2 February 2023: Textbook Updates

We have posted updates of the following topics:

Colon > Infectious colitis > Intestinal spirochetosis
by Giby V. George, M.B.B.S., Aaron R. Huber, D.O.
Topic summary: Colonization of the colonic epithelium by the filamentous nontreponemal anaerobic spirochetes, Brachyspira aalborgi or Brachyspira pilosicoli. Most commonly asymptomatic but may present with diarrhea or abdominal pain / cramps. Human intestinal spirochetosis (HIS) has a global distribution and Brachyspira species have been detected on nearly every continent, with the exception of Antarctica. Pathogenesis, transmission and risk factors remain unclear. Gold standard for diagnosis is histologic examination of an endoscopic colon or rectal biopsy. Metronidazole is the most commonly utilized antibiotic for symptomatic patients; symptoms will resolve in the majority of patients (81%).

Gallbladder & extrahepatic bile ducts > Gallbladder nonneoplastic > Cholesterolosis
by Reem Hamasha, M.D., Raul S. Gonzalez, M.D.
Topic summary: Accumulation of lipids (triglycerides, cholesterol precursors and cholesterol esters) within subepithelial macrophages in the lamina propria of the gallbladder. Focal, diffuse or polypoid (polypoid cholesterolosis = cholesterol polyps). Also known as strawberry gallbladder. Seen in 10 – 30% of cholecystectomies; occurs in female patients 75% of the time and associated with high BMI. Asymptomatic, noninflammatory; no malignant potential. Incidentally found during abdominal sonography (appears as a pseudopolyp) or diagnosed on histopathology of surgical specimens; microscopic examination provides the definitive diagnosis. Treatment: cholecystectomy.

Skin nonmelanocytic tumor > Adnexal tumors > Sebaceous glands > Nevus sebaceus of Jadassohn
by Ronan Knittel, M.D., Nima Mesbah Ardakani, M.D.
Topic summary: Nevus sebaceus of Jadassohn (sebaceous nevus, organoid nevus) is a hamartoma that is histologically characterized by a complex and abnormal proliferation of epidermis and adnexal structures. Commonly presents at birth as a single yellow patch of alopecia on the scalp, becomes verrucous during childhood and puberty and shows variable enlargement during adulthood (due to development of a range of often benign and seldom malignant tumors). Nevus sebaceus is now considered as a mosaic RASopathy with postzygotic somatic mutations of the Ras protein family, mainly due to HRAS and rarely KRAS mutations, in a section of the skin. Generally, nevus sebaceus will follow a benign course. Generally safe to observe; surgical excision as a cosmetic procedure or to remove a secondary neoplasm.

Transfusion medicine > Therapeutic apheresis > ASFA guidelines overview
by Muharrem Yunce, M.D., Mrigender Singh Virk, M.D.
Topic summary: Apheresis is a modality in which the blood of a person is passed through a device that separates blood into different components, removes 1 constituent and returns the rest, with or without a replacement fluid. American Society for Apheresis (ASFA) publishes guidelines to systematically review the available evidence and provides a categorical way to approach the request of apheresis procedures in different diseases. ASFA guidelines organize diseases and their therapies into category and grading systems; category describes the efficacy and priority of apheresis in treatment of a disease while grading describes the quality of evidence to support apheresis treatment of a disease.

30 January 2023: Textbook Updates

We have posted updates of the following topics:

Cervix > Premalignant / preinvasive lesions – cytology > ASC-H
by Joseph Reznicek, M.D., Bonnie Choy, M.D.
Topic summary: Atypical squamous cells – cannot exclude high grade squamous intraepithelial lesion (ASC-H) refers to cytologic changes that are suggestive of high grade squamous intraepithelial lesion (HSIL) but insufficient for a definitive interpretation. Accounts for 0.3% (median) of all Pap test results; represents < 10% of all ASC interpretations. Sites: cervix, vagina, anus. HPV testing may be used as part of screening, triage and surveillance. Differential diagnosis includes HSIL as well as changes that are not related to human papillomavirus (HPV) infection and neoplasia (e.g., squamous metaplasia, atrophy and intrauterine device [IUD] effect).

Cervix > General > Embryology
by Nada Mohamed, M.D., Jaya Ruth Asirvatham, M.D.
Topic summary: The upper third of the vagina, the cervix, the uterus and both fallopian tubes are derived from the paramesonephric / Müllerian ducts. Deviations from normal development (e.g., abnormal formation, fusion or resorption of Müllerian ducts) result in anomalies. The traditional hypothesis states that the Müllerian ducts are fused in a caudal cranial direction; an alternative hypothesis indicates that fusion and resorption start at the isthmus and proceed bidirectionally at the same time or in a segmental pattern. Müllerian anomalies can be asymptomatic or manifest as amenorrhea, infertility, dyspareunia, repeated miscarriage, complicated pregnancy or difficult labor. Some Müllerian malformations can be treated by corrective surgery.

Oral cavity & oropharynx > Inflammatory / immune mediated (noninfectious) > Lichen planus
by Mark Mintline, D.D.S., Molly Housley Smith, D.M.D.
Topic summary: Chronic, T cell mediated inflammatory mucocutaneous disorder of uncertain etiology and pathogenesis. Common oral mucosal disease with multifocal, bilateral and symmetrical involvement; characterized by white, lace-like lesions (Wickham striae) with or without atrophic or erosive areas. Most commonly seen in middle aged adults. Oral lichen planus is characterized by relapses and remissions; uncertain malignant potential: small subset of patients with oral lichen planus (1.1%) develops oral squamous cell carcinoma. Reticular oral lichen planus is often asymptomatic and no treatment is needed; erosive oral lichen planus is often bothersome due to open sores and is typically managed with topical or systemic corticosteroids.

Skin nontumor > Alopecia > Central centrifugal cicatricial alopecia
by Janelle Welch, M.B.B.S., Jonathan D. Ho, M.B.B.S., D.Sc.
Topic summary: Central centrifugal cicatricial alopecia (CCCA) is a lymphocytic scarring alopecia that predominantly affects women of African descent. Hair loss starts on the scalp vertex and progresses outward in a centrifugal and symmetric pattern. Pathophysiology: incompletely understood; likely results from a combination of external insults to hair and genetic susceptibility. Hair regrowth is possible in the early inflammatory stage; stabilization rather than regrowth is the aim in advanced disease. Treatment: topical corticosteroids, topical calcineurin inhibitors, intralesional steroid injections, oral tetracycline antibiotics (e.g., doxycycline), hydroxychloroquine, cyclosporin, minoxidil, topical metformin.

Skin nonmelanocytic tumor > Neural tumors > Granular cell tumor
by Jarish Cohen, M.D., Ph.D., Philip LeBoit, M.D.
Topic summary: Dermal or subcutaneous tumor with abundant granular cytoplasm and Schwannian differentiation. A predominantly dermal based tumor composed of cells with abundant eosinophilic to basophilic granular cytoplasm. Common sites are trunk, upper limbs and head / neck; may also arise on feet, hands, anogenital region and breast. Dysregulation of endosomal pH due to inactivation of accessory proteins of the vacuolar H+ ATPase can give rise to conventional granular cell tumors. Harboring multiple tumors has been associated with Noonan syndrome and LEOPARD syndrome. Benign and malignant tumors are typically treated with wide local excision; Mohs micrographic surgery is an option for anatomic sites in which conservative re-excision is desired.

26 January 2023: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Congenital anomalies > Urachus and patent urachus
by Bohdan Zoshchuk, M.D., Maria Carolina Beeter, M.D., Y. Albert Yeh, M.D., Ph.D.
Topic summary: The urachus, a fibrous cord connecting the umbilicus to the anterosuperior aspect of the bladder dome, usually obliterates at birth and becomes the median umbilical ligament; urachal pathology results from failure of involution of the embryonic structures, resulting in the formation of a urachal cyst, umbilical urachal sinus, vesicourachal diverticulum or patent urachus – completely patent, tubular remnant communicating the developing bladder and the umbilical cord. Rare in adults, urachal anomalies usually involute in early childhood; M:F = 2:1. Complications of patent urachus: recurrent urinary infections and omphalitis; higher risk of urachal cancer in adults with an estimated incidence of 0.18 per 100,000. Surgical excision (open or laparoscopic) for patent urachus, urachal remnants and symptomatic patients; incision and drainage and antibiotics for infected umbilicus.

Esophagus > Esophagitis > Herpes simplex esophagitis
by Ruchi Patel, M.B.B.S., M.D., James Mueller, M.D., Ph.D.
Topic summary: Infectious esophagitis is the second most common cause of esophagitis after gastroesophageal reflux disease (GERD). More commonly occurs after reactivation of latent HSV with spread of virus to the esophageal mucosa by way of the vagus nerve or by direct extension of oral – pharyngeal infection into the esophagus. Endoscopic findings include multiple discrete or coalescent small ulcers, which may be superficial, punched out or volcano-like in appearance. Confirmation of the diagnosis is obtained by histology or viral culture of esophageal specimens; IHC stain is only required when histologic features are equivocal. Prognosis: overall good; disseminated disease is rare but may be fatal. Treatment is always indicated in immunosuppressed patients.

Lung > Other carcinomas > NUT carcinoma
by Kyriakos Chatzopoulos, M.D., Ph.D.
Topic summary: NUT carcinoma is an aggressive malignancy characterized by NUT gene rearrangements. Morphologically it shows diffuse architecture and consists of monotonous cells with frequent cytoplasmic clearing, large nuclei with prominent nucleoli and foci of abrupt keratinization. Sites: mediastinum, upper aerodigestive tract, occasionally salivary glands, retroperitoneum, pancreas, urinary bladder. Definitive environmental or infectious etiology is lacking. Poor prognosis, with median survival from initial diagnosis ranging 1 – 6.7 months. Surgical options may be limited because of surgical inaccessibility of tumors, particularly those with thoracic anatomic localization; radiotherapy seems to produce superior outcomes compared with conventional chemotherapy.

Pancreas > General > Grossing
by Hulya Sahin Ozkan, M.D., Olca Basturk, M.D.
Topic summary: This topic describes how to gross specimens obtained from pancreaticoduodenectomy, distal pancreatectomy and total pancreatectomy procedures. Sections to obtain: tumor, margins, lymph nodes, nontumoral adjacent organs. Distinguishing common bile duct (CBD) and pancreatic duct (PD): CBD is a large, tan to light yellow colored (bile stained) duct exhibiting numerous punctuate orifices of the peribiliary glands; PD is a narrow, tan-white colored duct with a smooth and glistening luminal surface. Taking gross images of the specimen in both fresh and fixed states is helpful for microscopic examination and reporting.

Stomach > Other nonneoplastic > Iron pill gastritis / pill gastritis
by Satyapal Chahar, M.D., Monica T. Garcia-Buitrago, M.D.
Topic summary: Corrosive injury to gastric mucosa secondary to oral iron supplement intake. Oral iron supplements have been widely used for the treatment of iron deficiency anemia; in 2019, global anemia prevalence was 29.9% in women of reproductive age. Deposition of brown-black inorganic iron crystals on the surface and formation of reactive oxygen metabolites that have corrosive, thrombotic and inflammatory properties. Clinical features: nausea, vomiting, epigastric pain, coffee ground emesis, melena. Diagnosis: upper endoscopy with biopsy. This pathologic process can be reversed by discontinuing use of the oral iron supplement; switch to less toxic form, such as liquid iron preparation or intravenous iron supplementation.

23 January 2023: Textbook Updates

We have posted updates of the following topics:

CNS nontumor > CNS myelin disorders > Multiple sclerosis
by Rachel A. Multz, M.D., Jared T. Ahrendsen, M.D., Ph.D.
Topic summary: Chronic, inflammatory demyelinating disease that may involve any part of the central nervous system. Female predominant neurologic disorder consisting of episodic nervous system dysfunction and characteristic radiologic findings that demonstrate both dissemination in time (multiple episodes) and dissemination in space (multiple lesions seen on imaging). Most frequent cause of nontrauma related permanent disability in young adults. Cause of MS is unknown, though it is favored to be due to an autoimmune activation of lymphocytes. There are no consistently reliable prognostic factors for MS and outcomes for MS patients cannot be accurately predicted; generally, patients with relapsing and remitting courses have a better prognosis than those with progressive forms of the disease.

Lung > Mesenchymal tumors > Pulmonary artery intimal sarcoma
by Atreyee Basu, M.D., Fang Zhou, M.D.
Topic summary: Malignant mesenchymal tumor arising from large pulmonary blood vessels. Found in 1 – 4% of pulmonary endarterectomy specimens in patients with clinical features of chronic thromboembolic pulmonary hypertension; females affected more than males (M:F = 0.7:1). Arises from intimal layer of elastic arteries, usually sparing media. Frequent amplifications and gains as well as other alterations, in 12q12-15, 4q12, 7p12 and others, where several genes, including MDM2, CDK4, PDGFRA, EGFR and other genes, are located. Generally poor survival: median survival, untreated is as low as 1.5 months (range 1.5 – 5.5 months); median survival, if resected: 10 months.

Microbiology, parasitology & COVID-19 > Atypical bacteria > Spirochetes > Leptospira
by Amaro Nunes Duarte-Neto, M.D., Ph.D.
Topic summary: Leptospirosis is caused by pathogenic species of Leptospira, a gram negative bacteria. Febrile jaundice with acute kidney injury, pulmonary hemorrhage, myositis. Endemic in Latin America, Asia with periodic seasonal peaks of cases. Pathophysiology: direct damage by pathogenic Leptospira to hepatocytes and Kupffer cells, associated with host immune response causing hepatitis; vasculopathy and coagulopathy leading to visceral hemorrhages; multiorgan dysfunction. Microscopic agglutination test (MAT) is the confirmatory test. Markers of unfavorable prognosis: renal dysfunction, elevated potassium, pulmonary hemorrhage, severe hypoxemia, shock; complete recovery in those who survive.

Prostate gland & seminal vesicles > Acinar / ductal adenocarcinomas > Adenocarcinoma with aberrant p63
by Kenneth A. Iczkowski, M.D.
Topic summary: A small subset of prostatic acinar carcinoma is characterized by strong p63 nuclear immunoexpression; distinctive morphologic and molecular phenotypes have been described in these cases. Besides atrophic-like change, salient features that have been described include a basaloid appearance and high N:C ratio, with multilayered and sometimes spindled nuclei. Immunostains for cytokeratin 34 beta E12 (negative) and AMACR / P504s (positive) can help resolve problematic foci. Serum PSA elevation is a usual feature. Most but not all cases seem to have favorable pathology; long term outcome has not been studied yet.

12 January 2023: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Urothelial carcinoma – invasive > Lymphoepithelioma-like
by Daniel Anderson, M.D., M.B.A., Maria Tretiakova, M.D., Ph.D.
Topic summary: Rare subtype of urothelial carcinoma that occurs throughout the urinary tract. It resembles nonkeratinizing nasopharyngeal carcinoma, undifferentiated subtype (previously known as lymphoepithelioma) but is EBV negative, in contrast to the nasopharyngeal tumor. M:F = 2.8:1; occurs in late adulthood, mean age of 70 years (range: 54 – 84 years). Essentially an H&E diagnosis with demonstration of characteristic findings of pleomorphic cells with syncytial growth and associated inflammatory infiltrate. Some authors report a more favorable prognosis and better response to systemic chemotherapy when pure or predominant (> 50%). No clear treatment guidelines; one study suggests that a combination therapy including radical cystectomy could possibly yield the best outcome of disease free survival.

Breast > Other carcinoma subtypes, WHO classified > Tubular
by Pragya Virendrakumar Jain, M.D., Julie M. Jorns, M.D.
Topic summary: Special subtype of invasive breast carcinoma with favorable prognosis. > 90% of the tumor is composed of ovoid or angular tubules with open lumina lined by a single layer of epithelial cells with low grade nuclei and sparse mitoses (grade 1). Occurs in postmenopausal women, median age at presentation is 63 years. Mammography: may present as a discrete or ill defined mass with well demarcated or spiculated, irregular margins, respectively or as an architectural distortion, with variable calcifications. Well differentiated variant with very favorable prognosis (low rates of recurrence and metastasis). Treatment: surgery, either breast conserving surgery (lumpectomy) or mastectomy, with or without radiation therapy depending on surgery and clinical features.

Cervix > Benign / nonneoplastic epithelial lesions > Lobular endocervical glandular hyperplasia
by Adam Lechner, B.M., Carlos Parra-Herran, M.D.
Topic summary: Rare lesion of the cervix characterized by a proliferation of discrete lobules of small, round glands showing gastric type differentiation. Benign, although frequent association with underlying malignancy poses a challenge for management. Constellation of features on MRI and Pap smear can yield reasonably high suspicion; however, histologic evaluation remains necessary for definitive diagnosis and exclusion of occult malignant disease. Treatment: pure LEGH without atypical features, diagnosed on hysterectomy, is considered benign and requires no additional treatment / follow up; if diagnosed on biopsy, cervical LEEP or conization, conduct may vary.

Stains & CD markers > Pit1
by William McDonald, M.D.
Topic summary: Immunostains for anterior pituitary transcription factors, pituitary transcription factor 1 (Pit1), steroidogenic factor 1 (SF1) and T box transcription factor (Tpit) have been shown to have higher sensitivity and specificity than hormone IHC stains  for prolactin, growth hormone and TSH and are often used in conjunction with them to classify pituitary adenomas. Pit1 is expressed in the anterior pituitary gland within normal lactotroph, somatotroph, mammosomatotroph and thyrotroph cells as well as within adenomas showing differentiation along these lines. Nuclear expression is evaluated (reactivity only in the cytoplasm is regarded as negative).

Stomach > Other nonneoplastic > Gastric antral vascular ectasia
by Hunter Monroe, B.S., Tony El Jabbour, M.D.
Topic summary: Antral vascular malformation with dilation of superficial mucosal and submucosal blood vessels, often with associated fibrin microthrombi. Accounts for up to 4% of nonvariceal gastrointestinal bleeding, usually chronic with associated iron deficiency. Strong association with autoimmune disorders (up to 62%) and liver cirrhosis (up to 30%). Esophagogastroduodenoscopy (EGD) is gold standard for endoscopy. Exact mortality is unknown but appears to be low; factors associated with poorer prognosis: hemorrhage, number of comorbidities, Hispanic status, refractory to endoscopic ablation. Treatment: symptom management with blood transfusions and iron supplements; endoscopic ablative treatments are first line.

9 January 2023: Textbook Updates

We have posted updates of the following topics:

Anus & perianal area > Other nonneoplastic > Inflammatory cloacogenic polyp
by Nikka Khorsandi, M.D., Fahire Goknur Akarca, M.D., Kwun Wah Wen, M.D., Ph.D.
Topic summary: Benign polyp with colorectal, squamous and transitional epithelium with thickened and prolapsed muscularis mucosa.Thought to be associated with mucosal prolapse or chronic inflammatory diseases. Wide age range from pediatric to adult population. Rectal mucosal prolapse due to repeated mucosal ischemia and regeneration are thought to contribute to the development. Colonoscopy or sigmoidoscopy typically identifies a sessile or pedunculated polyp. Symptoms range from asymptomatic to rectal bleeding to constipation, tenesmus, anal swelling or anal itching. Benign entity with no increased risk for malignancy. Treatment: endoscopic polypectomy or mucosal resection; high fiber diet.

CNS & pituitary tumors > Sellar region tumors> Pituitary neuroendocrine tumor (PitNET)
by Michael Punsoni, M.D., Sylvia L. Asa, M.D., Ph.D.
Topic summary: Neuroendocrine tumors of the anterior pituitary gland that are composed of secretory cells with pituitary hormone production. Current consensus classifies tumors according to pituitary cell lineage and cell differentiation. Tumor subtypes are predictive of responsiveness to medical therapies; for example, densely granulated somatotroph tumors are usually responsive to long acting somatostatin analogues whereas sparsely granulated somatotroph tumors are not; densely granulated corticotroph tumors tend to respond to pasireotide therapy. Surgical approaches: commonly via transsphenoidal route (minimally invasive); transfrontal approach for larger invasive tumors; partial versus gross total resection.

Lung > Other carcinomas > Large cell
by Emily O. Symes, M.D., Aliya N. Husain, M.D.
Topic summary: Malignant, poorly differentiated epithelial neoplasm of lung composed of large, atypical cells; null or unclear immunophenotype based on IHC analysis with TTF1, p40 and neuroendocrine markers. Diagnosis of exclusion: only resection specimens with exclusion of a differentiated component, via thorough sampling, can be classified as large cell carcinoma. M > F, average age of 65 years, associated with cigarette smoking. Becoming increasingly rare due to immunohistochemical and molecular studies that support the reclassification of entities formerly diagnosed as large cell carcinoma. Generally poor prognosis with limited treatment options. 

Skin melanocytic tumor > Genital and mucosal melanocytic tumors > Mucosal melanoma (genital, oral, sinonasal)
by Mona Deerwester, M.D., M.Sc., Bruce R. Smoller, M.D.
Topic summary: Malignant neoplasm of mucosal melanocytes; rare melanoma subtype that originates from melanocytes within sun protected mucous membranes. Mucosal melanomas represent only ~1.4% of all melanomas; the incidence of mucosal melanomas is higher in Caucasians than other racial groups. Smoking, ill fitting dentures and ingested / inhaled carcinogens, such as tobacco and formaldehyde, are regarded as potential causative factors for oral and sinonasal mucosal melanoma; chronic inflammatory disease, viral infections and chemical irritants are thought to be implicated in vulvar mucosal melanoma. Mucosal melanoma is one of the most aggressive subtypes of melanoma and carries a significantly worse prognosis than cutaneous melanoma with a 5 year overall survival of < 25%; 23% of patients have metastases at the time of diagnosis.

Soft tissue > Smooth muscle > Leiomyosarcoma > Leiomyosarcoma-general
by Borislav A. Alexiev, M.D.
Topic summary: Leiomyosarcoma (LMS) is a malignant mesenchymal tumor showing smooth muscle differentiation. Fascicles of eosinophilic spindled cells with blunt ended nuclei showing variable pleomorphism. Leiomyosarcoma belongs to the group of soft tissue sarcomas with complex and unbalanced karyotypes, which results in severe genomic instability. It has substantial intrinsic aggressiveness and is one of the sarcoma subtypes with the highest risk of distant recurrence and decreased disease specific survival; overall 5 year survival: 68%. Staging of soft tissue sarcomas, including leiomyosarcoma, is important in guiding treatment; leiomyosarcoma should be staged using the TNM staging for soft tissue tumors of the AJCC and UICC.

5 January 2023: Textbook Updates

We have posted updates of the following topics:

Liver & intrahepatic bile ducts > Viral hepatitis > Adenovirus hepatitis
by Vladyslav Ilchenko, M.D., Rifat Mannan, M.B.B.S., M.D.
Topic summary: Adenoviruses are widely distributed viruses that usually cause self limited infections; but in an immunocompromised host they can cause severe infections with injuries to multiple organs, including the liver. It can be either a primary infection or reactivation of latent infection. Diagnosis of adenovirus hepatitis can be made on liver biopsy with confirmation by adenovirus immunostaining. Abdominal CT may reveal small or large hypodense areas in the liver, areas of necrosis. Rapid progression with massive liver necrosis is usually fatal with patients dying secondary to organ failure; surviving patients had limited necrosis at the time of initial diagnosis. Treatment: supportive care; antiviral therapy can be helpful.

Liver & intrahepatic bile ducts > Acute and chronic hepatitis > Chronic hepatitis-grading / staging
by Kimberley J. Evason, M.D., Ph.D.
Topic summary: Chronic hepatitis: liver fibrosis that occurs as a result of hepatocyte based injury and inflammation, most commonly due to viral or autoimmune hepatitis; separate scoring systems should be used for steatohepatitis and biliary disorders. Batts-Ludwig system is the most widely used scale for assessing grade (amount of necroinflammatory activity) and stage (degree of fibrosis) in chronic hepatitis (scale 0 – 4 for grade and stage). Other staging systems include Knodell, Ishak, Scheuer and METAVIR. Pathology report should state which grading and staging system (scale) is used for scoring. 

Oral cavity & oropharynx > Potentially malignant & dysplasia > Proliferative verrucous leukoplakia (PVL)
by Molly Housley Smith, D.M.D.
Topic summary: An oral potentially malignant disorder that shows slow growing, persistent and often multifocal proliferations of white, verruciform lesions of the oral cavity, particularly the gingiva. Shows high rates (~50%) of recurrence and progression to squamous cell carcinoma. Middle aged to older women are most affected. Little is known about the molecular pathways and biologic factors associated with PVL. Diagnosis is made upon clinical examination; however, biopsy is required to determine transformation of hyperkeratotic lesions into cytologic dysplasia or carcinoma.  Although no standard of care exists for treatment, cases of PVL with cytologic dysplasia or those diagnosed as bulky hyperkeratotic epithelial proliferation (with or without suspicion for invasion) are generally excised with conservative, assured margins when clinically feasible.

Skin melanocytic tumor > Congenital nevi and associated neoplasms > Congenital nevus
by Anila Chughtai, M.B.B.S., Saba Anjum, M.B.B.S.
Topic summary: Nevi that are present at birth or that arise within the first few postnatal weeks. Benign lesion characterized by bland melanocytic proliferation in the dermis; melanocytes prominently cluster around dermal appendages and show maturation in the depth. Found in 1 – 2% of newborns, 0.6 – 1.6% of the population; incidence of malignant change has been reported more in females, large nevi and axial lesions. Believed to develop due to unregulated growth of melanoblasts during the fifth to twenty fourth week of gestation. Excellent prognosis. Treatment: surgical excision; other treatment modalities include laser, radiotherapy, dermabrasion, cryotherapy, electrotherapy and chemical peels.

Testis & paratestis > Germ cell tumors > Teratoma with somatic type malignancy
by Christopher Dall, M.D., Debra L. Zynger, M.D.
Topic summary: Testicular germ cell tumor with an area of pure somatic type malignancy that arises from germ cell tumor progenitor cells and occupies ≥ 0.5 cm (approximately ≥ 1 microscopic field using 4x objective). Identified within primary testicular tumor or at a metastatic site; rhabdomyosarcoma, adenocarcinoma, embryonic type neuroectodermal tumor and sarcoma, NOS are the most frequent histologies. If confined to the testis without synchronous metastasis, somatic malignancy does not appear to confer a worse prognosis; presence in a metastatic site is associated with poor survival (median survival: 44 months). Surgical resection is the mainstay of treatment.

22 December 2022: Textbook Updates

We have posted updates of the following topics:

CNS & pituitary tumors > Gliomas, glioneuronal tumors, and neuronal tumors > Neuronal and mixed neuronal-glial tumors > Gangliocytoma & ganglioglioma
by Jared T. Ahrendsen, M.D., Ph.D.
Topic summary: Uncommon, well differentiated, slow growing glioneuronal tumors composed predominantly of neoplastic mature ganglion-like cells (gangliocytoma) or a mixture of neoplastic ganglion-like cells and atypical glial cells (ganglioglioma). Characterized by molecular alterations resulting in activation of the MAPK pathway (BRAF V600E is most common). Predilection for children and young adults (majority are < 20 years old; median age is 12 years) but can occasionally be seen in older patients. Tumors in the cerebrum, especially temporal lobe, are associated with seizures / epilepsy. Ganglioglioma: low grade tumor with excellent overall prognosis (15 year overall survival is 83 – 94%); gangliocytoma: benign tumors with excellent long term survival.

Laboratory Administration & Management of Pathology Practices > Quality management > Validating a new quantitative assay
by Felix Leung, Ph.D.
Topic summary: Proper analytical validation of a new assay is essential prior to patient testing; using Clinical Laboratory Standards Institute (CLSI) guidelines as a framework for designing new assay validations is highly recommended. Minimum requirements for analytical validation of a quantitative assay include studies for precision, bias, accuracy, linearity and reference interval. Establish performance limits for validation studies a priori using appropriate total allowable error goals; laboratory medicine associations have defined total allowable error goals for clinical assays. Statistical programs / software are useful tools to aid the analyses and calculations required for analytical validation studies based on CLSI standards.

Lymph nodes & spleen, nonlymphoma > Lymph node-nonspecific findings > Granulomatous inflammation
by Simon A. Backer, M.D., Sumire Kitahara, M.D.
Topic summary: Specialized immune response against various inflammatory insults, involving chronic activation and organization of mononuclear phagocytic cells (macrophages). Histologically characterized by central epithelioid histiocytes surrounded by acute or chronic inflammation. May be associated with infectious disease or noninfectious disease; no particular predilection for age / sex. Pathophysiology: dysregulation of immune response due to inability of macrophages to clear the offending agent. Prognosis is dependent on etiology (e.g., HIV, sarcoidosis, malignancy, infection). Treatment: management of underlying disease (e.g., infection, neoplasm, inflammatory / autoimmune); removal of offending agent (e.g., removal of foreign body).

Soft tissue > Adipose tissue tumors > Other benign lesions > Lipoblastoma / lipoblastomatosis
by Jamshid Abdul-Ghafar, M.D., Ph.D., Mujtaba Haidari, M.D., Nasir Ud Din, M.B.B.S.
Topic summary: Benign, rapidly growing neoplasm composed of embryonal white fat with variable degrees of myxoid changes. 75 – 90% are seen before the age of 3 years, with male predilection (M:F = 2.8:1). Rapidly growing, painless, soft tissue mass with swelling, common in trunk and extremities. Exhibits pseudodiploid or hyperdiploid karyotypes combined with structural alteration of 8q11-q13, which leads to PLAG1 rearrangement. Standard diagnostic approach is histopathologic examination with immunohistochemistry as an adjunct. Prognosis is favorable: well circumscribed, encapsulated. Treatment: complete surgical excision; no metastasis has been reported.

15 December 2022: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Osteosarcoma > Conventional osteosarcoma and osteosarcoma overview
by Jesse Hart, D.O., Borislav A. Alexiev, M.D.
Topic summary: Malignant tumor of connective tissue (mesodermal) origin within which the tumor cells produce bone or osteoid (tumor bone or tumor osteoid). Permeative and destructive growth pattern. The predilection of osteosarcoma for the age of pubertal growth spurt and the sites of maximum growth suggest a correlation with rapid bone proliferation. Parosteal osteosarcoma: most common surface osteosarcoma; low grade central osteosarcoma: 1 – 2% of osteosarcoma; periosteal osteosarcoma: rare (less common than parosteal osteosarcoma); high grade surface osteosarcoma: rare (< 1% of osteosarcoma); extraskeletal osteosarcoma: rare; usually occurs in adults. Conventional osteosarcoma treatment consists of a combination of neoadjuvant and adjuvant chemotherapy and surgery.

Kidney tumor > Adult renal cell carcinoma – rare > SMARCB1 deficient renal medullary carcinoma
by Daniel Anderson, M.D., M.B.A., Maria Tretiakova, M.D., Ph.D.
Topic summary: Rare, highly aggressive, typically medulla centered carcinoma with SMARCB1 (INI1) deficiency. Occurs predominantly in young patients with sickle cell trait; variety of histologic patterns. Believed to arise from the renal papillae or calyceal epithelium and may be triggered by the chronic medullary hypoxia and hypertonic environment resulting from sickled red cells and microvascular occlusion. Mean age: 26 years (wide age range: 5 – 69 years); M:F = 2:1. Poor prognosis with a median overall survival of 6 – 13 months; metastatic stage at diagnosis increases the risk of death about threefold. Treatment: radical nephrectomy; chemotherapy is usually administered with platinum based regimens.

Molecular markers > MyoD1
by Zhonghua Liu, M.D., Ph.D., Patricia Tsang, M.D., M.B.A.
Topic summary: Located on 11p15.1, MYOD1 (myogenic differentiation 1) encodes myogenic transcriptional regulatory protein expressed in early skeletal muscle differentiation during skeletal muscle development and regeneration. Functions as a transcription factor of the basic helix – loop – helix family and the myogenic factor subfamily, regulating muscle cell differentiation by inducing cell cycle arrest, a prerequisite for myogenic initiation. MYOD1 p.L122R is a recurrent hotspot mutation in spindle cell / sclerosing rhabdomyosarcomas (SRMS) with unfavorable prognosis. Expression of MyoD1 may be seen in a variety of rare tumors with rhabdomyoblastic differentiation, including Wilms tumors, neuroendocrine carcinoma, malignant glial tumors, malignant peripheral nerve sheath tumor, teratoma and melanoma.

Ovary > Clear cell neoplasms > Clear cell borderline tumor
by Lucy Ma, M.D.
Topic summary: Adenofibromatous tumor with clear cells demonstrating low grade cytologic atypia and some degree of glandular crowding but without stromal invasion. No solid, papillary or cribriform growth. Pure clear cell borderline tumors are very rare: < 1% of all ovarian borderline tumors; most patients are postmenopausal (age range of 36 – 82 years old). May be a component of the adenofibromatous pathway of the pathogenesis of ovarian clear cell carcinoma. Associated with endometriosis (~15%). Incidental imaging finding; abdominal / pelvic pain. Definite diagnosis requires extensive sampling. Good prognosis; no clinical evidence of aggressive behavior. Treatment: surgical resection; tumors are typically stage I. 

12 December 2022: Textbook Updates

We have posted updates of the following topics:

Eye > Orbit & optic nerve > Temporal arteritis
by José Tomás Peña, M.D., Pablo Zoroquiain, M.D.
Topic summary: Giant cell arteritis is a systemic and discontinuous nonnecrotizing vasculitis of elastic and muscular arteries. Presents in patients in the sixth decade of life or older with new onset headache. Gender: F:M = 3:1; race / ethnicity: more common in Caucasians; rare in Asian and African American patients. Immune mediated disease of unknown etiology. Diagnosis requires morphologic confirmation. Predictors associated with reduced risk of permanent visual loss: fever, rheumatic symptoms; predictors associated with increased risk of permanent visual loss: age, history of transient visual ischemic symptoms, jaw claudication. Treatment: corticosteroids as soon as possible; can be combined with corticosteroid sparing drugs.

Heart > Benign tumors / other nonneoplastic > Cardiac fibroma
by Shuhei Toba, M.D., Chrystalle Katte Carreon, M.D.
Topic summary: Cardiac fibroma is rare but is also the second most common cardiac tumor in children and may occur in association with basal cell nevus syndrome (BCNS), also known as Gorlin syndrome. Multinodular architecture of cardiac fibromas suggests a multifocal origin of the tumor arising from proliferation of scattered resident stromal fibroblasts / myofibroblasts interspersed between cardiomyocytes from multiple foci, with progressive nodular growth and subsequent formation of a larger and more compact solid tumor mass. Younger age at diagnosis: worse survival; higher incidence of fatal arrhythmias in children < 3 years old. Surgical resection / excision has been shown to cure arrhythmias; heart transplants are sometimes considered and performed, particularly for large tumors that are not amenable to surgical removal.

Informatics, digital & computational pathology > Spectral imaging > Spectral imaging
by Aisha Abdelhafez, M.Sc., Anil Parwani, M.D., Ph.D., M.B.A.
Topic summary: Spectral imaging, commonly referred to as imaging spectroscopy, combines traditional imaging and spectroscopy techniques to gather both spatial and spectral data about an object. Analysis is based on well validated standard spectroscopy algorithms used for identifying, unmixing and quantifying components in mixtures; spectral imaging software essentially modifies such methods to produce pixel by pixel quantitative data. Collection optics (or instruments) includes microscopes, endoscopes, camera lenses and other devices. Spectrum imaging may be helpful in applications where subtle spectral discrepancies exist in chemical components within a scene of spectral images; it has enabled applications in a wide variety of biomedical engineering studies, ranging from specific biochemical species detected in in vitro samples to organs of living individuals.

Liver & intrahepatic bile ducts > Benign / nonneoplastic > Mesenchymal hamartoma
by Bella Lingjia Liu, M.D., Stephen C. Ward, M.D., Ph.D.
Topic summary: Rare, benign hepatic lesion of young children; primitive myxoid mesenchyme with benign dilated or branching bile ducts and clusters of normal appearing hepatocytes. Variable proportions of mixed solid and cystic areas with disorganized arrangement of primitive mesenchyme, benign bile ducts and normal appearing hepatocytes. 80% are diagnosed in patients < 2 years old with a slight male predominance (60 – 70% male). Associated with activation of chromosome 19q13.4 microRNA cluster (C19MC). Complete surgical excision is the best treatment; unresectable cases may require liver transplantation. Excellent prognosis with complete resection; rare malignant transformation to embryonal sarcoma has been described.

Lymphoma & related disorders > Hodgkin lymphoma > Mixed cellularity
by Carmen Bárcena, M.D., Laurence de Leval, M.D., Ph.D.
Topic summary: Subtype of classic Hodgkin lymphoma (CHL) with Hodgkin / Reed-Sternberg (HRS) cells in a nonneoplastic mixed inflammatory background. B cell lymphoma derived from germinal center B cells; HRS cells in a reactive mixed inflammatory microenvironment consisting of small lymphocytes, eosinophils, plasma cells, neutrophils and histiocytes. More common in patients with immunodeficiency and in developing countries. About 90 – 95% of patients with early stage CHL and 80 – 85% with advanced stage CHL are cured. Treatment: intensive polychemotherapy (ABVD or BEACOPP), with or without radiotherapy; for refractory cases, stem cell transplant, brentuximab vedotin, checkpoint inhibitors.