8 June 2023: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Glandular neoplasms > Urachal adenocarcinoma
by Rugvedita Parakh, M.D., Maria Tretiakova, M.D., Ph.D.
Topic summary: Adenocarcinoma arising from the epithelium lined tubular structure known as urachus, an embryological derivative of the urogenital sinus and allantois that connects the bladder to the umbilicus; diagnosis of urachal adenocarcinoma is usually established after excluding other mimics. Rare, < 1 case per 1 million of population. Clinical features: hematuria and irritative bladder symptoms with voiding difficulties (hematuria, dysuria, nocturia, frequency, suprapubic pain). Urachal adenocarcinoma is a clinicopathologic diagnosis. Staging is different than bladder carcinoma; local recurrence and metastatic disease are common. Treatment: umbilectomy with partial cystectomy, possibly laparoscopic.

Cervix > Inflammatory / infectious > Lactobacillus
by Hiba Al Dallal, M.B.Ch.B., Ziyan T. Salih, M.D.
Topic summary: Lactobacillus spp. is normal vaginal flora that is commonly seen in cervical Pap smears; they are beneficial because they produce lactic acid, which reduces the vaginal pH and possibly protects from infection by Candida and other pathogens. Lactobacillus is predominant during the second half of the menstrual period (luteal phase). They are blue thick rods usually found on the top of the intermediate squamous cells.They can lyse glycogen rich intermediate cells which may cause cytolysis. Excessive lactobacterial cytolysis can be associated with vaginosis-like symptoms (cytolytic vaginosis) and may cause vulvovaginal itching, burning and discharge. No treatment is needed.

CNS & pituitary tumors > Gliomas, glioneuronal tumors, and neuronal tumors > Neuronal and mixed neuronal-glial tumors > Central neurocytoma
by Daniel D. Child, M.D., Ph.D., Rebecca Yoda, M.D.
Topic summary: Rare, well differentiated, intraventricular neoplasm with neuroepithelial differentiation, typically arising near the foramen of Monro. Microscopically appears as sheets of uniform, small – medium, round cells with fine chromatin stippling (salt and pepper) and occasional perinuclear clearing, interspersed with patches of fibrillary matrix. ~0.1 – 0.5% of all primary brain tumors; mean age at presentation: 20 – 34 years. Most common presenting symptoms are related to increased intracranial pressure that is due to obstructive hydrocephalus. Generally favorable prognosis: 5 year overall survival rate: 96%; 10 year overall survival rate: 82%. Surgical resection is standard of care; when complete resection is not possible, adjuvant radiotherapy improves survival.

Informatics, digital & computational pathology > Laboratory information systems > LIS fundamentals
by Ugochukwu John Jonah, M.B.B.S., Anil Parwani, M.D., Ph.D., M.B.A.
Topic summary: A laboratory information system (LIS) is computer software that processes, stores and manages data from all stages of medical processes and tests: patient check in, order entry, specimen processing, results entry and patient demographics. It reduces the turnaround time of laboratory tests and significantly decreases errors. LIS is only certified to be of functional capacity when it meets the meaningful use program criteria of the 2009 Health Information Technology for Economic and Clinical Health (HITECH) Act; such certified LIS is usually referred to as an electronic health record [EHR] module. Ideal LIS will prevent unauthorized access in order to preserve the confidentiality of health records and ensure that only legitimate users can be granted access to the system.

Oral cavity & oropharynx > Benign epithelial tumors & processes > Verruca vulgaris
by Molly Housley Smith, D.M.D.
Topic summary: Benign epithelial proliferation of squamous mucosa; associated with human papilloma virus (HPV) types 2 and 4. Mostly found on the skin but uncommonly may be seen in the oral cavity; similar to cutaneous lesions both histopathologically and microscopically. M > F; wide age range, although more frequent in younger populations. Asymptomatic, well delineated, often white papule or nodule with a papillary or pebbled surface. Lips, palate, anterior tongue most common but can affect any intraoral location. HPV is thought to gain access to epithelial cells via microabrasion or trauma. Treatment: excision (via surgery, cryosurgery or electrosurgery); spontaneous regression has been reported. Good prognosis; rare recurrence attributed to incomplete removal of lesional tissue.

5 June 2023: Textbook Updates

We have posted updates of the following topics:

CNS & pituitary tumors > General > WHO classification
by Maria Martinez-Lage, M.D.
Topic summary: 2021 WHO classification, 5th edition (WHO CNS5) builds upon the updated fourth edition published in 2016 and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW). This fifth edition incorporates major changes including further advancing the role of molecular information in the diagnosis of CNS neoplasms, introducing the concept of CNS WHO grade distinct from WHO grade, grading within tumor type, endorsing the use of Arabic numerals for grading instead of Roman numerals and defining new entities based on molecular and histological characteristics. In addition to NOS (not otherwise specified), NEC (not elsewhere classified) is introduced.

Informatics, digital & computational pathology > Digital and whole slide imaging > WSI commercial platforms
by Nat Pernick, M.D.
Topic summary: Whole slide imaging has become increasingly adopted by pathologists as a tool to digitalize pathology. Here major manufacturers of whole slide scanners and 2 of each of their representative products are listed as a resource for the pathology community. Manufacturers listed here include 3DHISTECH, Akoya Biosciences, Bionovation Biotech, Grundium, Hamamatsu Photonics, Huron Digital Pathology, KFBIO Digital Pathology, Leica Biosystems, Mikroscan Technologies, Motic Digital Pathology, Nikon, Objective Imaging, OptraSCAN, Philips Healthcare, Pramana, PreciPoint, Roche Diagnostics, Scopio Labs, Visiopharm.

Small intestine & ampulla > Infectious disorders > Giardia lamblia
by Iresha Vithanage, M.B.B.S., M.D., Saroona Haroon, M.B.B.S.
Topic summary: Protozoan disease caused by Giardia lamblia / Giardia intestinalis, a common parasite that can be detected in small bowel biopsies; it can also be detected in stool. Asymptomatic colonization or acute or chronic diarrheal illness; can be histologically confirmed by visualization of the organisms. Common in areas with poor sanitation and limited water treatment facilities. Giardia intestinalis infection causes enterocyte damage and loss of brush border of the epithelial cells of the small intestine, which leads to shortening of microvilli and altered epithelial barrier function. Overall prognosis is good with treatment; dehydration can be life threatening for infants and pregnant women. Commonly treated by antibiotics such as metronidazole, tinidazole and nitazoxanide.

Soft tissue > Vascular > Benign > Lymphangioma
by Farres Obeidin, M.D.
Topic summary: Benign localized or diffuse vascular proliferation composed of lymphatic vessels. May be either microcystic or macrocystic in nature. Wide age range but predominant in children and young adults. Many lymphatic malformations show somatic mutations in PIK3CA. Clinical history and imaging studies can suggest a lymphangioma; usually diagnosed on simple excision or incidentally on biopsy. Benign with a generally excellent prognosis in adults; locally recurrent potential (~20% of tumors): younger age and presence of associated symptoms of infection, dyspnea, dysphagia or hemorrhage are associated with higher rates of recurrence. Treatment depends heavily on the clinical presentation, size and location; small or localized lesions are generally amenable to surgical resection.

Transfusion medicine > Therapeutic apheresis > Leukocytapheresis
by Brian D. Adkins, M.D., Garrett S. Booth, M.D., M.S.
Topic summary: Leukocytapheresis is the removal of white blood cells via apheresis. Therapeutic leukocytapheresis is performed to acutely lower a patient’s white blood cell (WBC) count due to symptoms associated with hyperleukocytosis or increased viscosity. Usually associated with acute myeloid leukemia (AML) with WBC > 100,000/μL, lymphoblastic leukemia / lymphoma (ALL) with WBC > 400,000/μL. Patients may present with disseminated intravascular coagulation (DIC), tumor lysis syndrome or hypoxic ischemic type injury. Usually performed emergently using femoral apheresis or a dialysis catheter, which do not require radiographic confirmation. Chemotherapy should be initiated as quickly as possible and should supersede leukocytapheresis if patients are asymptomatic.

1 June 2023: Textbook Updates

We have posted updates of the following topics:

Appendix > Appendicitis > Interval appendicitis
by Pu Ni, M.D., Qingqing Liu, M.D., Ph.D.
Topic summary: Interval appendectomy is usually performed in patients with complicated appendicitis (i.e., rupture) who are clinically stable; these patients are treated with initial antibiotic therapy or drainage followed by a delayed appendectomy. Clinical symptoms caused by acute appendicitis (e.g., abdominal pain, fever, poor appetite, etc.) usually improve after initial nonsurgical management. Interval appendectomy is often performed to exclude an appendiceal neoplasm. Radiological findings after initial nonsurgical management include normal appendix to inflamed appendix, presence of residual abscess or resolution of the abscess. Conservative treatment is effective in a high percentage of patients with acute appendicitis, with success rates ranging from 68% to 95% and a relative low recurrence rate of ~10%.

Cytopathology > Lung > Nondiagnostic
by Mir Yousufuddin Ali Khan, M.D., Vinod Shidham, M.D.
Topic summary: Lung cytopathology involves the assessment of specimens that can be categorized into exfoliative cytology (sputum, bronchial brushing, bronchial wash and bronchoalveolar lavage) and FNA cytology (percutaneous transthoracic and endobronchial ultrasound guided). Nondiagnostic / inadequate / insufficient specimen lacks sufficient material in quantity or quality for a reliable diagnosis. Most common causes are insufficient cellularity, cellular degeneration, poor preservation of cells and hemorrhagic samples. Bronchoalveolar lavage with fewer than 10 alveolar macrophages per 2 mm2 using a high power field diameter of 0.5 mm, is considered inadequate. Risk of malignancy is 40% for a nondiagnostic specimen.

Kidney nontumor / medical renal > Glomerular disease > Focal segmental glomerulosclerosis (FSGS) > Focal segmental glomerulosclerosis-general
by Giorgio Cazzaniga, M.D., Vincenzo L’Imperio, M.D.
Topic summary: Group of podocytopathies with different etiologies presenting with focal and segmental glomerulosclerosis (FSGS) along with nephrotic or subnephrotic proteinuria. Distinction should be made between the nonimmune complex mediated disease (FSGS) and the pattern of injury (segmental and focal sclerosis) due to other underlying glomerular conditions (e.g., immune complexes). Recently proposed clinicopathological classification divided FSGS based on etiology into 3 categories: primary, secondary and genetic. ~30 – 60% of patients will inexorably progress to end stage kidney disease (ESKD) over a 5 – 10 year period of observation. High dose oral glucocorticoids is the first line immunosuppressive treatment for primary FSGS.

Prostate gland & seminal vesicles > Acinar / ductal adenocarcinomas > Microcystic adenocarcinoma
by Ankur Sangoi, M.D.
Topic summary: One of the unusual histological patterns of acinar adenocarcinoma; while often easier to recognize at radical prostatectomy given the juxtaposition to usual pattern acinar adenocarcinoma (incidence of 11%), deceptive morphology can be challenging to recognize on prostate biopsy (incidence of 1%). Cystic glands with marked dilatation at low power magnification but often showing luminal crystalloid, blue intraluminal mucin and prominent nucleoli at higher power magnification. Diagnosis: core needle biopsies or transurethral resection of the prostate; immunohistochemistry may be used to confirm the absence of basal cells. One of the important deceptively bland histological patterns of prostate cancer, alongside atrophic, pseudohyperplastic and foamy gland prostatic adenocarcinoma.

Soft tissue > General > Staging
by Borislav A. Alexiev, M.D.
Topic summary: Includes soft tissue tumors of intermediate (locally aggressive and rarely metastasizing) potential and malignant soft tissue tumors. Sarcomas arising within the confines of the dura mater, including the brain, are not optimally staged by this system. Locally aggressive soft tissue neoplasms, which may recur locally but have either no risk of metastatic disease or an extremely low risk of metastasis, are excluded from the AJCC soft tissue sarcoma staging system. Reporting of pT (tumor), pN (lymph node) and (when applicable) pM (metastasis) categories is based on information available to the pathologist at the time the report is issued; as per the AJCC, it is the managing physician’s responsibility to establish the final pathologic stage based upon all pertinent information.

30 May 2023: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Other chondrogenic tumors > Enchondroma
by Borislav A. Alexiev, M.D.
Topic summary: Enchondroma is a benign hyaline, cartilaginous tumor that arises within the medullary cavity of bone. Histology with typical encasement pattern (deposition of bone surrounding the tumor lobules, a sign of indolent growth). 20% of all cartilaginous tumors, second only to osteochondroma (30%); most common in 20 – 50 year olds. Increased levels of D-2-hydroxyglutarate (D-2-HG) can be detected in cartilage tumors with an IDH1 or IDH2 mutation. Most common presenting symptoms are pain, swelling and deformity. Asymptomatic enchondromas can be followed clinically and do not need to be treated. Management of symptomatic enchondroma lesions typically involves surgical management in the form of simple curettage with bone grafting.

CNS nontumor > Toxic and metabolic disorders > Radiation injury
by Palgun Nisarga, M.D., Kymberly A. Gyure, M.D.
Topic summary: Radiation therapy is commonly used as adjuvant therapy for malignant CNS neoplasms. Radiation injury mainly affects white matter and includes autonomic, cognitive and functional deficits. Typically classified based on time of appearance of symptoms: acute radiation induced brain injury (days to weeks); early delayed radiation induced brain injury (weeks to 3 – 6 months); late radiation induced brain injury (focal and diffuse, > 3 – 6 months). Unknown predisposing intrinsic factors (location treated, age, clinical status, tumor diagnosis and genetic susceptibility); partly identified extrinsic factors (dose / therapy technique). Oral corticosteroids used for symptomatic cases; resection with frozen section diagnosis; no known medical therapy for cognitive impairment.

CNS & pituitary tumors > Cysts > Arachnoid cyst
by Saman Seyed Ahmadian, M.D.
Topic summary: Arachnoid cysts are nonneoplastic, intracranial cerebrospinal fluid (CSF) filled spaces lined with arachnoid membranes. They are classified as primary developmental or secondary cysts. Primary developmental cysts occur due to the splitting of arachnoid membranes in utero, resulting in abnormal collections of CSF; 50 – 65% present in the middle cranial fossa / Sylvian fissure. Secondary cysts are less common and often occur after trauma, infection or surgery. CT and MRI are used for radiologic assessment; surgical resection is required for a definitive diagnosis. Clinical features depend on size and location: headaches are the most common symptom; arachnoid cysts can also be asymptomatic. Treatment: surgery if symptomatic.

Molecular markers > MYD88
by Yan Chen Wongworawat, M.D., Ph.D., Kevin E. Fisher, M.D., Ph.D.
Topic summary: MYD88 innate immune signal transduction adaptor; MYD88 gene (NM_002468.5) is located on chromosome 3p22.2 and has 5 exons. Somatic activating mutations in MYD88 are the most frequent molecular alteration in patients with lymphoplasmacytic lymphoma (LPL) and Waldenström macroglobulinemia (WM) and are seen in > 90% of cases. Inherited / germline mutations in this gene are associated with immunodeficiency 68 (ID68), an autosomal recessive primary immunodeficiency characterized by severe systemic and invasive bacterial infections beginning in infancy or early childhood. Detection of MYD88 activating mutations requires sequencing based methods such as Sanger sequencing, next generation sequencing or pyrosequencing.

Uterus > Endometrial hyperplasia > Progestin therapy related changes
by Carlos Parra-Herran, M.D.
Topic summary: Hysterectomy is the standard treatment for endometrial intraepithelial neoplasia (atypical hyperplasia) and low grade endometrial endometrioid adenocarcinoma. Hormonal therapy is a valid alternative for premenopausal women who desire to preserve fertility, as well as patients in which surgical treatment is not feasible. 2 main types of fertility sparing treatment are oral progestins and a levonorgestrel releasing intrauterine device. Factors associated with higher likelihood of remission under progestin therapy: young age, previous pregnancy, infertility, index diagnosis of endometrial intraepithelial neoplasia / atypical hyperplasia (versus endometrioid carcinoma) and treatment with megestrol acetate (versus other forms of treatment).

25 May 2023: Textbook Updates

We have posted updates of the following topics:

Anus & perianal area > Carcinoma > Adenocarcinoma
by Raul S. Gonzalez, M.D.
Topic summary: Rare adenocarcinoma that primarily involves the anal canal (not rectal adenocarcinomas with downward spread). May arise from anal glands, from congenital anorectal duplications or along a fistula tract. 5% of anorectal malignancies; slightly more common in white men. Proposed etiologic associations include chronic fistula, anal Crohn’s disease and anal sexual intercourse. Often a long history of perianal fistulas, abscesses, surgery; indolent course with gradual progression. Poor prognosis associated with advanced T and N category disease and higher histologic grade. Standard treatment includes abdominoperineal resection; adding chemotherapy and radiation improves outcome.

Anus & perianal area > Carcinoma > Paget disease
by Raul S. Gonzalez, M.D.
Topic summary: Intraepithelial tumor usually of apocrine or possibly eccrine gland origin. Intraepidermal neoplastic cells, sometimes linked to anal malignancy (secondary) but may also be primary disease. More common in older patients. Typically indolent but often recurs. Up to 40% of patients with anal Paget disease have secondary disease (associated with an underlying malignancy); usually adenocarcinoma but sometimes other forms, such as neuroendocrine carcinoma. Arises anywhere between the dentate line and the perianal skin. May be related to epithelial – mesenchymal transition. Diagnosis: tissue sampling. Treatment: wide local excision or radiotherapy.

Molecular markers > RAS Q61R IHC
by Leila Moayed-Alaei, M.D., Andrew J. Colebatch, M.B.B.S., Ph.D.
Topic summary: NRAS (neuroblastoma RAS viral oncogene homolog) is a proto-oncogene located on chromosome 1p13.2; mutant NRAS was first identified as a transforming gene in a neuroblastoma cell line (SK-N-SH). Strong and diffuse cytoplasmic or membranous staining of RAS Q61R is interpreted as positive staining. Diffuse and strong cytoplasmic or membranous staining is confined to myoepithelial cells in salivary gland neoplasms. Pitfall in IHC: the immunohistochemistry is not specific for NRAS Q61R mutation and will stain HRAS Q61R and KRAS Q61R as well. RAS Q61 immunohistochemistry is used by pathologists to identify mutation in codon 61 of HRAS, KRAS and NRAS gene.

Skin melanocytic tumor > Melanoma > Nodular melanoma
by Bethany R. Rohr, M.D.
Topic summary: Nodular melanoma (NM) is an aggressive histologic subtype of invasive malignant melanoma; it accounts for 16 – 25.6% of primary cutaneous melanomas. Nodular melanoma mutations overlap with other melanoma subtypes (both low and high cumulative sun damage). Most common in light skinned adults with history of intermittent or chronic sun damage. Pigmented or nonpigmented (pink) papule or nodule with rapid growth; frequently ulcerated. Diagnosis: scoop shave biopsy or excisional biopsy preferred; histopathologic diagnosis is gold standard. Thicker (Breslow) depth is the most important adverse prognosis indicator. Treatment includes excision with or without sentinel lymph node biopsy; additional treatment based on stage.

Soft tissue > Adipose tissue tumors > Liposarcoma > Dedifferentiated liposarcoma
by Susan Potterveld, D.O., M.P.H., Michael R. Clay, M.D.
Topic summary: Well differentiated liposarcoma (WDL) with transition, either in the primary tumor or as a recurrence to a sarcoma that is typically nonlipogenic. Molecularly characterized by ring or giant marker / rod chromosomes composed of material from 12q13-15; results in localized amplification of several neighboring genes, including MDM2. Although these tumors were originally all considered high grade, low grade dedifferentiation is now a recognized phenomenon. Typically occurs in older adults, with a slight predilection for men. Better prognosis than other high grade pleomorphic sarcomas but still recurs in 40 – 75% of cases, metastasizes in 10 – 15% of cases and is associated with a 28% mortality rate. Resectable disease is treated with surgery to obtain negative margins.

22 May 2023: Textbook Updates

We have posted updates of the following topics:

Anus & perianal area > Carcinoma > Neuroendocrine carcinoma
by Raul S. Gonzalez, M.D.
Topic summary: Poorly differentiated neuroendocrine carcinoma arising in the anus. Very aggressive, with early metastatic spread; 5 year survival is ~10%. Similar histology to small cell or large cell neuroendocrine carcinoma at other sites. Represents ~7% of anal carcinomas. Associated with high risk HPV infection, though with low viral copy numbers. Molecular abnormalities often seen in TP53, Rb-E2F pathway. May cause rectal bleeding or present as an anal mass. Radiology: destructive lesion; no features specific to neuroendocrine nature. Diagnosis: tissue sampling. Higher stage confers poor prognosis. Treatment: chemotherapy (often platinum based) and radiation.

Breast > Other invasive carcinoma subtypes, WHO classified > Adenoid cystic
by Gary Tozbikian, M.D.
Topic summary: Triple negative and basal-like subtype of mammary carcinoma with excellent long term survival; histologically similar to salivary gland counterpart. Comprised of epithelial and myoepithelial cells arranged in solid, cribriform or tubular arrangements and associated basement membrane material. MYB::NFIB fusion gene (t(6;9)(q22-23;p23-24)) identified in the majority adenoid cystic carcinomas of breast, as well as in solid variant. Rare, 0.1% of breast carcinomas; may be associated with microglandular adenosis. Mammogram or other imaging detects a mass; diagnosis made by tissue biopsy or resection, often utilizing immunohistochemistry. Treatment is excision with clear margins and possibly radiation; axillary dissection may not be necessary.

Ear > External ear tumors – benign / nonneoplastic > Keloid
by Andrew Dettrick, M.B.B.S., Ruta Gupta, M.D.
Topic summary: Abnormal proliferation of scar tissue that extends beyond the boundaries of the initial injury and does not regress. Very common in dark skinned people (Fitzpatrick skin types 4 – 6); recurrence after excision is common. Keloids and hypertrophic scars are an abnormal response to trauma; wounds more likely to undergo keloid formation include wounds healing by secondary intention, wounds with prolonged inflammation (foreign body, infection, burn, earring site) and sites of repeated trauma. Can usually be diagnosed by visual inspection, palpation and history. Keloid is biologically harmless with no risk of malignant transformation; most eventually stop growing and remain stable or even involute slightly.

Bone marrow neoplastic > Bone marrow – plasma cell and lymphoid neoplasms > Plasma cell neoplasms > MGUS – non-IgM
by Hatem Kaseb, M.D., Ph.D., M.P.H., S. David Hudnall, M.D.
Topic summary: Non-IgM monoclonal gammopathy of undetermined significance (MGUS) is a benign, asymptomatic premalignant plasma cell disorder that is characterized by the presence of serum M protein < 30 g/L, bone marrow clonal plasma cells < 10% and absence of plasma cell myeloma related end organ damage or amyloidosis. Incidence increases with age; more prevalent in African Americans than in Caucasians (2 – 3 fold). Usually diagnosed as an incidental finding on protein electrophoresis performed to evaluate peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia or elevated erythrocyte sedimentation rate. Considered a preneoplastic condition with an annual risk of progression of ~1%.Management requires an understanding of the risk of progression.

Nasal cavity, paranasal sinuses, nasopharynx > Sinonasal adenocarcinoma > Intestinal type
by Vladyslav Ilchenko, M.D., Rifat Mannan, M.B.B.S., M.D.
Topic summary: Sinonasal intestinal type adenocarcinoma (ITAC) is an epithelial tumor of the nasal cavity and the paranasal sinuses, often related to professional exposure to organic dust (such as wood or leather). A characteristic feature of this tumor is an increased production of intracellular or extracellular mucin, similar to mucinous adenocarcinoma of the intestinal tract. M:F ratio can vary from 4:1 to 21:1 in different geographical regions with a median age of 60 – 65 years. Locally aggressive with ~50% local recurrence; locoregional / distant metastasis occurs in 10 – 20% cases. Mean disease free survival is 32 months. Standard treatment is surgical resection, with a minimally invasive endoscopic approach when possible.

18 May 2023: Textbook Updates

We have posted updates of the following topics:

Breast > Inflammatory / infectious > Benign breast implant related changes
by Tiffany Javadi, M.D., Di (Andy) Ai, M.D., Ph.D.
Topic summary: Saline and silicone breast implants are suitable for use in augmentation mammaplasty and breast reconstruction following mastectomy. Implant related changes include dense fibrosis, chronic inflammation / granulomatous reaction, calcification and synovial metaplasia. Immune recognition of breast implants as foreign results in inflammatory response, leading to the formation of scar (capsule) around the implant, which may contract and cause the implant to feel hard or change shape. Breast implant related changes can lead to other complications, such as implant rupture or displacement and breast implant associated anaplastic large cell lymphoma (BIA-ALCL) in the context of textured implants. Surgical excision is the choice of treatment for capture contracture; implant replacement is the choice of treatment for silicone implant leakage.

Cervix > Premalignant / preinvasive lesions – cytology > Atypical glandular cells (cyto)
by Joseph Reznicek, M.D., Bonnie Choy, M.D.
Topic summary: Atypical glandular cells encompass a broad and challenging differential diagnosis and include entities such as atypical endocervical cells and atypical endometrial cells. Atypical glandular cells fall under the Bethesda system general diagnostic heading of epithelial abnormalities, glandular. High grade lesions are identified in 10 – 40% of AGC cytology cases on follow up: squamous lesions (high grade squamous intraepithelial lesion [HSIL] / cervical intraepithelial neoplasia [CIN] grade 2 – 3) occur more often than glandular lesions; HSIL and adenocarcinoma in situ (AIS) frequently coexist. Management guidelines are per the 2019 ASCCP Risk Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors.

Penis & scrotum > Other tumors > Myointimoma
by Khaled Sabry Mohamed, M.D., Samer Z. Al-Quran, M.D.
Topic summary: Benign myointimal proliferation with predilection to the corpus spongiosum of the glans penis. Intravascular proliferation of the vascular intimal cells; lesional cells stain with α smooth muscle actin but not desmin. Mesenchymal tumor unrelated to the status of circumcision, history of trauma or the presence of disease. Small, distinct, nonmobile, firm, painless nodule on the glans penis. Rare tumor with ~28 cases reported in the literature; wide age range (2 – 74 years old). Diagnosis: laboratory tests, including urine analysis and ultrasonic evaluation of the abdomen and the scrotum to exclude other potential causes. Benign outcome with no recurrence; spontaneous regression may occur. Treatment: simple excision.

Salivary glands > Cytology > Milan system > Nondiagnostic
by Jen-Fan Hang, M.D.
Topic summary: Fine needle aspiration (FNA) with insufficient diagnostic material to provide an informative interpretation (ideally > 60 lesional cells for adequate evaluation); 18.2% of all salivary gland FNA. Estimated risk of malignancy (ROM) by the Milan system: 25%; Real world risk of malignancy: 15.7% (FNA with surgical follow up), 4.1% (overall). Palpation guidance without ultrasound, inadequate sampling determined by rapid on site evaluation and lesions with cystic, vascular or diffuse nature are significantly associated with nondiagnostic results. Treatment: clinical / radiologic follow up only (56%), direct surgery (19%) and repeat FNA (19%).

Uterus > Other tumors > Adenomatoid tumor
by Laura Hang, M.D., Ayse Ayhan, M.D., Ph.D., Amanda L. Strickland, M.D.
Topic summary: Benign tumor composed of mesothelium and smooth muscle. Commonly asymptomatic: typically present as subserosal or intramural small, solitary nodule, usually an incidental finding in resection specimen for unrelated disease; could raise diagnostic difficulties, as morphology may overlap with various differential diagnoses. Found in women of reproductive age; 1.2% of hysterectomy specimens (5% of uterine surgical specimens but true incidence may be higher due to misdiagnosis and missed diagnosis). Neoplastic rather than reactive (based on molecular, clinical and pathological features). Benign tumor with excellent prognosis; no evidence that these tumors impair fertility. Treatment: surgical removal (hysterectomy or rarely, simple excision); excision is adequate treatment.

15 May 2023: Textbook Updates

We have posted updates of the following topics:

Molecular markers > NGS-general
by Meghan Lindstrom, M.D., Emily M. Hartsough, B.S., Pawel Mroz, M.D., Ph.D.
Topic summary: Next generation sequencing (NGS) is a high throughput technique that allows for the sequencing of millions of nucleic acids simultaneously in parallel. Different methods of NGS are primarily divided into short read (pyrosequencing, sequencing by synthesis, sequencing by ligation, ion torrent) and long read (single molecule real time sequencing, nanopore sequencing). Efficiency and cost effectiveness of NGS methods have largely eclipsed Sanger sequencing in clinical and research settings. Other advantages of NGS: improved resolution, algorithms are available that can detect structural variants. Disadvantages of NGS: shorter read lengths, decreased raw accuracy in certain areas, high start up costs. Clinical applications of NGS: oncology testing, germline testing, microbiology, pharmacogenomics.

Soft tissue > Vascular > Nonneoplastic > Papillary endothelial hyperplasia
by Laura Warmke, M.D., Jeanne Meis, M.D.
Topic summary: Benign, reactive proliferation of endothelial cells (nonneoplastic); 3 types: primary (pure form) arising in a dilated vessel, secondary (mixed form) arising in a pre-existing vascular lesion and rare extravascular form typically arising in hematoma. Small, well circumscribed lesion without necrosis, marked cytologic atypia or infiltrative growth pattern; associated thrombotic material is frequently present. Also known as Masson tumor. No known ethnic predilection; average age: 31 years (range, 9 months to 78 years). Intravascular location is most common; can occur in any blood vessel. May represent an alteration in the process of thrombosis. Benign clinical course; secondary form follows course of pre-existing vascular lesion. Treated by simple local excision.

Stains & CD markers > CD103
by Moiz Vora, M.D., Maurice Richardson, M.D.
Topic summary: CD103 is a heterodimeric transmembrane surface receptor that is expressed by several cell types of the immune system and is involved in cell to cell or cell to matrix interactions; mediates cell adhesion, migration and lymphocyte homing through interaction with E-cadherin, which is expressed in epithelial cells. Diagnostic tool in the detection of hairy cell leukemia (HCL) and hairy cell variant (HCL-v); aids in distinguishing hairy cell leukemia from other types of B cell lymphoproliferative disorders (in conjunction with additional markers). Membranous (primarily) and cytoplasmic (variable intensity) with overlay of irregular cytoplasmic borders (consistent with projections). High CD103+ tumor infiltrating lymphocyte cell count is reported to be a favorable prognostic marker in a multitude of solid tumors.

Thyroid & parathyroid > Other uncommon lesions / neoplasms > Solitary fibrous tumor
by Truong Phan Xuan Nguyen, M.D., Huy Gia Vuong, M.D., Ph.D.
Topic summary: Solitary fibrous tumor (SFT) of the thyroid is a fibroblastic mesenchymal neoplasm characterized by NAB2::STAT6 gene fusion; indistinguishable from pleural or other extrapleural solitary fibrous tumors. Fibroblastic tumor composed of collagen producing spindle cells arranged in a characteristic vascular pattern. Rare tumor in thyroid; < 0.1% of SFTs arise in the head and neck area. Age ≥ 55, tumor size ≥ 10 cm, mitotic count ≥ 4/10 high power fields, tumor necrosis ≥ 10% are unfavorable prognostic factors in SFTs of all anatomic sites. Treatment: total thyroidectomy or lobectomy. Roles of chemotherapy or radiation therapy are controversial; close follow up after surgery seems to be the most commonly used approach.

Transfusion medicine > Blood bank testing > Automation
by Raisa Balbuena-Merle, M.D., M.H.S.
Topic summary: Solitary fibrous tumor (SFT) of the thyroid is a fibroblastic mesenchymal neoplasm characterized by NAB2::STAT6 gene fusion; indistinguishable from pleural or other extrapleural solitary fibrous tumors. Fibroblastic tumor composed of collagen producing spindle cells arranged in a characteristic vascular pattern. Rare tumor in thyroid; < 0.1% of SFTs arise in the head and neck area. Age ≥ 55, tumor size ≥ 10 cm, mitotic count ≥ 4/10 high power fields, tumor necrosis ≥ 10% are unfavorable prognostic factors in SFTs of all anatomic sites. Treatment: total thyroidectomy or lobectomy. Roles of chemotherapy or radiation therapy are controversial; close follow up after surgery seems to be the most commonly used approach.

11 May 2023: Textbook Updates

We have posted updates of the following topics:

Cervix > General > Anatomy
by Nada Mohamed, M.D., Jaya Ruth Asirvatham, M.D.
Topic summary: The cervix is the lowest, cylindrical / fusiform part of the uterus that connects the body of uterus (corpus uteri) to the vagina and is composed of 2 regions, the endocervical canal and ectocervix. Endocervical canal is lined by columnar mucinous epithelium; ectocervix is distal, projects into the vagina and is lined by stratified squamous epithelium. Squamous epithelium meets the glandular epithelium at the squamocolumnar junction (SCJ). Epithelium between the 2 sites of the SCJ is called the transformation zone (TZ); cervical cancer mostly originates from this region. Identification of the transformation zone (TZ) is very important during colposcopy; SCJ frequently disappears up into the endocervical canal in the postmenopausal period and may no longer be visible on colposcopic examination.

CNS nontumor > Movement disorders > Multiple system atrophy
by Emile Pinarbasi, M.D., Ph.D., Andrew Lieberman, M.D., Ph.D.
Topic summary: Multiple system atrophy (MSA) is a sporadic, neurodegenerative disease with core clinical features of parkinsonism, autonomic dysfunction and cerebellar ataxia. Pathologically defined by widespread frequent alpha-synuclein glial cytoplasmic inclusions (GCIs) and striatonigral or olivopontocerebellar degeneration. Incidence of 3 – 4 per 100,000 person years; usually presents between fourth and sixth decades. Predominantly sporadic, although rare familial cases reported. Average survival time is 7 – 9 years from diagnosis; patients with disease onset before age 40 may have longer survival. No disease modifying or neuroprotective therapies are available; treatment is aimed at symptomatic relief, with physical therapy and occupational therapy as mainstay.

Kidney nontumor / medical renal > Infection > Chronic pyelonephritis
by Saman Karimi, M.D., M.S., Suman Setty, M.B.B.S., Ph.D.
Topic summary: Diffuse, patchy tubulointerstitial inflammation and scarring accompanied by blunting of calyces and the renal pelvis. Atrophic renal tubules with thyroidization and intraluminal colloid-like proteinaceous casts. Common in pediatric population with congenital anomalies and vesicoureteral reflux disease. Pathophysiology: reflux of urine and ascending infection into the renal pelvis; obstructive uropathy; vesicoureteral reflux. Slow progression, > 2 decades before consequences of damage are observed; can lead to end stage renal disease. Treatment: surgical intervention (correction of anatomic / congenital abnormalities resulting in reflux); medical management (antimicrobial therapy for treatment of recurrent, acute pyelonephritis).

Ovary > Other carcinomas > Mesonephric-like adenocarcinoma
by Doaa Atwi, M.D., Lewis A. Hassell, M.D.
Topic summary: Mesonephric-like adenocarcinoma (MLA) is a rare subtype of gynecologic malignancy with high risk of recurrence and increased tendency to metastasize. MLA shares morphologic, immunophenotypic and molecular characteristics with mesonephric adenocarcinoma (MA) except that mesonephric remnants are not identified in the former. Morphologic hallmark is the combination of architectural patterns in a tumor without squamous or mucinous differentiation; intraluminal dense eosinophilic secretions can be seen. More commonly seen in postmenopausal patients. Sites: uterine corpus and ovary. Surgical approach with total hysterectomy and bilateral salpingo-oophorectomy, with or without pelvic and para-aortic lymph node dissection, is the primary therapy.

Soft tissue > Adipose tissue tumors > Liposarcoma > Atypical lipomatous tumor / well differentiated liposarcoma
by Susan Potterveld, D.O., M.P.H., Michael R. Clay, M.D.
Topic summary: Locally aggressive mesenchymal tumor composed of mature adipocytes and stromal cells with at least focal cytologic atypia. Low grade lipogenic tumor with multiple morphologic subtypes and significant histologic variability. Use of the terminology atypical lipomatous tumor (ALT) and well differentiated liposarcoma (WDL) is based on a tumor’s location in the body and primarily relates to resectability. Most common adipocytic malignancy (40 – 45% of all liposarcomas); peak age in adults is between 40 – 60 years. Most important prognostic factor is anatomic location. Surgical resection with widely negative margins is generally curative; retroperitoneal or central body site tumors are difficult to resect with a clear margin, frequently recur, can dedifferentiate and cause death.

8 May 2023: Textbook Updates

We have posted updates of the following topics:

Appendix > Benign tumors > Tubular adenoma
by Subramanya Sakaleshpura Mallikarjunappa, M.B.B.S., M.D., Raul S. Gonzalez, M.D.
Topic summary: Polypoid dysplastic lesion in the appendix, analogous to conventional adenomas in the colorectum. Tubulovillous adenomas are often resected as mass lesions, while small tubular adenomas may be encountered incidentally in colectomy specimens from patients with polyposis syndromes. Uncommon; identified in 0.02 – 0.06% of appendectomy specimens. Often asymptomatic but may cause appendicitis; other clinical manifestations include intussusception and bowel obstruction. Appendiceal adenocarcinoma can arise from adenomas; risk of progression likely increases with size and high grade dysplasia (as in the colon) but data are limited. Appendectomy alone is generally considered adequate for most benign appendiceal lesions, including adenoma.

Autopsy & forensics > General > Forensic heart dissection
by Sarah C. Thomas, M.D., M.S., Lorenzo Gitto, M.D.
Topic summary: Heart dissection is a medical procedure whereby a pathologist examines and dissects the heart of a deceased individual to determine the cause of death or any underlying heart conditions. Cardiovascular disease accounts for most natural deaths in the medical examiner / coroner’s office. Multiple heart dissection techniques exist: short axis, blood flow (or inflow – outflow), 4 chambers, base of the heart; each dissection technique allows for examination of specific heart regions or disease. Serial sectioning: most common coronary dissection technique; longitudinal dissection: can be done in young subjects when there are no concerns for coronary diseases; removal of the coronary arteries from the heart: useful in case of severely atherosclerotic and calcified vessels.

Kidney tumor > Childhood tumors > Cystic partially differentiated nephroblastoma
by Daniel Athanazio, M.D., Ph.D.
Topic summary: Cystic partially differentiated nephroblastoma is a multilocular, exclusively cystic neoplasm of very young children, containing nephroblastomatous tissue. Lacks solid nodules on gross or microscopic examination; septa contain (undifferentiated) mesenchyme, blastemal and immature epithelial elements. Rare (21 out of 5,100 cases of nephroblastoma); occurs in children presenting before 2 years of age. Diagnosis requires microscopic examination of resected tumor. Rare recurrences have been reported as a complication of incomplete resection or tumor rupture. Surgery is almost always curative: patients with stage I disease are cured by surgery without adjuvant chemotherapy; questionable value of chemotherapy in cases of tumor rupture and spillage.

Larynx, hypopharynx & trachea > Other malignancies > Neuroendocrine neoplasm
by Ziyad Alsugair, M.D., Nazim Benzerdjeb, M.D., Ph.D.
Topic summary: Neuroendocrine neoplasms are composed of neuroendocrine epithelial neoplasms that arise in the larynx and are either well differentiated or poorly differentiated (high grade). These are the second most common group of neoplasms of the larynx after squamous cell carcinomas. Diagnosis is based on tissue examination findings of typical histologic and immunohistochemical features. 5 year survival rate: well differentiated neuroendocrine neoplasms (NET) – variable prognosis and based on the presence of distant metastasis and lymph node metastases; poorly differentiated neuroendocrine carcinomas (NEC) – 5 – 20%. Treatment: G1 NET – local resection; G2 NET – radical surgical resection, elective neck dissection and radiotherapy; NEC regardless of subtype – radiotherapy and chemotherapy.

Prostate gland & seminal vesicles > Atypical / intraductal lesions > Atypical intraductal proliferation
by Kenneth A. Iczkowski, M.D.
Topic summary: Atypical intraductal proliferation (AIP) of the prostate is a gland space containing a usually cribriform arrangement of cells that have mild to moderate atypia, bounded by at least a partial basal cell layer. AIP is a continuum of proliferations, mostly (90%) cribriform in which a distinction is not possible between high grade prostatic intraepithelial neoplasia (HGPIN) and intraductal carcinoma of prostate (IDC). Mean age: 65; mean serum PSA: 8. Compared to prostatectomy with high grade PIN, AIP was associated by multivariate analysis with higher Gleason score, larger tumor volume and more advanced stage. If there is concomitant invasive carcinoma on biopsies, definitive treatment or active surveillance is needed; if the AIP finding is isolated on biosies, repeat biopsy is advisable.