slides of all the pediatric preputial circumcision specimens performed for the indication of pathological phimosis (n = 43) during the study period (2012-2017) were analyzed. Eight histopathological features viz. hyperkeratosis, hypergranulosis, epidermal atrophy, acanthosis, dermoepidermal cleft, upper dermal edema and homogenization, mid dermal lymphocytic band, and interface dermatitis were studied in each case, separately in inner preputial surface, tip, and outer preputial surface. On the basis of evolution of the disease and histopathological features, the lesions of LS were classified into early, established, and advanced. RESULT: LS was found in 32 cases, whereas 11 cases showed nonspecific inflammation and fibrosis. The upper dermal homogenization (n = 29), dermoepidermal cleft (n = 28), and mid dermal band (n = 27) were the commonest histopathological changes. The established and advanced changes were confined to the inner preputial surface (n = 31), and the outer preputial skin surface was unaffected in all the cases. A peculiar histopathological evolution pattern was seen with established or advanced lesions, early lesion, and normal histology on the inner preputial surface, mucocutaneous junction, and outer preputial skin, respectively. CONCLUSIONS: LS is a common cause of childhood phimosis. It shows a peculiar histopathological evolution that mandates the thorough analysis of inner mucosal surface.

Dense Deposit Disease Mimicking a Renal Small Vessel Vasculitis.

Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0-3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature.

Microvessel density and Ki-67 labeling index in esthesioneuroblastoma: is there a prognostic role?

Esthesioneuroblastoma (ENB) is a malignant neuroectodermal tumor. Hyams grading has an established role in its prognostication. The importance of microvessel density (MVD) and Ki-67 labeling index (Ki-67 LI) is well studied in various tumors, but the same remains understated in ENB. The aims of the study were to estimate proliferation index and MVD in ENB and to correlate them with Hyams grade. Twenty-six ENB cases diagnosed over a period of 5 years were included. Hyams grade, MVD, and Ki-67 LI were evaluated for each of them. The cases were categorized as low (Hyams grades 1 and 2) and high (Hyams grades 3 and 4) grades. Microvessel density and Ki-67 LI were correlated with grade. The treatment response was analyzed in different grades. The commonest histologic grade was 4 (42%). The mean Ki-67 LI was 2%, 8.2%, 30.8%, and 40.5% and mean MVD was 81.67/mm(2), 37/mm(2), 24/mm(2), and 25.2/mm(2) in grades 1, 2, 3, and 4, respectively. A statistically significant correlation of grade with Ki-67 LI (P < .001) and MVD (P < .007) was noted. Hyams grade in ENB correlates well with treatment response. Ki-67 LI is an important prognostic factor in ENB. We propose a cutoff of 25% for Ki-67 LI to differentiate low- vs high-grade ENB, but larger studies are needed for validation. Contrary to epithelial tumors, there is a decrease in MVD with increasing grade in ENB.

Metastatic Adenocarcinoma of Prostate in a 28-Year-Old Male: The outcome is poor in young patients?

Prostate cancer is common in older patients. Rarity in younger population limits the study of natural history and prognosis in this population. Most of the published data has reported poor outcome in younger patients with metastatic prostate cancer. Here, we report a case of prostate cancer in 28-year-old male who presented with bone metastasis. After bilateral inguinal orchidectomy, he was started on anti-androgen therapy and received palliative radiotherapy for bone metastasis. There was only a slight decrease in prostate-specific antigen (PSA) level and pelvic disease post treatment. Subsequently, he was started on opioid analgesics (by World Health Organization, WHO, step ladder) in view of persistent pain. The index case is being presented for its rarity and probable poor outcome in young patients and to stress on the fact that the possibility of primary prostatic adenocarcinoma should be investigated in a male presenting with bone metastasis irrespective of the age.

Role of p40 and cytokeratin 5/6 in the differential diagnosis of sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is an epithelial neoplasm of sinonasal region which does not exhibit a squamous or glandular differentiation. The challenge in diagnosis of this entity is the rarity of the disease, the varying morphology of the tumor which leads to gamut of differential diagnosis and the paucity of consistent immunohistochemical markers except pancytokeratin. Forty-one cases of sinonasal epithelial neoplasm consisting of 11 cases of SNUC and 10 cases each of high-grade (grade 3 and 4) esthesioneuroblastoma, undifferentiated nasopharyngeal carcinoma, and poorly differentiated squamous cell carcinoma of the sinonasal region were analyzed for morphology and immunoexpression of CK5/6 and p40. It was found that SNUC did not exhibit immunohistochemical expression of p40 and CK 5/6, suggesting that these could be useful negative immune markers for diagnosis of SNUC.

Pulmonary mycoses diagnosed using exfoliative cytology: infection or colonization?

OBJECTIVES: Flexible bronchoscopy with exfoliative cytology is an important tool for the diagnosis of pulmonary fungal infections. The question of colonization versus true fungal infection is of critical importance. STUDY DESIGN: A 5-year retrospective analysis of all cases of pulmonary fungal infection diagnosed using exfoliative cytology was performed. Clinical, radiological, bronchoscopy and histopathology findings were recorded. RESULTS: A total of 69 cases of mycoses were retrieved. The most common fungal organism identified was Aspergillus followed by Candida and Pneumocystis. Most cases of Aspergillus and Candida in cytological specimens presented as a pulmonary mass or endobronchial growth and were diagnosed as carcinomas in biopsy specimens, thus representing colonization. All cases of Pneumocystis with bilateral ground glass infiltrates and cryptococcosis with parenchymal mass lesion in radiology represented true infection. Histoplasma was identified in pleural fluid from a known case of lung carcinoma. CONCLUSION: Aspergillus and Candida species are the most common fungal organisms. Most of these represent colonization of malignant growths. However, true fungal infections may also present as mass lesions and may masquerade malignancy clinically. Fluid cytological examination is an important diagnostic modality for pulmonary mycoses; however, it is important to correlate results with clinical, bronchoscopy and biopsy findings for accurate diagnosis and appropriate management.

Reliable Cerebrospinal Fluid Cytology and Immunocytochemistry Reporting over an Extended Period by the Addition of Aldehyde and Osmolyte-Based Preservative Solution.

INTRODUCTION: The cytological examination of cerebrospinal fluid (CSF) is an important investigation in the workup of various inflammatory, malignant, or traumatic disorders of the central nervous system. The cells in the CSF lyse and degenerate at a very fast rate owing to its low tonicity, buffering capacity, redox potential, and pH, making it crucial to examine it within 2 h of sampling. We have hereby designed an aliphatic aldehyde, osmolyte, metal halide, and a buffer-based solution which will preserve the cellular components of CSF for 48 h. METHODS: Thirty-nine CSF specimens were examined within 2 h of collection, and this reading was recorded as time zero reading. The CSF specimens were then divided into two tubes with (i) pre-servative:CSF ratio of 1:5; and (ii) no preservative. Total and differential leukocyte counts and immunocytochemistry were performed on the paired specimens at 24 h and 48 h and were compared with the readings at zero hours. RESULTS: The preservative-containing CSF showed significantly higher cellularity than the undiluted samples at 24 h and 48 h (p < 0.001). Median cell counts observed in the preservative-containing CSF were 5 times and 12 times higher than in the undiluted CSF. Neutrophils, lymphocytes, and RBCs showed immunopositivity for MPO, CD45, and GLUT-1 at both time intervals. CONCLUSION: Adding the prepared preservative solution to CSF in the ratio of 1:5 can optimally preserve the CSF cells for absolute and differential quantitation, morphological assessment, and immunological testing at a later date.