Mucoepidermoid carcinoma-a rare salivary gland-type tumor of the breast: are we dealing with primary or secondary?-a case report and literature review.

Background: Salivary gland-like tumors are extremely unusual in the breast, and their histology is very similar to primary salivary gland neoplasms. Mucoepidermoid carcinoma (MEC), a common salivary gland tumor, displays an infrequent occurrence in the breast, accounting for a mere 0.2-0.3% incidence. Given its rarity, it is critical to accurately distinguish it from metastatic cases before diagnosing it as a primary breast MEC for appropriate treatment. Currently, there is no consensus on the treatment of MEC, and there is a paucity of literature highlighting the ideal treatment modality, especially for estrogen receptor (ER)-positive cancers. Therefore, the aim of our case report was to underscore the diagnostic process, surgical and adjunctive treatments for our patient with ER-positive, progesterone receptor (PR)-negative and human epidermal growth factor receptor 2 (HER2)-negative MEC while also conducting a literature review to contribute to the limited existing data. Case Description: A 67-year-old African American woman presented with a lobulated 3.1-cm left breast mass on mammography, for which she underwent ultrasound-guided core needle biopsy that revealed invasive carcinoma with squamous differentiation. The carcinoma was ER-positive, PR-negative and HER2-negative. Subsequently, she underwent a lumpectomy with sentinel lymph node biopsy. Her final pathology revealed an intermediate-grade MEC with negative lymph nodes. She had a past medical history of benign salivary gland tumor, as well as a family history of BReast CAncer gene 1 (BRCA1)-associated breast cancer in her daughter. Conclusions: MEC of the breast is a rare tumor with a relatively favorable overall prognosis. The early and precise diagnosis of this condition plays a pivotal role in formulating effective treatment strategies and ensuring positive survival rates. Nonetheless, future studies are recommended to further explore the role of surgical approaches and adjuvant therapy to improve treatment outcomes.

Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

CONTEXT.­: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.­: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.­: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Clinical, histological features, and predictors of relapse in patients with idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis is a benign, inflammatory disease of breasts characterized by non-caseating granulomas. Our study aims to identify distinguishing clinical and histopathological features of relapsing disease compared to those in complete remission. We queried databases at our institution (1990-2021) to include females ≥18 years with biopsy-proven diagnosis of idiopathic granulomatous mastitis, excluding patients with breast cancer, lymphoproliferative disorders, solid organ malignancy, foreign body reaction in breast, plasma cell mastitis, and ductal ectasia. Remission was defined as a 3-month period without recurrence of symptoms or imaging findings. Relapse was defined as recurrence after 3 months of remission. Clinical and histopathological features were compared using 2-sample t tests and chi-squared tests. Of the 27 patients that met our inclusion criteria, the mean age at diagnosis was 35.8 years (± standard deviation 9.4 years) with a mean body mass index of 31.7 kg/m2 (± standard deviation 6.7 kg/m2). 11 (41%) were Hispanic, 25 (93%) had at least one previous full-term pregnancy prior to diagnosis and 8 (30%) were on oral contraceptives. Remission was seen in 18 patients (66%) and 9 (33%) had relapse. Six of these patients received steroids after antibiotics, while 5 patients received methotrexate. Three (33%) patients with relapse and 14 (77%) with remission, had abscess formation confirmed on histopathology (P = .04). Patients with remission had a higher number of abscesses on histopathology and history of oral contraceptive use was associated with more relapse. By identifying key clinical and histopathological findings in this population may guide prognosis and treatment of these patients.

Long-term immunosuppression and multiple transplants predispose systemic lupus erythematosus patients with cytopenias to hematologic malignancies.

ABSTRACT: Cytopenias in systemic lupus erythematosus (SLE) require clinical and laboratory workup and bone marrow (BM) examination to determine the cause and for appropriate patient management. Common causes include an increase in SLE activity, immune-mediated hemolysis, iron deficiency, antiphospholipid antibody syndrome, infection, or the effect of medications. We retrospectively evaluated the clinical and laboratory findings of patients with SLE and cytopenias who had undergone BM studies to determine the indicators of malignancy.We retrospectively reviewed medical records of patients with SLE who presented with cytopenias for their disease course, medications, laboratory parameters and documented the spectrum of morphological changes in BM including CD34 expression.Twenty patients with SLE had undergone BM biopsy for evaluation of cytopenias. 14/20 (70%) of the patients had reactive BM, and the rest had hematologic malignancies involving the BM. Of these 14 patients, 8 had hypocellular marrow with loss of precursor cells (low CD34), 4 had left shift in myeloid lineage, 3 had serous atrophy, and 1had multilineage dysplasia. The 6 patients with hematologic malignancies included 2 with diffuse large B cell lymphoma, and one each of natural killer/T cell lymphoma, post-transplant lymphoproliferative disorder, Hodgkin lymphoma, and myelodysplastic syndrome evolving to acute myelogenous leukemia. The presence of autoantibodies, SLE activity, and lupus nephritis were comparable in patients with and without neoplasia. However, the duration of the use of multiple immunosuppressants, years since renal transplant (22 vs 10), multiple transplants, and the presence of other autoimmune diseases were greater in those with neoplasia. Two of the 14 patients with non-neoplastic BM and 1 with the neoplastic BM had nonhematological malignancy.Clinical and laboratory findings, the number of transplants, and the use of immunosuppressive agents can guide physicians to identify patients with a higher risk of developing hematologic malignancy. BM findings of cytopenia in SLE are often due to increased disease activity causing global cell death and dysmaturation. SLE patients presenting with cytopenias, with a history of long-term exposure to immunosuppressive drugs, should be regularly screened for hematologic and nonhematologic malignancies.

Pathologic reporting practices for breast cancer specimens after neoadjuvant chemotherapy-a survey of pathologists in academic institutions across the United States.

Neoadjuvant chemotherapy is increasingly being used to treat primary invasive breast carcinoma. Response to neoadjuvant chemotherapy is an important determinant of prognosis. A multidisciplinary group published recommendations for standardization of pathologic reporting of postneoadjuvant chemotherapy specimens. Based on these recommendations, we sent a survey to 26 pathologists currently practicing breast pathology in academic centers across the United States. The survey consisted of six questions with yes/no answers. The pathologists were encouraged to add comments. We received responses from 23 breast pathologists from 19 centers. The questions and responses were as follows: 1. Do you grade tumors after neoadjuvant chemotherapy?-17 (74%) responded yes and 6 (26%) responded no. 2. Do you routinely repeat hormone receptors, HER2/Neu results after neoadjuvant chemotherapy?-15 (65%) responded yes and 8 (35%) responded no. 3. If there are features of tumor regression/tumor bed at the margin but no actual tumor at the margin do you report this?-11 (48%) responded yes and 8 (35%) responded no and 4 (17%) reported a variable practice. 4. Do you report number of nodes with fibrosis/changes of regression?-17 (74%) responded yes and 6 (26%) responded no. 5. Do you report residual cancer burden score on your report or at least provide information on your report so clinicians can calculate residual cancer burden?-17 (74%) responded yes and 6 (26%) responded no. 6. Do you have a specific synoptic for cases after neoadjuvant chemotherapy?-5 (22%) responded yes and 18 (78%) responded no. The major reasons provided for nonadherence to recommended guidelines included pathologists were unaware of prognostic importance of providing the information, reporting practices were clinician driven and some pathologists were unaware of the recommendation. We document that academic breast pathology practices show significant variability in reporting of postneoadjuvant chemotherapy cases. We document barriers to standard practice and provide recommendations we hope will contribute to a more uniform reporting practice for these complex specimens.

Analysis of Causes of Death as Determined at Autopsy in a Single Institute, The Grant Medical College and Sir J. J. Hospital, Mumbai, India, Between 1884 and 1966: A Retrospective Analysis of 13 024 Autopsies in Adults.

CONTEXT.­: Grant Medical College and Sir J. J. Hospital, Mumbai (India), have a long tradition of clinical autopsies, wherein autopsy records have existed since 1884. The old autopsy records from 1884 to 1966 were discovered during a refurbishing drive of the pathology department in 2007. OBJECTIVE.­: To know the relative causes of deaths in Sir J. J. Hospital Mumbai from 1884 through 1966. To determine the rate of antemortem and postmortem discrepancies in the prehistology and posthistology era. DESIGN.­: The reports of clinical autopsies in the archives of the Department of Pathology from January 1884 to December 1966 were reviewed. Data such as sex, age, and clinical and autopsy diagnoses were collected, based on the autopsy records of 13 024 patients. RESULTS.­: Of 13 024 patients, 10 197 (78%) were male and 2827 (22%) were female. Most deaths (55%) involved individuals ages 21 to 40 years. Infections were the cause of death in 7281 of 13 024 patients (56%), followed by cardiovascular diseases in 2138 (16%) and neoplasms in 963 (7%). The overall disagreement between clinical diagnoses and postmortem findings was 4105 of 13 024 patients (31%). Discrepancy between antemortem and postmortem diagnoses in the prehistology era (before 1950) was found in 3053 of 8951 patients (34%), whereas in the posthistology era (after 1950), discrepancy was found in 1019 of 4073 patients (25%). CONCLUSIONS.­: Historical collections provide baseline data against which modern observations can be compared. Such collections also offer a window on the past and often provide a less biased account of events. Historical collections of museum materials such as ours are valuable because they can serve as potential biorepository materials to facilitate future research. Apart from providing reliable data on the occurrence of diseases, the autopsy has an important role in providing information about conditions that are no longer prevalent. Medical institutes possessing old autopsy records, wet specimens, paraffin blocks, and slides should preserve such historical collections.

Loss of Placental P-Glycoprotein May Be a Common Pathophysiologic Pathway for First Trimester Spontaneous Miscarriages.

INTRODUCTION: P-glycoprotein the highly conserved mammalian adenosine triphosphate-binding cassette transmembrane multidrug protein transporter is involved in peri-implantation events and fetal placental development. Greater expression in early versus late pregnancy and localization in both syncytio- and cytotrophoblast indicate that P-glycoprotein transports substances across the uterine epithelium during early pregnancy and protects the conceptus from toxic substances during implantation and early embryogenesis. We hypothesized that P-glycoprotein is involved in the physiologic maintenance of early pregnancy and that P-glycoprotein dysregulation may be involved in early pregnancy pathologies. METHODS: First trimester dilation and curettage specimens were selected retrospectively from the archives of the Department of Pathology from spontaneous miscarriages (n = 36) and elective termination of pregnancy (n = 20). Two P-glycoprotein specific monoclonal antibodies JSB1and C219 were used on formalin-fixed, paraffin-embedded 5µ tissue sections. The location, intensity, and percentage of P-glycoprotein chorionic villous immunostaining were semiquantitated. RESULTS: Spontaneous miscarriages demonstrated absence or significant reduction in P-glycoprotein compared to elective terminations; 75% (27/36) showed total absence of P-glycoprotein, 19% (7/36) showed only rare villi with discontinuous immunostaining, and 6% (2/36) showed weak immunostaining. In contrast, 90% of elective terminations (18/20) showed positive immunostaining for P-glycoprotein and only 10% (2/20) showed loss of P-glycoprotein expression (P < .0001). DISCUSSION: We report a dramatic loss/decrease of P-glycoprotein in first trimester spontaneous miscarriages. This finding in conjunction with the known high expression of P-glycoprotein in normal first trimester placental tissues suggests an important role of P-glycoprotein in the maintenance of early pregnancy.

Loss of PTEN and Increased pAKT Expression Distinguishes Aggressive Low-grade Neuroendocrine Tumors.

A major problem in neuroendocrine pathology is the identification and separation of aggressive low-grade neuroendocrine tumors (LGNETs) from those with a benign or more indolent behavior. Presently there are no known morphologic or molecular parameters which can predict how localized LGNETs will behave. The phosphatase and tensin homolog (PTEN) gene negatively regulates the PI3K-AKT-mTOR pathway and inhibits neoplastic cell survival and proliferation and has recently been identified as a neuroendocrine tumor differentiation marker. We hypothesized loss of PTEN may also identify LGNETs that demonstrate aggressive behavior. We studied PTEN and pAKT expression in 18 LGNETs using specific monoclonal antibodies. Follow up was obtained for a minimum of five years on all patients. 8/18 cases had strong PTEN expression and showed no evidence of disease on >5 years follow-up. 10 cases demonstrated loss of PTEN expression; 9/10 had positive pAKT expression, and 7/9 had recurrence and/or metastases. Lung and appendiceal LGNETs uniformly had high PTEN expression and a markedly better prognosis than their gastroenteropancreatic (GEP) counterparts. Loss of PTEN correlated significantly with the positive expression of pAKT (P=0.0027) and aggressive behavior of LGNETs (p=0.0002). Loss of PTEN and increased pAKT correlated with the metastatic potential of LGNETs (p=0.0011 and 0.0248 respectively). Loss of PTEN and increased pAKT expression distinguishes aggressive LGNETs from those with more indolent behavior.

Black race and distant recurrence after neoadjuvant or adjuvant chemotherapy in breast cancer.

Black race compared to white race is associated with more advanced stage and biologically aggressive breast cancer. Consequently, black patients are more frequently treated with neoadjuvant chemotherapy (NAC) than white patients. However, it is unclear how distant recurrence-free survival (DRFS) of black patients treated with NAC, compares to DRFS of black patients treated with adjuvant chemotherapy (AC). We evaluated the association between race, distant recurrence, and type of chemotherapy (AC or NAC) in localized or locally advanced breast cancer. We evaluated DRFS in 807 patients, including 473 black, 252 white, 56 Hispanic, and 26 women of other or mixed race. The association between AC or NAC and DRFS was examined using multivariate Cox proportional hazard models that included race, age, stage, estrogen receptor (ER) and triple negative (TN) status. When the black and white subjects were pooled for the analysis the features associated with worse DRFS included stage III disease and age < 50 years, but not ER-negative disease, TN disease, the use of NAC, or black race. However, in the analysis stratified by race NAC was associated with worse DRFS compared to AC in black (HR 2.70; 95% CI 1.73-4.22; p < 0.0001), but not in white women (HR 1.29, 95% CI 0.56-2.95; p = 0.36). Black patients treated with NAC had worse DRFS than black patients treated with AC, or white patients treated with either NAC or AC. These findings need to be validated in a large-scale observational study and the effect of NAC on the breast cancer microenvironment in black women needs to be further evaluated.

IgG4-Related Disease of the Punctum and Canaliculus.

A 60-year-old man with no past medical history presented with a 14-month history of a painless medial left lower eyelid mass causing mechanical ectropion and discharge from the inferior punctum. Excisional biopsy was performed via a transconjunctival canaliculotomy and histopathology revealed a dense plasma cell infiltrate with IgG4+ plasma cells >100/high power field and an IgG4/IgG ratio of 65%. Serum IgG4 was found to be elevated at 224 mg/dl (reference range: 4-86 mg/dl). Systemic work up with PET CT was negative. The patient's signs and symptoms all resolved without medical treatment and he remains disease free 24 months following surgery. A single case of IgG4 disease of the nasolacrimal duct has been reported, but to the authors' knowledge, disease involving the proximal nasolacrimal outflow system has yet to be described. The authors herein report a case of IgG4-related disease involving the punctum and canaliculus.

Pathology of thyroid in acquired immunodeficiency syndrome.

BACKGROUND: The course of human immunodeficiency virus infection and the acquired immunodeficiency syndrome can be complicated by a variety of endocrine abnormalities, including abnormalities of thyroid gland. MATERIALS AND METHODS: This study was designed to understand the spectrum of pathology of thyroid in Indian patients with AIDS. The present study describes the findings of retrospective autopsy findings of 158 patients with AIDS which revealed infectious diseases from a time period before the use of highly active antiretroviral regimen. RESULTS: A wide range of bacterial, fungal, and viral infections were observed. Tuberculosis was recorded in 14 (09%) patients, Cryptococcus neoformans in 11 (7%) patients and cytomegalovirus in 3 (2%) patients. Hashimoto's thyroiditis and lymphocytic thyroiditis were seen in 02 (01%) patients each. One patient had dual infection comprising of tuberculosis and cytomegalovirus infection. The other microscopic findings observed were goiter (2 patients), interstitial fibrosis in thyroid (7 patients), and calcification in thyroid (8 patients). CONCLUSIONS: Abnormalities of thyroid are uncommon findings in patients with HIV infection however several case reports of thyroid involvement by infectious agents and neoplasm are described in these patients; hence patients with HIV infection should be closely followed up for development of goiter or abnormalities of thyroid functions.

Pathologic lesions in children with acquired immunodeficiency syndrome an autopsy study of 11 cases from Mumbai, India.

BACKGROUND: Human immunodeficiency virus (HIV) infection in India has now been prevalent over three decades, and an increasing number of children are being affected with HIV. The spectrum of pathologic lesions in children with acquired immunodeficiency syndrome (AIDS) in India has not been well described. MATERIALS AND METHODS: A review of systematically conducted autopsies of 11 (10 boys and 1 girl) children with AIDS is presented. RESULTS: The mode of HIV transmission in 6 children was vertical; in one it was blood transfusion and in 4 children route was presumably vertical as these were children of orphanage. The clinical manifestations were failure to thrive; 9 children, persistent gastroenteritis; 8, recurrent fever; 5, bacterial infections; 5, hepatosplenomegaly; 5, candidiasis; 1, scabies; 1, skin rash; 2, tuberculous (TB) meningitis; 1 and paraplegia; in 1 child. The spectrum of pathologic lesions observed were precocious involution in thymus in 3 and dysinvolution in 2 cases. Infectious diseases comprised of TB; 4 cases, cytomegalovirus infection (CMV) 4; bacterial pneumonia and meningitis; 7, and esophageal candidiasis in 2 cases. Dual or multiple infections were observed in 9 (82%) cases; these comprised of two lesions in 2, three lesions in 2, four lesions in 4, and five lesions in 1 case. TB, bacterial pneumonia, meningitis, and CMV infection are the most frequent causes of death in children with AIDS. Vascular lesions showing features of arteriopathy were observed in 5 cases and brain in one case showed non-Hodgkin's lymphoma. CONCLUSIONS: This study provides a better insight into the spectrum of pathologic lesions in children with AIDS in India. TB and CMV infection has been found to be the most prevalent infection in our children.

Metastatic Small Cell Carcinoma of the Lung: An Unusual Cause of Acute Fulminant Hepatic Failure.

For patients with acute fulminant liver failure, imaging and histopathologic studies are indicated to reveal the underlying etiology, and metastatic small cell carcinoma should be included in the clinical differential diagnosis when appropriate.

Cutaneous myxoma: an important clue to Carney complex.

A 22-year-old male became unconscious and was found to have left-sided weakness and facial asymmetry. Previously, he had up to 35 excisions for subcutaneous swellings all over the body, commencing at age 6 years. Examination revealed small nodular skin lesions on the neck, the eyelid and hard palate. Two-dimensional echocardiography showed two left atrial masses. Histopathological examination of the subcutaneous lesions showed cutaneous myxomas with a prominent epithelial component. The left atrial masses were also myxomas. The case attempts to highlight the importance of histopathological examination of subcutaneous swellings. Cutaneous and subcutaneous manifestations, including cutaneous myxomas, are among the earliest presentations in Carney's complex and may herald potentially fatal cardiac myxoma. The prominent epithelial component in cutaneous myxomas may be confusing and cause diagnostic difficulties.

Coexistent lymphoma with tuberculosis and Kaposi's sarcoma with tuberculosis occurring in lymph node in patients with AIDS: a report of two cases.

Although there have been a few reports of simultaneous infections and neoplasm in patients with acquired immune deficiency syndrome, no reports of coexistent lymphoma with tuberculosis and Kaposi's sarcoma with tuberculosis occurring in the same lymph node have been described. In this article, we describe coexistent lymphoma with tuberculosis in one case and Kaposi's sarcoma with tuberculosis in another case of human immune deficiency virus-infected individuals.