21 June 2021: Textbook Updates

We have posted updates of the followingtopics:

Breast > Other benign tumors > Fibromatosis
by Carissa LaBoy, M.D., Kalliopi P. Siziopikou, M.D., Ph.D.
Topic summary: Low grade infiltrative spindle cell neoplasm composed of fibroblasts and myofibroblasts. Bland spindle cells arranged in long intersecting fascicles within a collagenous stroma. May be primary to the breast or be secondary extension into the breast from the chest wall. Up to 95% harbor CTNNB1 activating mutation (sporadic); APC gene inactivating mutation responsible for remainder of cases (hereditary). Can consequently occur after surgery, trauma or rarely, after breast implants. Locally aggressive, local recurrence rates reported in 29% to as high as 40 – 50% of cases after excision. Other treatment options include active surveillance for asymptomatic patients and systemic therapy, such as adjuvant radiation for patients with multiple recurrences.

CNS tumor > Neuronal and mixed neuronal-glial tumors > Diffuse leptomeningeal glioneuronal tumor
by Irfan Yasin, M.B.B.S., Katherine Schwetye, M.D., Ph.D.
Topic summary: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is an indolent, low grade neuroepithelial neoplasm that typically shows widespread leptomeningeal and superficial parenchymal CNS dissemination and oligodendroglioma-like cytology. Typically affects children; rare in adults. Presents with signs and symptoms of obstructive hydrocephalus. Widespread, diffuse involvement of spinal and intracranial leptomeninges. Precise etiology unknown, although recurrent genetic alterations are identified. Often acute, presents with signs and symptoms of increased intracranial pressure. Diagnosis primarily made on radiologic features. Mostly favorable prognosis in terms of mortality. Treatment: surgical resection, particularly for parenchymal lesions.

Kidney nontumor > Glomerular disease > Inherited glomerular disease > Congenital nephrotic syndrome
by Chunlai Zuo, M.D., M.S., Jonathan E. Zuckerman, M.D., Ph.D.
Topic summary: Congenital nephrotic syndrome (CNS) is caused by nephrin (NPHS1) mutations. Affects 1 – 3 per 100,000 live births worldwide. Nephrin is a transmembrane protein of the podocyte foot processes and is a main structural protein of the glomerular slit diaphragm. Heavy proteinuria, hypoproteinemia and edema starting soon after birth. Massive fluid retention and generalized swelling, hypertension and signs of malnutrition and failure to thrive. Typically develop end stage renal disease between ages 2 and 8. Supportive therapy: albumin infusion, gamma globulin replacement, high protein low salt diet, vitamin and thyroxine substitution and infections and thrombotic complications prevention.

Ovary > Serous tumors > Serous cystadenoma / adenofibroma
by Catherine J. Roe, M.D., Krisztina Hanley, M.D.
Topic summary: Benign partially or completely cystic lesion measuring > 1 cm in size and composed of cells resembling fallopian tube epithelium or cuboidal nonciliated epithelium resembling ovarian surface epithelium. Patients present over a broad age range. DNA copy number changes may be seen in stromal fibromatous cells and epithelial cells. Generally asymptomatic. Symptoms related to an ovarian mass; one of the more common ovarian tumors to undergo torsion. Diagnosis through cystectomy or oophorectomy. May recur after incomplete excision. Treatment: surgery (cystectomy or oophorectomy).

Stains & CD markers > Special AT-rich sequence-binding protein 2 (SATB2)
by Simona De Michele, M.D., Helen E. Remotti, M.D.
Topic summary: First identified in 2002 and characterized as a gene involved in cleft palate defects. Nuclear marker normally expressed by epithelium of the lower gastrointestinal tract, brain, nongerminal center lymphoid cells, ductal epithelium of the testis and epididymis. Critical role in neocortical and craniofacial development. Alterations of SATB2 gene (including intragenic duplication, deletions and point mutations in 2q32-q33) have been associated with SATB2 associated syndrome (SAS). Higher SATB2 expression is associated with better prognosis and response to chemotherapy in metastatic colorectal carcinomas.

17 June 2021: Textbook Updates

We have posted updates of the followingtopics:

Appendix > Other tumors > Well differentiated neuroendocrine tumor
by Chien-Kuang Cornelia Ding, M.D., Ph.D., Kwun Wah Wen, M.D., Ph.D.
Topic summary: Well differentiated appendiceal epithelial neoplasms that likely arise from neuroendocrine cells, including enterochromaffin (EC) cell neuroendocrine tumors (NETs), L cell NETs and tubular NETs. Most commonly seen at the tip of the appendix (67% of adult patients, 73% of pediatric patients). Incidence of 0.15 – 0.6 cases per 100,000 person years; slight female predominance and highest incidence before the age of 40 years. Predominantly diagnosed incidentally with other diseases, such as acute appendicitis. Size of the primary tumor is the most reliable indicator of distant metastases (30% in tumors ≥ 2 cm). Simple appendectomy is considered curative for tumor < 1 cm.

Liver & intrahepatic bile ducts > General > Cirrhosis
by Anthony W.H. Chan, M.B.Ch.B.
Topic summary: Diffuse nodulation of liver due to fibrous bands subdividing liver into regenerative nodules. Viral hepatitis B / C, alcoholic liver disease, nonalcoholic (metabolic associated) fatty liver disease are most common causes. Major cause of global health burden, accounting for 1.2% of disability adjusted life years (DALYs) and 2% of deaths worldwide in 2010. General (nonspecific) clinical features: malaise, fatigue, anorexia, weight loss. Diagnosis: ultrasound, CT or MRI radiologically. There are multiple nodular isodense lesions deforming the liver margin on the arterial phase CT. Treatment: treating the underlying cause of cirrhosis, treating and preventing complications, avoiding additional liver injury (e.g. alcohol); patients with MELD ≥ 15 or decompensation should be referred to a transplant center.

Oral cavity & oropharynx > Congenital anomalies > Lingual tonsil
by Molly Housley Smith, D.M.D.
Topic summary: Collection of reactive submucosal lymphoid nodules situated on the dorsal or lateral aspects of the tongue base, which presents clinically as red papules or nodules. Often clinically diagnostic, although asymmetric, hyperplastic nodules may warrant biopsy to rule out lymphoma or other pathology. Associated with obesity, obstructive sleep apnea, laryngopharyngeal reflux, younger age, allergic rhinitis and smoking. Diagnosis is made upon clinical features or awake endoscopy. Head and neck computed tomography (CT), magnetic resonance imaging (MRI) and skull lateral radiographs demonstrate lingual tonsils at the level of the epiglottis on the tongue base. Nonsurgical medical management or surgical debulking / removal may be indicated in cases of hyperplastic lingual tonsil contributing to sleep apnea.

Ovary > Other nonneoplastic > Corpus luteum cyst
by Aurelia Busca, M.D., Ph.D., Carlos Parra-Herran, M.D.
Topic summary: Ovarian cyst > 3 cm in diameter, lined by luteinized granulosa and theca cells. Functional cysts in women of reproductive age, including pregnancy. Corpus luteum is a physiological postovulatory structure formed after the dominant follicle releases the ovum; cystic dilation happens when corpus luteum fails to regress and becomes enlarged with fluid / blood. Patients can be asymptomatic or present with menstrual irregularities, amenorrhea, abdominal pain, palpable abdominal mass if large size. On pelvic ultrasound, appears as simple ovarian cyst, often hemorrhagic; incidental finding or diagnosed during symptomatic workup. Most cysts resolve spontaneously. Resection if symptomatic, rupture or suspicion for neoplastic process.

Stains & CD markers > WT1
by Urooba Nadeem, M.D., Aliya N. Husain, M.D.
Topic summary: WT1 gene encodes for Wilms tumor protein located on chromosome 11p13. Interpretation is based on staining pattern and antibody used. Transcription factor essential for normal development of the urogenital system. WT1 mutations in Denys-Drash syndrome, diffuse mesangial sclerosis kidney, Fraiser syndrome, Wilms tumor in 15% of cases, congenital nephrotic syndrome, cytogenetically normal acute myeloid leukemia and prostate cancer. Can be exclusively nuclear or cytoplasmic according to the antibodies used (anti-C or N terminus WT1 antibody).

14 June 2021: Textbook Updates

We have posted updates of the following topics:

Liver & intrahepatic bile ducts > Benign / nonneoplastic > Hepatocellular adenoma
by Monica Abdelmalak, M.D., Avani Pendse, M.D., Ph.D.
Topic summary: Benign neoplasm of hepatocellular origin arising in the noncirrhotic liver. Female > male, strong association with oral contraceptive exposure. May be asymptomatic and incidentally diagnosed due to imaging performed for an unrelated indication. Unpaired arteries are characteristic; interlobular bile ducts are absent. Liver function tests tend to be normal. Risk of malignant transformation is higher in: men; beta catenin mutated hepatocellular adenoma (HA-B); larger tumors. Treatment for male patients: surgical excision irrespective of size. Treatment for female patients: surgical excision if > 5 cm in size and with beta catenin activating mutations.

Placenta > Gestational trophoblastic disease > Nonneoplastic lesions > Exaggerated placental site
by Absia Jabbar, M.D., Sonali Lanjewar, M.B.B.S., Raavi Gupta, M.D.
Topic summary: Exaggeration of normal physiologic process, with infiltration of the endometrium and superficial third of myometrium by implantation site intermediate trophoblast. Can occur in normal pregnancy or following an abortion; causes postpartum bleeding, uterine atony. Incidence is 1.6% of first trimester spontaneous and elective abortions. Diagnosis: histologic examination. May present as echogenic lesion in the uterine cavity. Excellent prognosis following curettage. Curettage is curative; no follow up is required.

Soft tissue > Fibroblastic / myofibroblastic > Inflammatory myofibroblastic tumor
by Carina Dehner, M.D., Ph.D., Louis P. Dehner, M.D.
Topic summary: Inflammatory myofibroblastic tumor (IMT) is histologically distinctive myofibroblastic spindle cell neoplasm of borderline malignancy, classically featuring an intermixture of plasma cells and lymphocytes. Wide age range but most common in children and young adults. Most common extrapulmonary sites are the mesentery and omentum. Diagnosis: tissue sampling and histological examination. Nonspecific radiology findings; ultrasound may show hypoechoic or hyperechoic mass(es) with ill or well defined borders; increased vascularity on Doppler studies. Generally good prognosis but up to 35% may recur and rare cases of distant metastasis have been reported. Treatment: surgical resection (re-excision of recurrences); specific tyrosine kinase inhibitors, such as crizotinib.

Thyroid & parathyroid > Other thyroid malignancies > Langerhans cell histiocytosis
by Jijgee Munkhdelger, M.D., Ph.D., Andrey Bychkov, M.D., Ph.D.
Topic summary: Langerhans cell hystiocytosis (LCH) is a clonal neoplastic proliferation of langerin / CD1a / S100 positive dendritic cells (Langerhans-like cells). Rare histiocytic neoplasm with occasional involvement of thyroid, either a part of systemic dissemination or isolated. Isolated thyroid involvement is extremely rare. Thyroid involvement can be diffuse (59%) or nodular (25.8%) enlargement. Laboratory: 41% euthyroid, 20% hypothyroid. Diagnosis: fine needle aspiration cytology aided by immunostaining. Excellent prognosis in rare cases with isolated thyroid disease. Treatment: surgical excision for isolated disease, combination chemotherapy for systemic disease.

Transfusion medicine > Transfusion therapy > Irradiation
by Mamie Thant, M.D., Jansen N. Seheult, M.B.B.Ch., B.A.O., M.Sc., M.S., M.D.
Topic summary: Irradiation of cellular blood components is required for certain transfusion recipients to prevent transfusion associated graft versus host disease (TA-GVHD), a rare but usually fatal transfusion related complication with an estimated mortality rate that exceeds 80%. Due to the high mortality rate and limited viable treatment options, risk mitigation strategies for prevention of TA-GVHD are required; irradiation of cellular blood components is currently the cornerstone of prevention of TA-GVHD. Diagnosis of TA-GVHD is based primarily on characteristic clinical findings, although laboratory studies and tissue or bone marrow biopsy may be useful. Treatment for TA-GVHD is largely palliative; prevention is essential.

10 June 2021: Textbook Updates

We have posted updates of the following topics:

CNS tumor > Sellar region tumors > Papillary craniopharyngioma
by Angela France, D.O., Nelli S. Lakis, M.D., M.Sc.
Topic summary: Suprasellar (usually) epithelial encapsulated neoplasm with well differentiated nonkeratinizing squamous epithelium and papillary fibrovascular stroma; BRAF V600E mutation in almost all cases. Incidence: 10% of all craniopharyngiomas; almost always occurs in adults. Lesions usually solid; if cystic, may have mural nodule. Full pituitary endocrine workup is usually mandatory. Prognosis slightly better than adamantinomatous variant. Gross total resection is optimal; smoother surface than adamantinomatous tumors, which facilitates excision.

Coagulation > Acquired bleeding disorders > Disseminated intravascular coagulation (DIC)
by Dong Chen, M.D., Ph.D.
Topic summary: Disseminated intravascular coagulation (DIC) is a systemic activation of the coagulation system, which results in microvascular thrombosis and simultaneously, potentially life threatening hemorrhage attributed to consumption of platelets and coagulation factors. Without adequate treatment, DIC can eventually lead to multiorgan dysfunction / failure. Devastating condition with a poor prognosis; the clinical course is primarily determined by the age of the patient, presence of comorbidities, identification and treatment of underlying etiologies, initial treatment response and severity of organ dysfunction, including the degree of hemostatic abnormalities. Treatment: treat underlying disease; keep fibrinogen levels above 100 mg/dL with cryoprecipitate or fresh frozen plasma.

Nasal cavity, paranasal sinuses, nasopharynx > Sinonasal carcinoma > Sinonasal undifferentiated carcinoma
by Abeer Salama, M.D., Bin Xu, M.D., Ph.D.
Topic summary: WHO definition of sinonasal undifferentiated carcinoma (SNUC): undifferentiated carcinoma lacking evidence of differentiation (such as squamous, glandular or neuroendocrine differentiation) by histology and immunohistochemistry. Diagnosis of exclusion: displays epithelial differentiation but lacks specific squamous, glandular, neuroectodermal, mesenchymal, melanocytic or other lines of differentiation. Rare; 3 – 5% of all sinonasal carcinomas. Presenting symptoms are variable, including nasal obstruction, epistaxis, facial pain and headache to severe visual symptoms and cranial nerve palsies. Overall, 5 and 10 year relative survival rates for SNUC patients were 34.9% and 31.3%, respectively. Multimodal therapy regimens incorporating intensified radiotherapy or chemotherapy after surgery.

Placenta > Gestational trophoblastic disease > Neoplasms > Choriocarcinoma
by Lawrence Hsu Lin, M.D., Ph.D., Deborah DeLair, M.D.
Topic summary: Aggressive form of gestational trophoblastic neoplasia composed of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast. Arises from trophoblastic cells of previous pregnancy, most commonly after complete hydatidiform mole. Vaginal bleeding is the most common symptom. Markedly elevated hCG is a reliable marker of the disease. WHO prognostic scoring system includes age, antecedent pregnancy, interval between diagnosis and index pregnancy, hCG levels, largest tumor size, location and number of metastasis, chemoresistance. Treatment: chemotherapy; surgery only performed in selected cases (older age, chemoresistance, uterine rupture by tumor, life threatening hemorrhage).

Small intestine & ampulla > Congenital anomalies > Heterotopic gastric mucosa
by Aastha Chauhan, M.D., Khalid Amin, M.D.
Topic summary: Heterotopic gastric mucosa:developmental anomaly characterized by ectopic gastric mucosa outside the stomach. Incidence in the duodenum varies from 0.5 to 8.9%. Error in the differentiation of pluripotent primitive endoderm stem cells could lead to the gastric mucosa being present anywhere throughout the gastrointestinal tract. These heterotopic lesions cannot be accurately diagnosed by imaging or endoscopic visualization due to lack of specific features, rendering histopathologic examination as the gold standard for precise diagnosis. Extensive heterotopia increases risk of adverse outcome, including massive hemorrhage or rarely death. Surgery is the treatment of choice, whether it is carried out by laparoscopy or laparotomy.

7 June 2021: Textbook Updates

We have posted updates of the following topics:

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > General > Transient abnormal myelopoiesis associated with Down syndrome
by Tayler A. van den Akker, M.D., Julia T. Geyer, M.D.
Topic summary: Transient abnormal myelopoiesis (TAM) associated with Down syndrome: transient disorder of newborns with Down syndrome or phenotypically normal neonates with trisomy 21 mosaicism. Occurs in 10% of newborns with Down syndrome or trisomy 21 mosaicism. Most patients are asymptomatic but may present with myeloblast organ infiltration. No universal diagnostic criteria. Majority resolve spontaneously over several weeks to 3 months. Treatment is often supportive due to spontaneous remission; in severe organ dysfunction, exchange transfusion, leukapheresis or chemotherapy may be necessary.

Muscle & peripheral nerve nontumor > Inflammatory myopathies > Antisynthetase syndrome associated myositis
by Chunyu “Hunter” Cai, M.D., Ph.D.
Topic summary: Defined by the presence of 1 of the antisynthetase syndrome autoantibodies and at least 1 of the following 3 clinical features: interstitial lung disease, inflammatory myopathy or inflammatory polyarthritis. ~25% of all immune and inflammatory myopathies patients may have antisynthetase syndrome, providing a prevalence estimate of 1/25,000 – 33,000 worldwide. Diagnosis based on clinical features and confirmed in the presence of positive serologic testing for anti-aminoacyl tRNA synthetase antibodies (anti-Jo1, anti-PL12, anti-PL7, anti-OJ, anti-KS, anti-Ha, anti-Zo). Most frequent patterns are nonspecific interstitial pneumonia (70% of the patients) and organizing pneumonia (20% of the patients). Chronic, requiring long term treatment. No FDA approved medication for antisynthetase syndrome.

Prostate gland & seminal vesicles > Acinar / ductal adenocarcinoma > Sarcomatoid carcinoma
by Sami Talibi, M.D., Steven Christopher Smith, M.D., Ph.D.
Topic summary: WHO recognized variant subtype of prostatic adenocarcinoma. Malignant sarcomatoid neoplasm, usually admixed with recognizable prostatic adenocarcinoma but rarely monophasic. Rare, < 200 cases reported; age range: 49 – 88 years. Arises via dedifferentiation from precursor conventional prostatic adenocarcinoma. Diagnosis: biopsy, transurethral resection or prostatectomy specimens. PSA elevated in some cases. Risk factors related to precursor conventional prostatic adenocarcinoma. Organ confined disease has best prognosis. Median overall survival < 1 year. Standard treatments not established.

Ovary > Clear cell neoplasms > Clear cell carcinoma
by Gulisa Turashvili, M.D., Ph.D.
Topic summary: Malignant epithelial tumor composed of clear, eosinophilic or hobnail cells with tubulocystic, papillary and solid growth patterns. May be associated with endometriosis or Lynch syndrome. Accounts for 10 – 12% of ovarian carcinomas in North America. Symptoms related to endometriosis or pelvic mass. Large unilocular, mainly cystic, smooth marginated mass with 1 or more solid nodular protrusions into the cavity on all imaging modalities. Stage is the most important prognostic factor. Treatment: hysterectomy, bilateral salpingo-oophorectomy, omentectomy and staging biopsies.

Stains & molecular markers > PRAME
by Cecilia Lezcano, M.D., Achim A. Jungbluth, M.D., Ph.D., Klaus J. Busam, M.D.
Topic summary: PRAME: preferentially expressed antigen in melanoma. Diffusely positive in most melanomas. PRAME is a cancer testis antigen that was first identified by autologous T cell epitope cloning in a patient with metastatic cutaneous melanoma. Supports a suspected diagnosis of melanoma (usually diffusely positive for PRAME) or nevus (usually negative or only focally positive for PRAME) in conjunction with morphologic evaluation on H&E. PRAME mRNA expression level has been identified as a biomarker for metastatic risk stratification of uveal melanomas and is part of a 12 gene expression prognostic assay.

03 June 2021: Textbook Updates

We have posted updates of the following topics:

Chemistry, toxicology & urinalysis > Management > Assay interferences
by Felix Leung, Ph.D.
Topic summary: Interference is defined as a cause of clinically significant difference in the assay result, due to another component or property of the sample. HIL (hemolysis, icterus, lipemia) interference can be detected on most automated analyzers; other types of interference are often missed and require awareness by both laboratorians and clinicians. Interferents can originate from both exogenous and endogenous sources. Broad categories include chemical, spectral, physical, enzymatic, nonselectivity and additive interference. HIL interferences should be thoroughly assessed and validated prior to implementation of an assay using manufacturer provided information and CLSI guidelines (C56-A and EP07) as reference.

CNS tumor > Sellar region tumors > Pituitary hyperplasia
by Ethar Al-Husseinawi, M.B.Ch.B., Ph.D., Nelli S. Lakis M.D., M.Sc.
Topic summary: Nonneoplastic absolute increase in the number of 1 or more adenohypophyseal cell subtypes seen radiologically as enlargement of the pituitary gland. Nodular or diffuse hyperplasia of polymorphic acini with intact reticulin, without effacement of gland architecture. Very rare, accounting for < 1% of sellar surgical specimens. Mass effect: visual disturbance, bitemporal hemianopia, diplopia, headaches. Diagnosis: history and physical; increase or decrease in corresponding serum hormone levels. Symmetric 2 – 3x enlargement of pituitary gland on CT / MRI. Prognosis excellent with medical treatment. Usually correct underlying endocrinologic disturbance; surgery rarely indicated.

Colon > Inflammatory bowel disease > Ulcerative colitis
by Rachel Horton, D.O., Catherine E. Hagen, M.D.
Topic summary: Idiopathic chronic inflammatory disorder of the colon mucosa. Begins in the rectum and continues proximally in a continuous pattern to include up to the entire colon (pancolitis). Higher incidence (9 – 20/100,000 person years) and prevalence (156 – 291/100,000 people) in populations of North American and Northern European descent. Pathophysiology not fully known but appears to be a complex multifactorial process involving an overwhelming T helper type 2-like immune response, leading to mucosal injury in response to gut microbial dysbiosis in genetically predisposed patients. Diagnosis: correlation of clinical symptoms with endoscopic and histological examination. Treatment: 5-aminosalicylate agents are first line therapy for mild to moderate disease.

Liver & intrahepatic bile ducts > General > Histology
by Nicole Leonard, M.D., Kimberley J. Evason, M.D., Ph.D.
Topic summary: Liver is the largest solid organ and is located in the right upper quadrant of the abdomen. Functional unit is the hepatic lobule, composed of hepatocyte plates surrounding a central vein with portal tracts at the periphery. Metabolic differences among the zones of hepatic lobules influence hepatocytes’ susceptibility to viral infection, drug injury, nonalcoholic fatty liver disease and other insults. Laboratory: aspartate transaminase (AST) and alanine transaminase (ALT) to evaluate potential hepatocyte damage. Kupffer cells, endothelial cells, hepatic stellate cells, sinusoids, bile canaliculi, the space of Disse and intracellular components like mitochondria may be visualized with electron microscopy.

Ovary > Germ cell tumors > Yolk sac tumor
by Gulisa Turashvili, M.D., Ph.D.
Topic summary: Primitive germ cell tumor with a variety of morphologic patterns, ranging from endodermal extraembryonic structures (secondary yolk sac, allantois) to, less commonly, endodermal somatic tissues (intestine, liver, mesenchyme). Most common before the age of 30. ~20% of malignant germ cell tumors of the ovary. Chromosome 12 abnormalities, usually isochromosome 12p, in ~75% of patients. Diagnosis: microscopic examination. Usually favorable prognosis due to chemosensitivity, with complete cure in > 80% of cases. Treatment: unilateral salpingo-oophorectomy.

27 May 2021: Textbook Updates

We have posted updates of the following topics:

Breast > Inflammatory > Silicone leak / lymphadenopathy
by Maria A. Arafah, M.D., Afaf M. Alsharhan, M.D.
Topic summary: Foreign body inflammatory reaction induced by leakage of silicone gel contained in prostheses. Most common sites: breast, regional lymph nodes. Firm to hard nodular surface, gritty if there is calcification. Incidence rates vary between manufactures and radiological detection methods. Breast implant rupture is often clinically silent. Histopathology is the gold standard for a definitive diagnosis. Treatment: replacement of the prosthesis with removal of the surrounding contracture; excision of enlarged masses or lymph nodes caused by migration of silicone.

Liver & intrahepatic bile ducts > Noninfectious hepatitis > Autoimmune hepatitis
by Anthony W.H. Chan, M.B.Ch.B.
Topic summary: Immune mediated inflammatory liver disease of uncertain cause. Diagnosis is based on combination of clinical, laboratory and histological features; more common in female patients. Incidence is highest in North America (42.9/100,000), followed by Europe (10.7 – 23.9/100,000). Etiology unknown; genetic and environmental factors may play roles in pathogenesis. Most patients have nonspecific symptoms: fatigue (85%), anorexia, nausea, weight loss, jaundice, pruritus, amenorrhea. Good prognostic factor: IgG4 associated autoimmune hepatitis. Treatment: corticosteroids alone or with azathioprine to achieve normalization of serum transaminases and IgG.

Skin nontumor > Alopecia > Alopecia areata
by Jasmine Saleh, M.D., M.P.H., Jodi Speiser, M.D.
Topic summary: Hair loss secondary to an autoimmune disorder that targets the hair follicle bulb. A characteristic clinical finding is exclamation point hairs: 2 – 3 mm hairs that appear to float on the scalp because of shaft narrowing and hypopigmentation near the scalp surface that appear at the advancing margin of the patches. Affects males and females of all ages and ethnicities. Exact mechanism is not yet understood although a genome wide association study provided evidence that both acquired and innate immunity contribute to the pathogenesis of alopecia areata. Diagnosis: scalp biopsy followed by histologic examination. First line treatment: topical or intralesional corticosteroid, minoxidil, anthralin, topical immunotherapy (i.e. diphenylcyclopropenone, squaric acid dibutylester and dinitrochlorobenzene) or topical retinoids.

Stains & molecular markers > GMS
by Fang Zhou, M.D.
Topic summary: Grocott-Gomori methenamine silver (GMS) is a special stain to detect fungi. Outlines fungal organisms by staining polysaccharides in cell walls. Aldehyde groups form on polysaccharides (1,2-glycols) via oxidation by chromic acid; weaker oxidizers like periodic acid (which is used in PAS and Jones stains) have more staining of background structures. GMS is ordered when fungi are suspected on H&E or cytology preparations. Relatively quick and cost effective; however, sensitivity is low and cannot provide definitive organism identification.

Transfusion medicine > Blood bank testing > Pretransfusion testing
by Deanna C. Fang, M.D., Huy P. Pham, M.D., M.P.H.
Topic summary: Testing performed by the transfusion service before a transfusion; current scope excludes donor testing performed by collection facility. Based on serologic testing methods (molecular testing alone is not sufficient). Computer (electronic) crossmatch – where a computer / software assesses ABO compatibility based on patient and donor ABO typing. Most laboratories use tubes with ethylenediaminetetraacetic acid (EDTA) (pink or lavender top) but tubes with acid citrate dextrose (ACD) (yellow top) or without anticoagulant (red top) are also acceptable if they have been validated by the laboratory.

24 May 2021: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Urothelial neoplasms – noninvasive > Noninvasive papillary urothelial carcinoma high grade
by Yan Hong Shirley Yu, M.D., Michelle R. Downes, M.D.
Topic summary: Noninvasive papillary urothelial carcinoma high grade: neoplastic proliferation of the urothelium with a papillary configuration and no invasion beyond the basement membrane. Complex solid to fused papillary architecture, nuclear atypia, pleomorphism, crowded and overlapping cells, brisk mitotic activity. Most commonly found in posterior and lateral walls of bladder. Etiology: smoking; occupational exposure to chlorinated hydrocarbons, polycyclic aromatic hydrocarbons and aromatic amines; arsenic exposure. Cystoscopy: exophytic lesion, solitary or multiple, with varying size. Treatment: surgical transurethral resection of tumor.

Informatics, digital & computational pathology > Fluorescence microscopy > Fluorescent microscopy applications
by Ruhani Sardana, M.B.B.S., Anil Parwani, M.D., Ph.D., M.B.A.
Topic summary: Noninvasive form of optical imaging which applies the principle of fluorescence in the diagnostic / investigative study of organic and inorganic components of the specimen. Applications: rapid diagnosis of different fungi, such as yeast, Microsporum, Trichophyton, etc., especially in immune compromised patients; determining the location of an antigen or antibody in a tissue section or smear by the pattern of fluorescence; diagnosis of invasive carcinomas, which present as bright masses with irregular borders composed of fluorescent neoplastic nuclei with surrounding hypofluorescent fibroadipose tissue. Suitable for rapid tumor detection due to the possibility of enhancing visibility of nuclei.

Informatics, digital & computational pathology > Laboratory information systems > Data representation and communication standards
by Ngoc Tran, M.D., M.S., Chris Williams, M.D.
Topic summary: Laboratory information is stored and transferred using a variety of formats and standards. Capturing information as structured data, utilizing common code sets when possible, facilitates future research, analysis and collaboration. Health Level Seven (HL7) is the common messaging standard used for intralaboratory and interlaboratory communication, as well as healthcare information exchange at the enterprise level. Coding systems are common examples of structured data in healthcare; Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes (LOINC) are particularly useful for searching data in the Laboratory Information System (LIS), if available.

Transfusion medicine > Transfusion reactions & complications > Transfusion associated circulatory overload
by Tiffany Chambers, M.D., Mrigender Virk, M.D.
Topic summary: Transfusion associated circulatory overload (TACO) is a form of cardiopulmonary edema due to the inability to tolerate the volume or rate of transfusion. Transfusion increases intravascular volume. Symptoms: dyspnea, orthopnea, cough, headache, chest tightness, hypertension, tachycardia, hypoxia, widened pulse pressure, jugular venous distension. Carefully consider the need for transfusion, weighing it against the potential risks of transfusion and avoid unnecessary transfusions by adhering to restrictive thresholds for hemodynamically stable patients. Slowing the rate of transfusion or concurrent diuretic treatment may alleviate future incidents of TACO.

Uterus > Stromal tumors > Low grade endometrial stromal sarcoma
by Elizabeth Kertowidjojo, M.D., Ph.D., M.P.H., Lora Hedrick Ellenson, M.D.
Topic summary: Low grade endometrial stromal sarcoma: malignant mesenchymal tumor comprised of cells resembling proliferative phase endometrial stroma with infiltrative growth or lymphovascular invasion. Histologic features include permeative tongue-like islands of tumor cells composed of monotonous oval to spindle cells with minimal cytologic atypia, often demonstrating whorling around blood vessels; smooth muscle and sex cord-like differentiation are common. Second most common uterine sarcoma. Abnormal uterine bleeding (most common), pelvic pain, uterine mass. Typically indolent, with an overall 5 year survival of > 90% and a 10 year survival of 75%. Treatment: hysterectomy and bilateral salpingo-oophorectomy.

20 May 2021: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Urothelial carcinoma – invasive > Sarcomatoid variant
by Megan L. Brown, M.D., Maria Tretiakova, M.D., Ph.D.
Topic summary: Variant of urothelial carcinoma; morphologically indistinguishable from sarcoma. Biphasic malignant neoplasm with morphologic and immunohistochemical evidence of both epithelial and mesenchymal differentiation. Estimated to represent 0.3 – 0.6% of all urothelial carcinomas. Sites: kidney pelvis, proximal ureter and bladder. Probably has a common malignant clonal origin, with epithelial and mesenchymal differentiation. Poor prognosis, as frequently presents at an advanced stage and is associated with a worse overall survival when compared with pure urothelial carcinoma. Chemotherapy resistant; no standard treatment due to rarity.

Breast > General > Histology
by Indu Agarwal, M.D., Luis Blanco, Jr., M.D.
Topic summary: Mammary glands located on the upper anterior thorax that produce and secrete milk in females. Adult female breast consists of branching ducts and acini; the acini group together to form lobules. Considered an epidermal gland, as it develops as diverticula of epidermis into dermis. Menstrual cycle related changes clinically manifested by changes in breast size and texture, varies between individuals. Dramatic increase in the number of lobules, as well as acinar units during pregnancy / lactation. Menopause: reduction of estrogen and progesterone causes involution and atrophy of TDLUs. Identical in males and females at birth.

Informatics, digital & computational pathology > Whole slide imaging > WSI implementation & primary diagnosis
by Mark D. Zarella, Ph.D.
Topic summary: Whole slide imaging (WSI) is a method for digitizing glass slides in their entirety. Implementation of WSI benefits from oversight by pathologists and laboratorians. Clinical use cases: slides can be scanned post signout to retain digital copies; images can simultaneously be viewed and navigated by different users; scanned slides can be made accessible remotely to enable remote consultation. Archived slides can be associated with the clinical case by integration into the laboratory information system or electronic health record, making them easily accessible for follow up. Primary diagnosis: Can be performed using WSI; requires validation demonstrating concordance with glass slides.

Skin nonmelanocytic tumor > Adnexal tumors > Sweat gland derived (apocrine & eccrine glands) > Hidradenoma
by Jasmine Saleh, M.D., M.P.H., Jodi Speiser, M.D.
Topic summary: Benign dermal nodule of eccrine / apocrine gland derivation. Presents as a slow growing, nodular, solid or cystic cutaneous mass usually measuring up to 3 cm in diameter. Overlying skin can be flesh colored, erythematous or blue and may exhibit superficial ulceration or serous discharge. Frequently occurs in the third to fifth decade of life with a slight predominance in females. Typically located on the head, neck and limbs (although any site may be affected). Treatment: wide local excision; recurrence rate of 12% if not completely excised.

Stains & molecular markers > YAP1
by Y. Albert Yeh, M.D., Ph.D.
Topic summary: YAP1 (yes associated protein 1) is a transcriptional regulator that activates gene transcription involved in cellular survival and proliferation and suppresses apoptotic genes. Pathophysiology: when Hippo signaling pathway is on, mammalian STE20-like protein kinase 1 / 2 (MST1 / 2) and salvador family WW domain containing protein 1 (SAV1) are activated. YAP1 expression is associated with cancer development, including promoting malignant transformation, proliferation of cancer stem cells and drug resistance. Loss of YAP1 C terminus expression for detecting YAP1 fusion in porocarcinoma and poroma. Overexpression of cytoplasmic YAP1 predicted unfavorable prognosis in colorectal cancer.

17 May 2021: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Urothelial carcinoma – invasive > Nested
by Megan L. Brown, M.D., Maria Tretiakova, M.D., Ph.D.
Topic summary: Morphologic variant of urothelial carcinoma characterized by unusually bland, nested pattern of invasion but with clinical outcomes similar to conventional invasive high grade urothelial carcinoma. Nested urothelial carcinoma has been expanded to include: large nested carcinoma. Very rare in renal pelvis and overall rare in genitourinary tract; only a few hundred cases reported. TERT promotor mutations. No specific risk factors to development of nested variant reported. Clinical features: hematuria, dysuria, flank pain. Diagnosis: cystoscopy, CT scan, MRI.

Esophagus > Congenital anomalies > Ectopic sebaceous glands
by Yukihiro Nakanishi M.D., Ph.D.
Topic summary: Heterotopic / ectopic sebaceous glands in the esophagus. Incidentally found, small (3 – 4 mm) yellowish plaques with granular or lobulated appearance; the number of lesions varies from single to more than 100. Reported incidence is low; Reported age range 45 – 79 years. Sites: middle and lower esophagus. Whether heterotopic / ectopic sebaceous glands in the esophagus are the result of congenital anomaly or metaplastic change of squamous epithelium remains unknown. Usually asymptomatic. Diagnosis confirmed via biopsy. No treatment required.

Laboratory Administration & Management of Pathology Practices > Operations > Lean workflow / Six Sigma
by Lewis A. Hassell, M.D., Stephen J. Hardy, M.B.A.
Topic summary: Lean Six Sigma is a customer focused, team oriented and data driven performance improvement and problem solving technique directed at breakthrough improvement to essential business processes. It has a proven record of breakthrough improvements in laboratory and healthcare services, significantly improving quality and safety outcomes. Lean: set of methods intended to drive out waste and improve process flow. Six Sigma: a quality improvement methodology oriented around reduction of defects or errors to less than 3.4 defects per million opportunities. Project team that includes both the emergency department and laboratory staff is more effective when working to improve emergency department laboratory test turnaround time.

Liver & intrahepatic bile ducts > Biliary tract disease > Ductular reaction
by Shahbaz Khan, M.D., Romil Saxena, M.B.B.S.
Topic summary: Complex, dynamic and nonspecific reaction to liver injury and disease (acute and chronic), characterized by a ductular phenotype, possibly but not necessarily of ductular origin, at the portal – parenchymal interface. Ductular reactions (DRs) are a response to a wide variety of hepatobiliary injuries that aim to restore compromised physiological function after liver injury; variable degree of bile duct profiles, portal edema, fibrosis and an inflammatory infiltrate composed mostly (but not always) of neutrophils. Predominantly associated with biliary diseases but can be seen secondary to any liver injury. Diagnosis: liver biopsy.

Skin nonmelanocytic tumor > Other tumors of skin > Juvenile xanthogranuloma
by Lamiaa Hamie, M.D., M.Sc., Ossama Abbas, M.D.
Topic summary: Rare, benign disorder which results from the proliferation of factor XIIIa positive dendritic cells; most common form of non-Langerhans cell histiocytosis. Occurs predominantly in young children; between 40 – 70% of cases arise in the first year of life. Presents as a solitary cutaneous nodule on the head, neck or trunk. Etiology unknown. Diagnosis is made clinically based on the typical appearance of lesions on physical examination in most cases. Has a good prognosis; lesions usually regress spontaneously. No treatment is usually required; excision can be done for cosmetic concerns.