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Snippets in surgical pathology
  1. K Cooper,
  2. R Chetty

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This section features synopses of pertinent practical publications that appear in Pathology journals in the respective sub-specialties. The summaries are mere guidelines and personal opinions of the two authors. The articles selected are diverse but occasionally reflect the authors' bias and are from the more widely read pathology journals. It is not intended to be an assiduous search of every publication in every Pathology journal, but more of a general indication of some of the monthly highlights through the eyes of the authors.

Hopefully, these snippets will provide the reader with enough to glean some facts and tips, as well as encourage them to read the entire article if necessary.

Journal of Clinical Pathology

September 2009

Metias SM, Lianidou E, Yousef GM. MicroRNAs in clinical oncology: at the crossroads between promises and problems. J Clin Pathol 2009;62:771–6.

Very good overview of microRNAs, their involvement in cancer and possible therapeutic applications. Well worth a read.

Llobet D, Pallares J, Yeramian A, et al. Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J Clin Pathol 2009;62:777–85.

This is an excellent summary of the molecular pathways of endometrial carcinoma. Five molecular features characterise endometrioid carcinomas: microsatellite instability, and mutations in the PTEN, k-RAS, PIK3CA and β-catenin genes; non-endometrioid carcinomas show alterations of p53, loss of heterozygosity on several chromosomes and molecular alterations of STK15, p16, E-cadherin and C-erb B2.

Manduch M, Oliveira AM, Nascimento AG, et al. Massive localised lymphoedema: a clinicopathological study of 22 cases and review of the literature. J Clin Pathol 2009;62:808–11.

An entity occurring in morbidly obese adults with a predilection for the thigh and posterior calf/lower leg. Gross appearance is of markedly thickened skin with a cobblestone appearance. Histologically: dermal fibrosis, thickened fibrous septa with increased stromal fibroblasts, lymphatic proliferation and lymphangiectasia, and multinucleated fibroblasts. It is important to bear this diagnosis in mind as it simulates atypical lipoma/well-differentiated liposarcoma. Clinical information is required to clinch the diagnosis of this pseudosarcomatous condition.

Denson JL, Keen CE, Froeschle PO, et al. Adiaspiromycosis mimicking widespread malignancy in a patient with pulmonary adenocarcinoma. J Clin Pathol 2009;62:837–9.

With immunocompromised patients manifesting unusual, never seen before infections (in humans), this is a nice case report describing one such exotic infection: adiaspiromycosis, which is usually a fungal infection of small animals. Histologically, one sees a large circular fungal spore (an adiaspore) with a thick wall divided into a deeply eosinophilic outer zone and a thicker, homogenous, paler, inner zone. The centre appears grey and eosinophilic. The spore elicits a typical granulomatous response. The actual fungus is Emmonsia, and the two main pathogenic subtypes are E parva and E crescens.

International Journal of Gynaecological Pathology

September 2009

Robboy SJ, Shaco-Levy R, Peng RY, et al. Malignant struma ovarii: an analysis of 88 cases, including 27 with extraovarian spread. Int J Gynecol Pathol 2009;28:405–22.

The course of struma ovarii is difficult to predict. This study reviews 88 cases (collaborative and literature experience) demonstrating that the size of the stromal component rather than the overall size of the ovarian teratoma had predictive value: those with a stromal component ≤6 cm in size rarely recurred (7%), while those ≥12 cm were clinically malignant. Only the papillary and poorly differentiated patterns were predictive of outcome. The recurrence of papillary carcinoma occurred at about 4 years on average, while the follicular lesions recurred at about 11 years.

Stewart CJR, Brennan BA, Crook ML, et al. Comparison of proliferation indices in primary adult-type granulosa cell tumours of the ovary and their corresponding metastases: an analysis of 14 cases. Int J Gynecol Pathol 2009;28:423–31.

The prognosis of adult granulosa cell tumours is difficult to predict. A comparison of proliferative indices (mitotic index vs Ki-67 index) was NOT predictive of recurrence. Hence, these tumours continue to be regarded as low grade with a potential for late metastases warranting long-term follow-up.

Molina IBA, Seamon LG, Copeland LJ, et al. Reclassification of leiomyosarcoma as an extra-gastrointestinal stromal tumour of the gynaecologic tract. Int J Gynecol Pathol 2009;28:458–63.

A case originally diagnosed as a leiomyosarcoma proved to be an extraintestinal gastrointestinal stromal tumour (GIST). GIST needs to be borne in mind when dealing with spindle cell tumours of the female genital tract.

Chênevert J, B Tetu, M Plante, et al. Indication and method of frozen section in vaginal radical trachelectomy. Int J Gynecol Pathol 2009;28:480–8.

Vaginal radical trachelectomy (VRT) is a fertility-sparing alternative to radical hysterectomy. This study summarises the long-term experience with frozen section evaluation of the endocervical margin (if <5 mm, additional resection is required), concluding that frozen section should only be performed on VRT with a visible cancer or a non-specific lesion. Perpendicular sections should be employed where the tumour is closest to the margin.

Han CP, Lee MY, Kok LF, et al. Adding the p16INK4a marker to the traditional three-marker (ER/Vim/CEA) panel engenders no supplemental benefit in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray study. Int J Gynecol Pathol 2009;28:489–96.

An interesting tissue microarray study showing that the addition of p16 to the ‘traditional’ three-marker immunopanel of ER/VIM/CEA does NOT add more value to the distinction between endometrial and endocervical adenocarcinoma.

Human Pathology

September 2009

Gilks CB, Prat J. Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 2009;40:1213–23.

The recent advances in the pathology and genetics of ovarian surface epithelial carcinomas are reviewed in this manuscript. Excellent review.

Strosberg J, Nasir A, Coppola D, et al. Correlation between grade and prognosis in metastatic gastroenteropancreatic neuroendocrine tumours. Hum Pathol 2009;40:1262–8.

The grading of neuroendocrine tumours has not been uniformly applied. This study analysed 83 patients (40 biopsies) with gastroenteropancreatic neuroendocrine tumours that metastasised, and correlated grade with survival. A three-tiered system (low, intermediate and high-grade) was assigned based on mitotic rates and the Ki-67 index: low-grade (G1) tumours are defined by a mitotic rate of less than 2 per 10 high-power fields (HPFs) and/or Ki-67 index of 2% or less; intermediate-grade (G2) tumours are defined by 2–20 mitoses per 10 HPFs and/or Ki-67 index between 3% and 20%, and high-grade (G3) carcinomas are defined by mitotic count greater than 20 per 10 HPFs and/or Ki-67 index greater than 20%.

A highly significant correlation existed between the reported tumour grade and overall survival. Five-year survival rates for patients with low-grade, intermediate-grade and high-grade tumours were 87%, 38% and 0%, respectively. On assessment of the biopsies, mitotic rates and Ki-67 indices correlated strongly with overall survival. The authors conclude that a three-tiered grading classification for gastroenteropancreatic neuroendocrine tumours correlates with survival in the metastatic setting. Mitotic rates and Ki-67 indices are inversely associated with survival and can be analysed independently for assignment of grade.

Advances in Anatomic Pathology

September 2009

Vang R, Shih leM, Kurman RL. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol 2009;16:267–82.

This is an extensive review of grading of ovarian serous carcinomas based on a two-tier system: low and high grade, given they have different molecular pathways. Low-grade serous carcinomas have low-grade nuclei and infrequent mitoses, arise from adenofibromas or borderline tumours with slow, indolent step-wise progression to carcinomas, have frequent mutations of the KRAS, BRAF or ERBB2 genes, and lack TP53 mutations (Type I pathway). High-grade serous cancers have high-grade nuclei, easily found mitoses, and a proportion seem to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumours is rapid (Type II pathway). Most are characterised by TP53 mutations and lack mutations of KRAS, BRAF or ERBB2. Also demonstrated (and recently published, Am J Surg Pathol 2008;32:1800–6) is the low-grade serous carcinoma with an inverted micropapillary pattern (medium to large papillae, surrounded by a clear space with low-grade nuclei).

Bongiovanni M, Sadow PM, Faquin WC. Poorly differentiated thyroid carcinoma: a cytologic–histologic review. Adv Anat Pathol 2009;16:283–9.

The Turin histological criteria (2006) for poorly differentiated thyroid carcinoma are: trabecular/solid or insular pattern together with ONE of the following: convoluted nuclei, >3/10 mitoses per high-power field or necrosis. Immunohistochemically they are TTF-1 and thyroglobulin positive; molecularly, a subset are p53 positive, and ras mutations are the most common molecular alteration. These neoplasms require a combined aggressive treatment approach of surgery, I131 ablation and external beam radiotherapy.

Carmack SW, Lash RH, Gulizia JM, et al. Lymphocytic disorders of the gastrointestinal tract: a review for the practicing pathologist. Adv Anat Pathol 2009;16:290–306.

A most welcome and timely review on intraepithelial lymphocytes (IELs) in the gastrointestinal tract. ‘Lymphocytic oesophagitis’ (not fully characterised, has no association with Crohn disease, reflux, allergy, medications), lymphocytic gastritis (exclude Helicobacter pylori, coeliac sprue), autoimmune enteropathy (IELs: crypts>tips), coeliac disease (Marsh criteria/classification), colonic IELs (coeliac, autoimmune, drugs) and microscopic colitis (lymphocytic/collagenous colitis) are reviewed. My (KC) favourite comment at the end of the paper regarding IELs (paraphrased from a Rolls Royce salesman), ‘If you have to count, you can't diagnose it!’.

Houghton O, McCluggage WC. The expression and diagnostic utility of p63 in the female genital tract. Adv Anat Pathol 2009;16:316–21.

p63 Immunohistochemistry in the gynaecological tract highlights basal/reserve cells in the cervix (microglandular hyperplasia, basal/parabasal cells in cervical intraepithelial neoplasia (CIN) I, and mid-upper layers in CIN II–III), squamous cell carcinoma (negative in large cell neuroendocrine carcinoma) and is useful in separating placental site reaction/PSTT (p63 negative) from placental site nodule/epithelioid trophoblastic tumour (p63 positive).

Faragalla H, Weinreb I. Olfactory neuroblastoma: a review and update. Adv Anat Pathol 2009;16:322–31.

An excellent exposé on olfactory neuroblastoma with morphology and mimicks, immuno-histochemistry and differential diagnosis.

American Journal of Surgical Pathology

September 2009

Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumours presenting as omental masses-a clinicopathologic analysis of 95 cases. Am J Surg Pathol 2009;33:1267–75.

Omental gastrointestinal stromal tumours (GISTs) are clinicopathologically heterogeneous. Solitary tumours usually have gastric GIST-like morphology and a better prognosis than those with multiple tumours, which usually has small intestinal GIST-like histology. Omental GISTs unattached to the gastrointestinal tract often resemble gastric GISTs, suggesting that they may be gastric GISTs directly extending or parasitically attached into the omentum. Multiple omental GISTs more often resemble small intestinal GISTs, suggesting that they may be metastatic or detached from this source. KIT-positive Cajal cells were not found in normal omental tissues, failing to support the presence of these ancestral cells for GIST in the omentum.

Xu F, Xu J, Lou Z, et al. Micropapillary component in colorectal carcinoma is associated with lymph node metastasis in T1 and T2 stages and decreased survival time in TNM stages I and II. Am J Surg Pathol 2009;33:1287–92.

Colorectal carcinoma with a micropapillary pattern is an aggressive variant characterised by poorer differentiation, increased tumour budding, more frequent lymphovascular and perineural invasion, more frequent lymph node involvement, higher tumour, node, metastases (TMN) stage and less frequent β-catenin staining. A micropapillary pattern was found to be an independent adverse prognostic factor in a multivariate analysis.

Mosquera JM, Fletcher CDM. Expanding the spectrum of malignant progression in solitary fibrous tumours: a study of 8 cases with a discrete anaplastic component—is this dedifferentiated SFT? Am J Surg Pathol 2009;33:1314–21.

The spectrum of dedifferentiated soft tissue sarcomas (liposarcomas, chondrosarcoma, chordoma) has now been extended to include solitary fibrous tumours (SFTs). In SFTs, dedifferentiation is seen in large (>10 cm) deep-seated tumours showing an abrupt transition between the low-grade and high-grade areas with loss of CD34 immunostaining and increased p53 expression. These dedifferentiated SFTs have an increased recurrence/metastatic potential.

Weinreb I, Seethala RR, Hunt JL, et al. Intercalated duct lesions of salivary gland: a morphologic spectrum from hyperplasia to adenoma. Am J Surg Pathol 2009;33:1322–9.

Intercalated duct lesions of the salivary gland show a spectrum from hyperplasia to adenoma, with hybrid lesions associated with basal cell adenomas and epimyoepithelial carcinomas, lending credence to the intercalated ductular proliferations as putative precursor lesions.

Yamamoto H, Yamaguchi H, Aishima S, et al. Inflammatory myofibroblastic tumour versus igg4-related sclerosing disease and inflammatory pseudotumor: a comparative clinicopathologic study. Am J Surg Pathol 2009;33:1330–40.

This study compared 22 cases of inflammatory myofibroblastic tumours (IMTs) and 16 cases of IgG4-related sclerosing disease, including chronic sclerosing sialadenitis (n=8), mass-forming autoimmune pancreatitis (n=3), sclerosing cholangitis (n=1), retroperitoneal fibrosis (n=2), and chronic sclerosing dacryoadenitis (n=2). Obliterative phlebitis was seen in all sclerosing IgG4 lesions and only one IMT, and 68% of IMTs were anaplastic lymphoma kinase (ALK) positive, while all the IgG4-related sclerosing diseases were negative. The mean IgG4 plasma cell count in IMT was 6.4 per high-power field (HPF) with a IgG4:IgG ratio of 3.0%, while the IgG4 plasma cell count was 178.3 per HPF and IgG4/IgG ratio was 67.5% in IgG4-related sclerosing lesions.

Courville EL, Siegel CA, Vay T, et al. Isolated asymptomatic ileitis does not progress to overt Crohn disease on long-term follow-up despite features of chronicity in ileal biopsies. Am J Surg Pathol 2009;33:1341–7.

Isolated asymptomatic ileitis (active or chronic) detected on routine screening does not evolve into Crohn disease despite endoscopic/histologic overlap with the latter.

Nguyen T, Park JY, Scudiere JR, et al. Mycophenolic acid (cellcept and myofortic) induced injury of the upper GI tract. Am J Surg Pathol 2009;33:1355–63.

Mycophenolic acid (MPA) is an immunosuppressant drug commonly used in patients undergoing solid organ transplant. Its pattern of inducing injury in the colon is well known and features prominent crypt apoptosis that mimics graft-versus-host disease. Upper gastrointestinal effects have a wide array of symptoms: increased apoptotic counts, ballooning degeneration of parietal cells, chronic peptic duodenitis, active duodenitis, and coeliac-like features in the duodenum; chemical gastropathy, active chronic gastritis without Helicobacter pylori, and erosion in the stomach; reactive epithelial change, active oesophagitis, ulceration, and erosion in the oesophagus.

Montgomery E, Epstein JI. Anastomosing haemangioma of the genitourinary tract: a lesion mimicking angiosarcoma. Am J Surg Pathol 2009;33:1364–9.

Six cases of a rare vascular neoplasm mimicking angiosarcoma are presented. ‘Loosley’ lobulated lesions associated with a medium-calibre vessel composed of anatomosing capillary-sized vessels with scattered hobnail cells. Minimal stromal chronic inflammation made up of lymphocytes. Vascular fibrin thrombi with central sclerosis with focal necrosis are seen in the majority, some may have extramedullary haematopoiesis and hyaline globules like those seen in Kaposi sarcoma. No atypia, mitoses and multilayering. Lesion shows overlapping features of sinusoidal haemangioma and hobnail haemangioma.

Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumours: a study of 1840 cases. Am J Surg Pathol 2009;33:1401–8.

The overall sensitivity of DOG1 compares with KIT for the immunodetection of gastrointestinal stromal tumours (GIST) (1840 cases), highlighting spindle cells uniformly. DOG1 was slightly better for detection of gastric epithelioid tumours (including those with PDGFR mutations), while KIT was slightly more sensitive for small intestinal tumours. Both DOG1 and KIT combined was negative in 2.6% of GISTs.

Archives of Pathology and Laboratory Medicine

September 2009

Sarewitz SJ, Williams RB. Significant and unexpected versus critical results in surgical pathology. Arch Pathol Lab Med 2009;133:1366.

Nakhleh RE, Souers R, Brown RW. Significant and unexpected, and critical diagnoses in surgical pathology: a College of American Pathologists' survey of 1130 laboratories. Arch Pathol Lab Med 2009;133:1375–8.

A significant and important paper (with an accompanying editorial) from the CAP resource committee for quality expressing concern with the use of the term ‘critical value’ in reporting significant and unexpected results in surgical pathology, the main objection being that a surgical pathology report does not necessarily carry a numerical value (like clinical pathology). The recommended term is ‘critical results’ to report life-threatening findings to clinicians (eg, tumour causing superior vena caval obstruction, mucormycosis of nasal sinus, etc) with an immediate communication, as opposed to ‘significant and unexpected results’ requiring special attention being conveyed to the responsible clinician (with no immediate/imminent threat to life).

Turner MS, Goldsmith JD. Best practices in diagnostic immunohistochemistry: spindle cell neoplasms of the gastrointestinal tract. Arch Pathol Lab Med 2009;133:1370–4.

An excellent review of immunohistochemistry in this ‘Best practices in immunohistochemistry’ series: highlighting the role of different markers in the differential diagnosis of spindle cell neoplasms of the gastrointestinal tract.

Miranda RN, Lin L, Talwalkar SS, et al. Anaplastic large cell lymphoma involving the breast: a clinicopathologic study of 6 cases and review of the literature. Arch Pathol Lab Med 2009;133:1383–90.

Six cases of anaplastic large cell lymphoma of the breast.

Mohanty SK, Parwani AV. Mixed epithelial and stromal tumours of the kidney: an overview. Arch Pathol Lab Med 2009;133:1483–6.

A review of the long-awaited unifying concept/terminology of MEST (mixed epithelial and stromal tumour of the kidney). You will recall that several terms have been used in the past decade to describe these tumours. Essentially, they are biphasic epithelial-lined cysts with oestrogen receptor/progesterone receptor positive mesenchymal stroma reminiscent of ovarian stroma.


September 2009

Herrington CS. Recent advances in molecular gynaecological pathology. Histopathology 2009;55:243–9.

Another excellent short review of recent advances in gynaecological pathology outlining events in the last 5–10 years or so in the cervix, vulva, endometrium and ovary/tubes. A must read!

Chetty R, Serra S. Intraductal tubular adenoma (pyloric gland-type) of the pancreas: a reappraisal and possible relationship with gastric-type intraductal papillary mucinous neoplasm. Histopathology 2009;55:270–6.

Do intraductal tubular adenomas (ITAs) of the pancreas (pyloric gland type) share a possible pathogenetic link with intraductal papillary mucinous neoplasm? These authors think so, with their presentation of a small series along with literature suggesting that 50% of ITAs are associated with intraductal papillary mucinous neoplasm.

Modern Pathology

September 2009

Shaw PA, Rouzbahman M, Pizer ES, et al. Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers. Mod Pathol 2009;22:1133–8.

A large blinded review of patients (176) with BRCA mutations confirming that the putative cancer precursor is in the distal tubal mucosa. p53 signatures (in contrast) showed a similar frequency in both BRCA and control groups (25% each). Tubal intraepithelial carcinomas overexpress p53 protein more frequently in BRCA mutation carriers.

Tanas MR, Sthapanachai C, Nonaka D, et al. Pseudosarcomatous fibroblastic/myofibroblastic proliferation in perinephric adipose tissue adjacent to renal cell carcinoma: a lesion mimicking well-differentiated liposarcoma. Mod Pathol 2009;22:1196–200.

Pseudosarcomatous fibroblastic/myofibroblastic proliferation in perinephric adipose tissue adjacent to renal cell carcinomas may mimic well-differentiated liposarcoma. This was present in 20% of nephrectomy specimens in this study (12/59). Only 3/12 were associated with extrarenal renal cell carcinoma. The lesions comprised atypical stromal cells with myofibroblastic/fibroblastic proliferation. MDM2 (with fluorescence in situ hybridisation) was not amplified in the atypical stromal cells.

Sangoi AR, McKenney JK, Schwartz EJ, et al. Adenomatoid tumours of the female and male genital tracts: a clinicopathological and immunohistochemical study of 44 cases. Mod Pathol 2009;22:1228–35.

A review of adenomatoid tumours of the male and female genital tracts. Recent immunohistochemistry markers highlighting the mesothelial differentiation and morphological features (no lymphoid aggregates in women and well-circumscribed tumours in the fallopian tube) are presented.

Hameed O, Perry A, Banerjee R, et al. Papillary carcinoma of the breast lacks evidence of RET rearrangements despite morphological similarities to papillary thyroid carcinoma. Mod Pathol 2009;22:1236–42.

The recently described tall cell variant of papillary carcinoma in the breast is negative for RET rearrangements, despite the nuclear resemblance to papillary carcinoma of the thyroid.

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