Systematic Review and Meta-Analysis of the Diagnostic Accuracy of the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy in Diagnosing Breast Cancer.

OBJECTIVES: The primary objective is to determine the accuracy of fine-needle aspiration biopsy (FNAB) in breast lesions reported according to the International Academy of Cytology (IAC) Yokohama system for reporting breast FNAB. The participants include any patient presenting with any breast lesion found suitable for FNAB. The target condition was breast cancer. The secondary objective was to study the proportion of inadequate FNAB in the selected studies. METHODS: PubMed/MEDLINE and Embase were searched for studies having all the following key search terms: Breast AND FNAB AND Diagnostic Accuracy published in the time frame of 2017 to May 16, 2022. The Cochrane and PROSPERO databases, citations of selected articles and articles citing the selected articles were also searched. Studies assessing the diagnostic accuracy of breast FNAB in diagnosing breast cancer, which had at least 75 subjects (and at least 20 subjects each in the benign and malignant FNAB groups), were selected. The reference standard was histopathology (or adequate clinical follow-up for benign disease). Studies were screened independently by two researchers, with a consensus reached among the authors in cases of conflict. The risk of bias and applicability were assessed using the QUADAS-2 tool. Sensitivity and specificity at each diagnostic cut-off were assessed by bivariate generalized linear mixed-model meta-analysis. The area under the receiver operating characteristics curve (AUC) and inadequacy rate were assessed by random-effects meta-analysis. The confidence intervals of sensitivity, specificity, and AUC were examined against a value of 0.95. RESULTS: Twenty-two studies, all of which were cross-sectional single-gate studies, were selected with a total of 10,886 subjects with a primary breast lesion having concurrent FNAB and reference standard reports. Sensitivity and specificity, with 95% confidence intervals, were 0.978 [0.968, 0.985] and 0.832 [0.76, 0.886] for the diagnostic cut-off of "Atypical considered positive for malignancy," 0.916 [0.892, 0.935] and 0.983 [0.97, 0.99] for the cut-off of "Suspicious of Malignancy considered positive," and 0.763 [0.706, 0.812] and 0.999 [0.994, 1] for the cut-off of "Malignant considered positive." The overall AUC was 0.975 [0.962, 0.984]. FNAB sampling without imaging guidance was associated with lower inadequacy. DISCUSSION: There is strong evidence that the overall accuracy, sensitivity for "Atypical category considered positive" and specificity when "Suspicious or Malignant categories are considered positive" of FNAB are high when using the categories of the IAC Yokohama Reporting System, demonstrating the usefulness of FNAB in diagnosing breast cancer.

IgG4-Related Pancreato-Biliary Disease in the Disguise of Malignancy.

The Immunoglobulin G4-related disease (IgG4-RD) is a multisystem inflammatory condition. Pancreaticobiliary manifestations often present as mass lesions that mimic malignancies. The diagnosis is confirmed by histopathological examination, that shows lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and positive immunohistochemistry for IgG4. We encountered 3 such patients in a tertiary care hospital in India. Two patients presented with obstructive jaundice and the third with pain abdomen. They had resectable lesions involving the pancreatic head, the right hepatic duct, and gallbladder fundus, respectively, on imaging. Tumor markers were not significantly elevated in any of them. All 3 patients underwent radical surgeries, suspecting malignancy. Surgical specimens showed typical features of IgG4-RD on histomorphology. Serum IgG4 level was elevated in first 2 patients but was normal in sclerosing cholecystitis patient. To conclude, IgG4-RD is a malignant mimicker; hence, on clinical suspicion, liberal attempts for tissue diagnosis may avoid radical surgeries.

Porokeratotic Variant of Lichen Planus.

A 44-year-old woman presented with mildly itchy, brownish-black plaques for the last 2 years. The lesions first appeared on the upper back, followed by involvement of the face and upper arms within 4-5 months. Individual lesions began as small papules that gradually evolved into small, annular, and barely palpable plaques. There were no systemic complaints, photosensitivity, or history of intake of prolonged medication. Cutaneous examination revealed multiple, well-demarcated, and hyperpigmented oval to round plaques on the photo-exposed area, including the face, bilaterally on arms, and upper trunk, measuring about 1 × 1-3 × 3 cm2 in size (Figures 1A and 1B). Dermatoscopic examination established rolled-out, thread, double-marginated border with central atrophy with a brownish reticular background. Multiple brownish to black globules and dark lacunae were also observed (Figures 1C and 1D). No Wickham's striae were viewed. Combination of clinical presentation with dermatoscopic findings indicated a provisional clinical diagnosis of disseminated superficial porokeratosis. Biopsy performed on the upper back revealed hyperkeratotic epidermis with mild lymphocytic exocytosis and spongiosis with pigmentary incontinence. The coronoid lamina was not revealed in any of the pathologic sections examined, including further deeper sections and in a repeat biopsy. Clinical morphology, dermatoscopic features, and pathology were considered compatible with the diagnosis of porokeratotic variant of lichen planus (LP). The patient was counseled and started on topical steroids (fluticasone). She is on regular follow-up.

Bilateral sixth cranial nerve palsy, the first presenting feature of hemorrhagic apoplexy of pituitary macroadenoma: A case report.

INTRODUCTION AND IMPORTANCE: We report on apoplexy of undiagnosed pituitary macroadenoma presenting as sudden onset bilateral sixth nerve palsy. CASE PRESENTATION: A 36-year-old male patient presented with a complaint of sudden onset diplopia for one week associated with chronic headache for two years. On further investigations, isolated bilateral sixth cranial nerve palsy was found to cause diplopia in lateral gaze and at distance. Magnetic resonance imaging of the brain showed a well-defined lobulated mass of 19 × 22 × 24 mm in the sellar and suprasellar region with hemorrhage, compressing optic chiasma superiorly with extension into the superior cavernous sinus compartment on the left side. The neurosurgery team excised the tumour through an endoscopic endonasal transsphenoidal approach. Abducens nerve palsy recovered within one week. CLINICAL DISCUSSION: In our case diplopia due to bilateral sixth cranial nerve palsy was the first clinical presentation of hemorrhagic apoplexy of pituitary macroadenoma which is a potentially life-threatening condition. There was no other significant ocular symptoms. High index of suspicion, prompt diagnosis and multidisciplinary team management resulted into favourable outcome. CONCLUSION: Sudden onset diplopia and isolated bilateral sixth nerve palsy should be added to the spectrum of clinical presentations of hemorrhagic apoplexy of previously undiagnosed pituitary macroadenoma.

Visceral leishmaniasis masquerading as drug-induced pancytopenia in myasthenia gravis.

Visceral leishmaniasis (VL), also known as kala-azar (black fever in Hindi), is a disease primarily caused by Leishmania donovani. The most important clinical manifestation of visceral leishmaniasis is fever. Nonspecific laboratory findings of visceral leishmaniasis include anemia, neutropenia, eosinopenia, and thrombocytopenia. Definitive diagnosis of visceral leishmaniasis requires the demonstration of either parasite by smear or tissue by culture (usually bone marrow or spleen). Myasthenia gravis is an autoimmune disease caused by antibodies to acetylcholine receptors in the post-junctional membrane of the neuromuscular junction. It typically presents with fatigable muscle weakness without any sensory or brain involvement. It is usually treated with corticosteroids and immunosuppressants like azathioprine. Here we encountered a confirmed case of myasthenia gravis on azathioprine with pancytopenia. While working up to evaluate pancytopenia, bone marrow examination revealed presence of Donovan bodies and the patient showed good response to liposomal amphotericin-B. In retrospect, a case of myasthenia gravis, who presented with pancytopenia presumably drug-induced, was found to have visceral leishmaniasis.

Gastrointestinal Biopsies for Evaluation of Acute Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Patients.

Graft-versus-host disease (GVHD) is the major complication post hematopoeitic stem cell transplantation (HSCT) causing significant morbidity and mortality. Colonic biopsies were performed in 25 post HSCT patients presenting the diarrhea for diagnosis of acute graft versus host disease (A-GVHD). The present study was undertaken to evaluate and illustrate histomorphological features of A-GVHD in GI biopsies and to grade them. Histopathological features of gastrointestinal biopsies from 25 allogeneic HSCT patients having clinical suspicion of A-GVHD were evaluated and compared with colonic biopsies from negative controls. A-GVHD was observed in 17 cases, CMV colitis was present in 3 cases and one case had herpes simplex infection diagnosed in conjunction with serological findings. A-GVHD was graded as grade 1 and 2 in 10 cases and grade 3 and 4 in 7 cases. Apoptosis of crypt epithelial cells was the cardinal feature for diagnosis. Grade 1 and grade 2 A-GVHD cases showed crypt apoptosis in all cases as well as pericryptal apoptosis in lamina propria in many cases. Occasional crypt loss was seen in grade 2 GVHD. Inflammatory infiltrate was composed of lymphocytes and plasma cells. Neutrophils were inconspicuous. Grade 3 and grade 4 A-GVHD cases showed contiguous areas of multiple crypt loss and ulceration with inflammatory infiltrate predominantly composed of lymphocytes and plasma cells, but neutrophils were more prominent than in grade 1 and 2 A-GVHD. Apoptosis of crypt epithelial cells was present in all grade 3 &4 cases except one case. CMV cases were diagnosed by CMV inclusions and IHC stain. Several factors including drug-induced side effects and infections can cause difficulty in histologic interpretation of gastrointestinal biopsies for GVHD. Proper histomorphological interpretation of intestinal A-GVHD is critical for clinical management. A-GVHD is treated with immunosuppression which may worsen infective condition, if present.

Mixed adenoneuroendocrine carcinoma of the gallbladder, histopathological features.

An unusual case of mixed adenoneuroendocrine carcinoma is described which posed a diagnostic challenge in view of neuroendocrine component mimicking signet ring cells of adenocarcinoma. Diagnostic criteria for these mixed tumors, their histogenesis and treatment modalities are highlighted.