Michael Covinsky

Serum Albumin Concentration and Clinical Assessments of Nutritional Status in Hospitalized Older People: Different Sides of Different Coins?

Malnutrition is common in hospitalized older people, and some have advocated routine nutritional screening. Serum albumin and clinically based measures such as the Subjective Global Assessment (SGA) are two potential methods of assessing nutritional status in hospitalized older people. Although both measures are strongly associated with prognosis, it is not clear whether they measure similar or different clinical constructs. Our goal was to assess the degree of clinical concordance between these measures.

The Impact of Declining Clinical Autopsy: Need for Revised Healthcare Policy

In Western countries, autopsy rates for patients deceased in hospitals have dropped to record lows, while the average frequency of major errors in clinical diagnoses has more than doubled during the same time period. Meanwhile, the Institute of Medicine and the U.S. Department of Health and Human Services have called attention to the high frequency of errors affecting patient safety, bringing the issue of public safety to the forefront of public health concerns. Although autopsies represent a vital tool for the acquisition of new medical knowledge and for medical quality assurance, health care professionals, insurers, and politicians apparently have not chosen the right approach to solve the problem of declining autopsy rates. The present article reviews the current status of clinical autopsies and addresses causes and consequences of their neglect and appeal the urgent need to revise the policy for clinical autopsy.

Desmoplastic Nested Spindle Cell Tumor of Liver: Report of Four Cases of a Proposed New Entity

Abstract:We describe a distinctive tumor of the liver in four children composed of nested spindled and epithelioid cells with extensive desmoplasia that we have termed “desmoplastic nested spindle cell tumor of the liver.” All four patients were previously healthy. One patient had a presumptive diagnosis of hepatic hemangioma 11 years prior to presentation. Grossly, the tumors were well circumscribed, lobular white masses, ranging from 2.8 to 15 cm in diameter. These tumors were characterized by the presence of cohesive nests of plump, bland spindle cells arranged in short fascicles with an accompanying desmoplastic stroma. Epithelioid areas ranging from palisading epithelioid cells at the periphery of some nests to pseudoglandular and polygonal cells with intercellular bridges were invariably present. Mitotic activity was low. Calcification and ossification were present. Non-neoplastic bile ducts and hepatic elements were seen both within and surrounding the tumor cell nests. Each tumor displayed cytoplasmic reactivity for vimentin, pan-cytokeratin, CD57, and nuclear staining for WT1. Neuroendocrine markers were negative. Ultrastructurally, the tumor cells showed focally well-developed cell junctions, basal lamina, and few cytoplasmic organelles. All tumors were confined to the liver and were resected without complication. Two patients received postoperative adjuvant therapy for presumed hepatoblastoma. The patients are doing well without recurrence at 7.5 years, 7 years, 5 years, and 8 months post-surgery. The morphologic appearance and immunohistochemical profile of these lesions are unique in our experience and represent a new category of pediatric liver tumor.

Clear Cell Sarcoma of Kidney: Morphoproteomic Analysis Reveals Genomic Correlates and Therapeutic Options

We used the morphoproteomic approach to analyze clear cell sarcoma of kidney (CCSK), a rare pediatric renal tumor, for which the exact pathogenesis and reliable diagnostic markers remain inexplicable. The tumor, currently being treated with chemotherapy and radiation therapy before or after radical nephrectomy, has demonstrated improved survival rates after introduction of doxorubicin. Three cases of CCSK were studied. We attempted to decipher the possible pathological mechanisms involved in CCSK and to explore the therapeutic targets and plausible less-toxic chemotherapeutic agents. We propose that eye lin D1 may be a central molecule in the pathogenesis of CCSK, driven mainly by the sonic hedgehog and the nuclear factor–kappa B pathways and secondarily by the mammalian target of rapamycin complex mTORC2/PI3K/Akt pathway, heat shock protein 90, and possibly phospholipase D1. Inclusion of relatively less toxic but effective therapies in the form of statins, 13-cis retinoic acid, curcumin, and 17-AAG in the combinatorial treatment strategies, which can target the involved subcellular pathways, may be considered.

First Neonatal Demise with Travel-Associated Zika Virus Infection in the United States of America

Zika virus is increasingly recognized as a fetal pathogen worldwide. We describe the first case of neonatal demise with travel-associated Zika virus infection in the United States of America, including a novel prenatal ultrasound finding. A young Latina presented to our health care system in Southeast Texas for prenatal care at 23 weeks of gestation. Fetal Dandy–Walker malformation, asymmetric cerebral ventriculomegaly, single umbilical artery, hypoechoic fetal knee, dorsal foot edema, and mild polyhydramnios were noted upon initial screening prenatal sonography at 26 weeks. A growth-restricted, microcephalic, and arthrogrypotic infant was delivered alive at 36 weeks but died within an hour despite resuscitation. The neonatal karyotype was normal. Flavivirus IgM antibodies were identified in the serum of the puerpera, once she disclosed that she had traveled from El Salvador to Texas in the early second trimester. Zika virus was identified in the umbilical cord and neonatal brain. Fetal arthritis may precede congenital arthrogryposis in cases of Zika virus infection and may be detectable by prenatal sonography. Physician and health care system vigilance is required to optimally address the significant and enduring Zika virus global health threat.

Reproducible evaluation of tumor-infiltrating lymphocytes (TILs) using the recommendations of International TILs Working Group 2014

Tumor infiltrating lymphocytes (TILs) in breast cancer play an important role in predicting the outcome of breast cancer. The goal of our current study is to investigate the consistency and reproducibility of the recommendations published by the International TILs Working Group 2014 among pathology trainees and pathologists. Hematoxylin & Eosin (H&E) slides from 129 breast cancer cases (one slide each) from 2009 to 2014 were evaluated. Each case was blindly and independently reviewed by two observers following the International TILs Working Group 2014 recommendations. Three pathology trainees (PGY2, PGY3 and PGY4) and three pathologists (2 general pathologists and 1 breast pathologist) were involved in this study. Of the 129 cases, 10 (10/129, 7.8%) cases had TILs >50%, 90 (90/129, 69.8%) cases had <10% of TILs, and 29 (29/129, 22.4%) cases had TILs ranging from 10 to 50%. Our results showed that in 104 cases (104/129, 80.6%) the TILs percentage was identical between the 2 observers. In 18 cases (18/129, 14%), the difference between the two observers was by 10% and in 7 cases (7/129, 5.4%) there was a difference of 20% or more. The inter-observer kappa value was 0.776 between two observers, and the kappa score improved to 0.86 if using the 3 categoric groups (<10%, 10-50%, and >50%). Our study showed that the recommendations and instructions for TILs evaluation by the International TILs Working Group 2014 were sufficiently detailed to be applied for TILs evaluation in breast cancer.

P16-positive cystic squamous cell carcinoma in midline neck: metastasis from oropharynx or primary carcinoma arising from thyroglossal duct cyst?

Cystic squamous cell carcinoma (SCC) of the lateral neck is considered metastatic human papilloma-virus (HPV)-related oropharyngeal SCC (HPV-OPSCC) until proven otherwise. P16 immunohistochemistry is diffusely positive in those carcinomas and is used as a surrogate marker of active human papillomavirus (HPV) infection. Thyroglossal duct cysts (TDC) are one of the differential diagnoses for cystic neck lesions. SCC arising from TDC is extremely rare. In this study, we report a p16-positive cystic SCC located in the midline neck. Radiologic features and the presence of thyroid tissue in the cyst wall indicated that it was a TDC. The morphologic features of the lesion raised the question: is the carcinoma metastatic HPV-OPSCC? The HPV confirmative test, high-risk HPV RNA in situ hybridization, was negative. We then studied p16 immunohistochemistry in the squamous epithelium of benign TDC and found that rare benign TDC can show diffuse and strong p16 positivity.

Tumefactive foreign body giant cell reaction following high pressure paint injection injury: A case report and review of literature

High‐pressure paint injection injury is an uncommon but well‐described injury. The histologic features of long‐term paint injection injury with retained material are less recognized. A 46‐year‐old male presented clinically as “recurrent giant cell tumor of tendon sheath.” The right index finger demonstrated fusiform enlargement by a pigmented mass with diffuse infiltration into the soft tissue of the hand. Histologically the tumor showed multiple giant cells in a fibrotic stroma extending into the dermis. There were multiple types of foreign material including diffuse brown black pigment, weakly optically polarizing foreign material and white inclusions with a “train track” appearance. The cells were positive for CD68 and negative for S100 antigen. Further investigation revealed that the patient had a history of high‐pressure paint injection injury to his digit 6 years prior. Foreign material injected under high pressure into tissues may result in a pseudo‐neoplastic foreign body granulomatous reaction that can mimic giant cell tumor of tendon sheath. Our case demonstrates that this reaction can be florid and can have slow growth over years. A high index of suspicion, a good clinical history and careful examination can distinguish these 2 entities.

Vein of Galen aneurysmal malformations associated with high output cardiac failure: Report of three autopsy cases

Vein of Galen aneurysmal malformations (VGAMs) are rare congenital vascular, malformation. The malformation usually develops between the 6th to 11th wk of gestation. We report three autopsy cases, all prenatally diagnosed by ultrasound or fetal magnetic resonance imaging with VGAM with associated high-output cardiac failure. Prenatal fetal echocardiogram on two patients showed cardiomegaly, ventricular dilatation, pulmonary hypertension and reversed aortic flow. The cause of death in all the three patients was high-output cardiac failure due to VGAM. The autopsy findings confirmed feeding arteries from posterior cerebral arteries to VGAM in all patients. Other significant neuropathologic findings at autopsy were severe hydrocephalus, polymicrogyria, germinal matrix hemorrhage, periventricular leukomalacia, and microcalcification. The findings support that VGAM may be due to abnormal arterial venous communication and the most common cause of death in these patients is high-output cardiac failure. The presence of other associated brain abnormalities indicates a poor prognosis.

Massive, mixed, cystic lesion of the mandibular midline.

CLINICAL PRESENTATIONA 37-year-old white man presented to the emergencyclinic of a teaching hospital complaining of a“swelling” of his chin of 5 months’ duration. While hewas playing with his daughter, she accidently hit hischin, resulting in increasing size, numbness, and painduring eating. The patient had no significant medicalhistory, but he had smoked cigarettes (1 pack per day)since his teenage years. Clinically, the chin mass waslarge (7 6 4 cm), with a slight asymmetry of thesymphysis region. No skin changes, fever, or purulentdischarge were observed.Intraorally, there were multiple carious teeth, themandibular left canine was missing, and the remainingteeth from right second mandibular premolar to left sec-ond premolar exhibited class III mobility; many werehaphazardly displaced. There was slight pain duringpercussionofmostmandibularteeth.Thelesionappearedto be intraosseous, with a considerably expanded cortexthat wasnontender andpliable on both labialand lingualsurfaces.A panoramic radiograph showed a well-circum-scribed radiolucency extending from the right firstmandibular molar to the left first molar, with animpacted left canine displaced to the inferior border.Lateral oblique radiographs helped to further charac-terize the lesion (Figure 1). The lesion had causeddisplacement and considerable external root resorptionof overlying teeth, as well as thinning, expansion, andslight scalloping of the inferior mandibular cortex.There was a thin sclerotic rimming on the left.Conventional computed tomography imaging (softtissue window, with contrast) confirmed the well-circumscribed nature of the lesion and also showedirregularly dense regions of mild opacity, consistentwith soft tissue proliferations, along the lesional pe-riphery and occasionally more centrally (Figure 2);some of these regions had enough density to suggest atleast mild calcification. The bulk of the lesion wasrepresented by a mildly and diffusely gray haze, sug-gesting a fluid content. There were several small, moreradiopaque densities of the posterior portions, and theoverlying cortex was very thin, with occasional perfo-rations not evident on other radiographs. The lesionconsiderably expanded toward the labial, but alsoshowed expansion of the lingual aspect of the mandible.DIFFERENTIAL DIAGNOSISThe massive size of this lesion, with its multiple corticalperforations and associated paresthesia, suggested anaggressive intraosseous neoplasm. However, the well-demarcated borders, cortical expansion, scleroticrimming, and resorbed tooth roots suggested a benignneoplasm or cyst and almost certainly ruled out primarymalignancy or metastatic disease. It was thought thatthe perforations might be explained by palpation traumain such an unusually thinned cortex, or that perhaps the“perforated” areas were merely regions where the cor-tex was so thin that it could not be detected bycomputed tomography technology.The paresthesia would be more difficult to accept fora benign entity if the paresthesia were not bilateral,suggesting a common pressure or ischemic phenome-non from tumor expansion.Three additional and significant features of the lesionprovided important clues to its identity: (1) it was not asolely pericoronal lesion, despite its association with animpacted tooth; (2) it was slightly multilocular, as sug-gested by scalloping of the inferior border; and (3)although basically a cystic radiolucency, it containedscattered radiopacities. The fact that it extended beyondthe cementoenamel junction (see Figure 1, C) broadenedour differential diagnosis and ruled out at least oneexpansile radiolucency, the dentigerous cyst. Addition-ally, the multilocular appearance suggested a number ofclassical lesions, such as ameloblastoma, odontogenickeratocyst (keratocystic odontogenic tumor), glandularodontogenic cyst, odontogenic myxoma, ameloblasticfibroma, central giant cell granuloma, aneurysmal bonecyst, intraosseous mucoepidermoid carcinoma, and cen-tral hemangioma.