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Lymphoreticular 119

Necrotising Histiocytic Lymphadenitis (Kikuchi-Fujimoto Disease)

Clin.: systemic Sx (NB: Kikuchi may be a forme fruste of SLE)

Cortical / paracortical foci of necrosis

Histiocytes of phagocytic (not epithelioid) type

PMN are absent

± Marked immunoblastic reaction

‘Banana’ nuclear fragments (apoptotic crescents)

d/dg non-reactive TB (do ZN and Wade-Fite for atypical mycobacteria)

d/dg lupus lymphadenitis (look for vasculitis, advise serology)

d/dg adult Still’s disease (also has follicular hyperplasia and paracortical T-cell reaction)

d/dg Yersinia/cat scratch (Bartonella [Rochalimaea] henselae)/LGV (Chlamydia trachomatis serotypes

L1, L2, L3): show serpiginous / bifurcating palisaded granulomas around central PMN / necrosis

d/dg tularaemia (Francisella tularensis): histologically like Yersinia, TB (or sarcoid)

d/dg Kawasaki’s disease: look for vasculitis, PMN and geographic (cf. focal) necrosis

HIV Lymphadenopathy

‘Explosive’ follicular hyperplasia with depleted mantles (‘naked follicles’)

Germinal centres may fuse to give irregular giant germinal centres

Mantle cells encroach into germinal centres → ‘folliculolysis’

Plasmacytosis, immunoblasts, vascularity of interfollicular areas

Monocytoid sinus B-cell reaction

Warthin-Finkeldey multinucleate FDC and IDC

Late changes: regression and disappearance of follicles, lymphocyte depletion, nodal ﬁbrosis

Assoc

changes: MAI, focal nodal KS, mycobacterial pseudotumour, etc.

Spindle Cell Tumours and Tumour-like Lesions in LN

Metastatic carcinoma (SCC, RCC, medullary thyroid, etc.)

Melanoma

Synovial sarcoma

Kaposi sarcoma

Mycobacterial pseudotumour

Palisaded myoﬁbroblastoma

Ectopic thymoma

Vascular transformation of LN sinuses (see p.319)

IDC tumour / sarcoma

FDC tumour / sarcoma

LAM (for details, see pp.92–93 )

Castleman’s Disease (Angiofollicular Lymph Node Hyperplasia)

Localised – hyaline vascular type

Large node (single rounded mass), local effects but no systemic Sx

Loss of sinus architecture

Large mantle zone of concentric (‘onion skin’) lymphocytes

Central regressed germinal centre with FDC and hyaline vessels

‘Lollipop’ sign of interfollicular vessel traversing to centre of follicle

Interfollicular zone contains lymphocytes, lots of vessels and few reactive cells (plasma cells, im-

munoblasts, eos.)

d/dg regressed follicle – lacks expanded onion skin mantle

d/dg Castleman-like reactive LN: common at some sites (e.g. mesenteric), does not form a large mass

and is probably of no clinical signiﬁcance

d/dg HL (because an occ. FDC may be pleomorphic simulating Hodgkin cells)

d/dg MCL

d/dg Castleman’s disease-like FCL

d/dg Castleman’s disease-like HIV lymphadenopathy:

 small / absent mantle

 more ﬂorid interfollicular plasmacytosis

 less vascular interfollicular zone

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Lymphoreticular 120

 preserved sinus architecture

 other features of HIV LNp / infection / focal KS

Localised – plasma cell type

Matted group of large nodes, systemic Sx

Obliteration of sinuses

Follicular hyperplasia ± scattered regressed follicles (hyaline vascular follicles are rare)

Mantle zone surrounded by sheets of plasma cells (polyclonal or monotypic)

Diagnosis of exclusion: d/dg: CTD (e.g. RhA), syphilis, HL, plasmacytoma, HIV

Systemic (multicentric) type

Rare, multiple peripheral LN / systemic (liver, kidney, skin, bone marrow, CNS, etc.)

Preserved sinuses with ‘inspissated’ lymph

Mixture of regressed and hyperplastic follicles ± hyaline vascular follicles

Perifollicular sheets of plasma cells

HHV8 +ve plasmablasts in the mantle zone (may form aggregates of microlymphoma)

± Interfollicular vascular proliferation

Associations: HHV8 (even if HIV −ve), KS / plasmablastic lymphoma, osteosclerotic myeloma (Crow-

Fukase POEMS syndrome), other neoplasms (e.g. chordoid meningioma)

d/dg: exclude Castleman-like lymphomas, HIV, CTD, nodal KS, HL

Dermatopathic Lymphadenopathy

Skin lesions may or may not be present

Mottled expansion of the paracortex by histiocytes, plasma cells, immunoblasts ± Cc-like cells

Pigment (melanin / haemosiderin) may be sparse to abundant ± cholesterol

Langerhans cells and eosinophils are usu. present in the inﬁltrate

d/dg HX, HL, monocytoid leukaemia

d/dg nodal involvement by MF (this requires partial effacement of architecture by MF cells)

EBV Lymphadenopathy (Infectious Mononucleosis)

Florid paracortical angioimmunoblastic reaction ± sheets of immunoblasts

Sinus B-cell reaction with transformed cells

Destruction of B-cell areas (esp. in advanced cases, this mimics loss of architecture)

Mitoses ++

Bi-/multi-nucleated immunoblasts (nucleoli usu. smaller and more haematoxyphilic cf. H/RS cells)

Immuno: immunoblasts show CD20, CD30 (Ki-1), CD43, LMP +ve

d/dg lymphoma (esp. ALCL / HL) but preserved architecture, characteristic IM clinical, serology and

PB atypical T-cells and –vity for ALK all help

Eosinophil Granuloma (HX)

Langerhans cell inﬁltrate is sinus-centric cf. paracorticocentric as in dermatopathic LNp

See also: pp.57–58, p.94 and p.333.

Follicular Dendritic Cell Sarcoma (= Dendritic Reticulum Cell Sarcoma, FDC Sarcoma)

Clin.: usu. one nodal site, may locally recur but mets / death are rare

Arch: storiform, fascicles, sheets, meningothelioid whorls (± nuclear pseudoinclusions), ± cysts

Cytology: spindle cells with bland, oval, vesicular nuclei

Other: sharp demarcation from uninvolved areas, intratumoural and perivascular lymphocytes (B and

T) ± follicles

Immuno: +ve for EMA, CD21,23,35; ±ve for S100, MSA, CD20,45,68; −ve for CD1a,3,34,79a, CK,

desmin, HMB45

EM: desmosomes are present (unlike d/dg IDC sarcoma) but no Birbeck granules or melanosomes

d/dg: see list in ‘Spindle Cell Tumours in LN’ section; also inﬂammatory myoﬁbroblastic tumour /

inﬂammatory pseudotumour (esp. if extranodal)

Interdigitating Dendritic Cell Sarcoma (= Interdigitating Reticulum Cell Sarcoma, IDC Sarcoma)

Clin.: usu. one nodal site initially ± B symptoms; mets / death are common (upto 50% of cases)

Arch: tumour is centred in the paracortex (if LN is not completely replaced), necrosis is usu. absent

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Lymphoreticular 121

Cytology: spindle cells with spindle to round / convoluted nuclei of variable grade; epithelioid cells

with ill-deﬁned cytoplasm (may be pleomorphic); sheets of round cells may also be seen

Other: intratumoural T-cells (hardly any B-cells)

Immuno: +ve for S100, vimentin; ±ve for CD45,68; −ve for EMA, CD1a, 3, 20, 21, 25, 30, 34, 35,79a,

CK (see also p.109)

EM: desmosomes are absent (unlike d/dg FDC sarcoma) and no Birbeck granules or melanosomes

d/dg: see list under ‘Spindle Cell Tumours in LN’, above; also histiocytoses / histiocytic sarcoma,

ALCL

The Spleen

Normal (see Fig. 10.1)

Capsule and septa, white pulp (PALS and follicles) and red pulp (cords of Billroth and sinusoids)

Marginal zone (MZ) is for carbohydrate responses (e.g. pneumococcal vaccine / HS)

PALS (T4)

cord

sinusoid

WHITE PULP (low power)

RED PULP (high power)

Perifollicular

capillary network

Littoral endothelial

cells (CD8 +ve)

Central artery / arteriole

FIGURE 10.1 Normal spleen

Causes of a Small Spleen

Old age

Intestinal malabsorption e.g. coeliac disease

Sickle cell anaemia

HIV

Congenital hypoplasia

Trauma

↑ White pulp

↑ Prominence of perifollicular capillary network (= ‘perifollicular ﬂare’)

Reactive Patterns

White pulp:

 germinal centre formation

 ↑ MZ ± perifollicular ﬂare (seen esp. in post vaccination [pneumococcal] spleen)

 ↑ PALS (incl. more blasts)

Red pulp: congestion, plasmacytosis, T8 lymphocytosis, cord ﬁbrosis

SLE

Periarteriolar concentric ﬁbrosis (also occurs in sarcoidosis)

Plasmacytosis

Reactive white pulp (vide supra)

analogous to LN paracortical reaction and seen esp. with viral infections / ITP

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Lymphoreticular 122

Red Cell and Platelet Sequestration Disorders

In Table 10.3 ↑ indicates reactive hyperplasia and ↓ represents atrophy.

TABLE 10.3 Differential features in sequestrations

Red Pulp White Pulp

HS RBC loose in cords & empty sinusoids ↑(esp. MZ)

ITP platelets in cord M (‘Gaucher-like’) ↑/↓ (± NHL)

AIHA RBC in sinus M ↑/↓ (± NHL)

Sickle Cell Disease

Early: drepanocyte (sickle cell) expansion of the cords with sinus compression

Later: multiple infarcts

Later: siderotic calciﬁc ﬁbrous foci (Gamna-Gandy bodies

) – which may contain vessels and in which

some of the encrusted collagen ﬁbres have a hyaline greenish appearance and may branch

Eventually: spleen replaced by a small siderotic ﬁbrous nodule (‘autosplenectomy’)

EBV Spleen (Infectious Mononucleosis)

Florid CD30+ve immunoblastic reaction in red pulp

Inﬁltration of trabecular vein intima by immunoblasts

± Haemophagocytosis (histiocytes ++)

± Granulomas (may be necrotising)

d/dg leukaemia / ALCL: use CPC; EBV shows mixed T + B-cell immuno and lacks a macro tumour

HIV

Early: splenomegaly

Secondary: infection / KS / lymphoma / ITP-like pattern but with ↑T8 cells

Late: atrophy

Granulomatous Splenitis

Infective:

 miliary TB, EBV, syphilis, Brucella, toxoplasmosis (white pulp features similar to LN)

 histoplasmosis (granulomas aggregate, encapsulate and ultimately calcify); ‘infantile’ form

shows diffuse red pulp histiocytosis with parasitised M – d/dg leishmaniasis

Paraneoplastic: (e.g. accompanying lymphoma – does not imply lymphoma in spleen)

Other: sarcoidosis (± onion skin periarteriolar ﬁbrosis), lipogranulomas, foreign body, granulomatous

vasculitides (e.g. WG)

Histiocytic and Histiocytoid Inﬁltrates

ITP (q.v.)

Histiocyte-rich B-cell lymphoma

Haemophagocytic syndromes (incl. T-cell lymphomas, viral infection and MDS)

Granulomatous splenitis (vide supra)

‘Infantile’ form of histoplasmosis (disseminated red pulp parasitised M) d/dg leishmaniasis

Visceral leishmaniasis (also get plasmacytosis) d/dg infantile histoplasmosis

Malaria (slate colour macro; red pulp M with pigment)

Lipidoses (e.g. hypertriglyceridaemia / cholesterolaemia which may be 2

◦

e.g. to DM) and storage

diseases e.g. Gaucher’s disease (q.v.)

HX (q.v.) – the Hand-Sch¨uller-Christian variant has lipidised M

FDC sarcoma and true histiocyte neoplasms (very rare)

Systemic Mastocytosis

Red pulp mast cells with tendency to aggregate

Paratrabecular / subcapsular predilection

Assoc

ﬁbrosis

d/dg HCL but HCL is diffuse and has different immuno (for more detail, see Chapter 9: Bone Marrow)

also seen in other conditions e.g. congestion 2

◦

to portal HT and may be the result of intrafollicular haemorrhage

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Lymphoreticular 123

Gaucher’s Disease (Gaucher-Schlagenhaufer Cerebroside Kerasinosis)

Autosomal recessive defect of glucocerebrosidase −→ accumulation of ‘Gaucher cells’:

 bloated M with small eccentric nucleus and abundant ‘tissue paper’ cytoplasmic folds

 DPAS +ve, TRAP +ve

Spleen: stuffed cords with sparing of white pulp (unlike d/dg malignancy) ± infarcts

Liver: stuffed sinusoids ± portal tract aggregates

Bone marrow: interstitial aggregates

LN: paracortical aggregates

Other: fever, anaemia, skin pigmentation, ocular conjunctival melanosis and pingueculae

MDS

Erythrophagocytosis

Plasmacytosis

EMH

± CMML inﬁltration of red pulp

± Transformation foci (of AML blasts)

Extramedullary Haemopoiesis (EMH )

Physiological EMH:  small foci

 megakaryocytes normal (not clustered)

 other organs have similar foci

Pathological EMH:  peliosis

 megakaryocytes large, hyperlobated and clustered

 occurs in chronic myeloproliferative diseases (as a form of metastasis)

CML

Diffuse inﬁltration of red pulp (cords and sinuses)

Over-running and obliteration of white pulp

Myeloid cells maturing to granulocytes

MPO and CAE +ve

d/dg granulocytic hyperplasia 2

◦

to G-CSF Rx (e.g. ﬁlgrastim or lenograstim)

Myeloﬁbrosis

A cause of massive splenomegaly (upto 7Kg)

Red pulp expansion by pathological EMH ++ with small dysplastic megas (± large clusters)

White pulp atrophy

Infarcts common

± Capsular +/ red pulp ﬁbrosis

Features of pre-existing MPD (e.g. PRV / CML / ET)

Hairy Cell Leukaemia (HCL)

Weight may range from upper end of normal to ≥1-2Kg

Diffuse inﬁltration of red pulp (evenly spaced-out cells without prominent nucleoli)

Limited white pulp involvement / atrophy

Paracortical involvement of LNs and sinusoidal involvement of liver (see p.105 for bone marrow)

d/dg splenic MZL (but MZL has a nodular inﬁltrate in bone marrow)

d/dg B-prolymphocytic leukaemia

d/dg mastocytosis but HCL is diffuse, lacks mast cell-assoc

ﬁbrosis and has different immuno

Immuno / other features: see p.105

Lymphomas

Macro:

General: Splenic size is not important. Sample any hilar LN

Speciﬁc:  low grade B-cell: FCL, MCL, MZL →miliary nodularity (also seen in reactive)

 high grade B-cell: large white nodules

 HL: discrete nodules

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Lymphoreticular 124

Micro:

General: most low grade lymphomas have a ‘follicular’ pattern – not just FCL

Speciﬁc:  FCL: Cb and Cc, no red pulp extension

 MCL: monotonous, Cc-like

cells and red pulp satellite nodules

 MZL:  ↑ MZ (immunoblastoid) → ‘reversal of follicles’

 satellite nodules in the red pulp

 granulomas, ± circulating villous lymphocytes (SLVL)

 CLL:  para-immunoblasts and proliferation centres

 involves white pulp and extends into the red ± invades vessel walls

 ± plasmacytoid cells (also seen in LPL)

 Hepatosplenic  TCL: An aggressive lymphoma of young adults (M>F); no

peripheral LNp; diffuse red pulp involvement and sparing / atrophy of the white

pulp. CD3, TIA-1 and TCR1 +ve, CD56 ±ve, rearranged TCR, [i(7q)] +ve

Immuno:

For speciﬁc conditions see previous sections in this chapter and see Chapter 9: Bone Marrow

CD21 for FDC, shows:  expansion of germinal centres by FCL

 colonisation of germinal centres by MZL

 destruction of germinal centres by MCL.

Bibliography

Anagnostou, D. (2005) Pitfalls in the pattern of bone marrow infiltration in lymphoproliferative disorders. Current Diagnostic Pathology, 11 (3),

170–179.

Arno, J. (1980) Atlas of Lymph Node Pathology,1

edn, MTP Press Ltd, Lancaster.

Bain, B.J., Clark, D.M., Lampert, I.A. and Wilkins, B.S. (2001) Bone Marrow Pathology,3

edn, Blackwell Science Ltd, Oxford.

Bacon, C.M., Du, M-Q. and Dogan, A. (2007) Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists. Journal of

Clinical Pathology, 60 (4), 361–372.

Cerroni, L. (2006) Lymphoproliferative lesions of the skin. Journal of Clinical Pathology, 59 (8), 813–826.

Cerroni, L. and Kerl, H. (2001) The clinicopathological spectrum of cutaneous B-cell lymphomas, in Progress in Pathology, vol. 5 (eds N. Kirkham

and N.R. Lemoine), Greenwich Medical Media Ltd, London, pp. 1–16.

Chan, J.K.C., Banks, P.M., Cleary, M.L. et al. (1994) A proposal for classification of lymphoid neoplasms (by the International Lymphoma Study

Group) Histopathology, 25 (6), 512–536.

Cochran, A.J. (2001) Sentinel node pathology, in Progress in Pathology, vol. 5 (eds N. Kirkham and N.R. Lemoine), Greenwich Medical Media Ltd,

London, pp. 45–56.

Cotran, R.S., Kumar, V. and Collins, T. (eds) (1999) Robbins Pathologic Basis of Disease,6

edn, W.B. Saunders Co., Philadelphia.

Cserni, G. (2003) Nodal staging of colorectal carcinomas and sentinel nodes. Journal Clinical Pathology, 56 (5), 327–335.

Cserni, G., Bianchi, S., Vezzosi, V. et al. (2006) The role of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in

patients with lobular breast carcinoma. Journal of Clinical Pathology, 59 (5), 518–522.

Dong, H.Y. (2003) B-cell lymphomas with coexpression of CD5 and CD10. American Journal of Clinical Pathology, 119 (2), 218–230.

Dupin, D., Diss, T.L., Kellam, P. et al. (2000) HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive

plasmablastic lymphoma. Blood, 95 (4), 1406–1412.

Franco, R., Camacho, F.I., Caleo, A. et al. (2006) Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter

failure-free survival. Modern Pathology, 19 (8),1055–1067.

Goodlad, J.R. and Hollowood, K. (2001) Primary cutaneous B-cell lymphoma. Current Diagnostic Pathology, 7 (1), 33–44.

Isaacson, P.G. and Norton, A.J. (eds) (1994) Extranodal Lymphomas,1

edn, Churchill Livingstone, London.

Jaffe, E.S., Harris, N.L., Diebold, J. and M¨uller-Hermelink, H-K. (1994) World Health Organisation classification of neoplastic diseases of the

hematopoietic and lymphoid tissues – a progress report. American Journal of Clinical Pathology, 111 (Suppl.1), S8–S12.

Jaffe,E.S., Harris, N.L., Stein,H. and Vardiman, J.W.(eds) (2001) WHO Classificationof Tumours: Pathology &Genetics Tumours of Haematopoietic

and Lymphoid Tissue,1

edn, IARC Press, Lyon.

Jensen, K.C., Higgins, K.P.T., Montgomery, K. et al. (2007). The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant

neoplasms. Modern Pathology 20 (8), 871–877.

Junqueira, L.C., Carneiro, J. and Long, J.A. (1986) Basic Histology.5

edn, Appleton-Century-Crofts (Prentice-Hall), Norwalk, CT.

Kaifi, J.T., Strelow, A., Schurr, P.G et al. (2006) L1 (CD171) is highly expressed in gastrointestinal stromal tumors. Modern Pathology, 19 (3),

399–406.

Lee, F.D. (1994) Unusual sites and types of lymphoma, in Recent Advances in Histopathology, vol. 16 (eds P.P. Anthony, R.N.M. MacSween and

D.G. Lowe), Churchill Livingstone, Edinburgh, pp. 73–93.

Lin, P., Mahdavy, M., Zhan, F. et al. (2004) Expression of PAX5 in CD20-positive multiple myeloma assessed by immunohistochemistry and

oligonucleotide microarray. Modern Pathology, 17 (10), 1217–1222.

Liu, Z., Dong, H.Y., Gorczyca, W. et al. (2002) CD5-Mantle cell lymphoma. American Journal Clinical Pathology, 118 (2), 216–214.

here Cc-like just means ‘like centrocytes’ and does not imply the Cc-like cells of MALToma / MZL

JWBK208-10 December 8, 2007 16:2 Char Count= 0

Lymphoreticular 125

MacLennan, K.A, and Diebold, J. (1998) Anaplastic large cell lymphoma. Current Diagnostic Pathology, 5 (4), 165–173.

McKenney, J.K., Weiss, S.W. and Folpe, A.L. (2001) CD31 Expression in Intratumoral Macrophages: a potential diagnostic pitfall. American Journal

of Surgical Pathology, 25 (9), 1167–1173.

Merzianu, M., Jiang, L., Lin, P., et al. (2006) Nuclear BCL-10 expression is common in lymphoplasmacytic lymphoma/Waldenstr¨om macroglobuli-

naemia and does not correlate with p65 NF-κB activation. Modern Pathology, 19 (7), 891–898.

Murray, C.A., Leong, W.L., McCready, D.R. and Ghazarian, D.M. (2004) Histopathological patterns of melanoma metastasis in sentinel lymph

nodes. Journal of Clinical Pathology, 57 (1), 64–57.

Robb-Smith, A.H.T. and Taylor, C.R. (1981) Lymph Node Biopsy: A Diagnostic Atlas,1

edn, Miller Heyden Ltd, London.

Schraders, M., de Jong, D., Kluin, P. et al. (2005) Lack of Bcl-2 expression in follicular lymphoma may be caused by mutations in the BCL2 gene

or by absence of the t(14;18) translocation. Journal of Pathology, 205 (3), 329–335.

Smellie, W.S.A., Forth, J., Smart, S.R.S. et al. (2007) Best practice in primary care pathology: review 7. Journal of Clinical Pathology, 60 (5),

458–465.

Slater, D.N. (2003) Diagnosis and classification of cutaneous lymphoproliferative disease, in Recent Advances in Histopathology, vol. 20 (eds

D.Lowe and J.C.E. Underwood), Royal Society of Medicine Press Ltd, London, pp. 53–72.

Simpson, R.H.W. and Sarsfield, P.T.L. (1997) Benign and malignant lymphoid lesions of the salivary glands. Current Diagnostic Pathology, 4 (2),

91–99.

Stansfeld, A.G. and d’Ardenne, A.J. (eds) (1992) Lymph Node Biopsy Interpretation,2

edn, Churchill Livingstone, London.

Stevenson, F.K. and Wright, D.H. (1998) Hodgkin’s disease and immunoglobulin genetics, in Progress in Pathology, vol. 4 (eds. N. Kirkham and

N.R Lemoine), Churchill Livingstone, Edinburgh, pp. 99–111.

Swerdlow, S.H. (1997) Post-transplant lymphoproliferative disorders: a working classification. Current Diagnostic Pathology, 4 (1), 28–35.

Symmers, W. St. C. (ed) (1976) Systemic Pathology. vol. 2, 2

edn, Churchill Livingstone, London.

Taylor, C. and Cote, R.J. (2006) Immunomicroscopy. A Diagnostic Tool for the Surgical Pathologist., 3

edn, Saunders Elsevier, London.

Warnke, R.A., Weiss, L.M., Chan, J.K.C., Cleary, M.L. and Dorfman, R.F. (1995) Tumors of the lymph nodes and spleen, fascicle 14 in Atlas of

Tumor Pathology 3

series, AFIP, Washington D.C.

Wheater, P.R., Burkitt, H.G. and Daniels, V.G. (1987) Functional Histology: A text and colour atlas,2

ed., Churchill Livingstone, Edinburgh.

Wilkins, B.S. (1997) Simplifying the spleen: a new look at splenic pathology, in Progress in Pathology, vol. 3 (eds N. Kirkham, N.R. Lemoine),

Churchill Livingstone, NY, pp. 211–231.

Ye, H., Gong, L., Liu, H. et al. (2005) MALT lymphoma with t(14;18)(q32;q31)/IGH-MALT1 is characterised by strong cytoplasmic MALT1 and

BCL10 expression. Journal of Pathology, 205 (3), 293–301.

Web sites

Royal College of Pathologists (2002) Standards and minimum datasets for reporting cancers: Minimum dataset for the histopathological reporting

of lymphoma. Available online at: www.rcpath.org.uk (accessed May 2005).

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Alimentary Tract 126

11. Alimentary Tract

Normal

Mucins

Gastric: neutral mucin (± acid mucin in some foveolar cells but not in goblet form)

Small intestinal goblets: both neutral and acid mucin (sialomucin i.e. carboxylated)

Colonic goblets: both neutral and acid mucin (sulphomucin i.e. sulphated)

Oesophagus

l.p. papillae should rise to ≤1/2 the squamous epithelial thickness

Basal layer is usu. <3 cells thick or 15% of the squamous epithelial thickness

IELs: an occasional squiggle cell is normal (T8)

Stomach

Lymphoid tissue:  superﬁcial l.p. should have none or only an occ. lymphocyte +/ plasma cell

 deep l.p. should have no diffuse lymphocytes or plasma cells

 an occ. 1

◦

lymphoid aggregate may be seen just superﬁcial to the m.m.

 IELs (T8): <25/100 epithelial cells, and usu. <3/100

Cardiac mucosa:  spaced-out and irregularly distributed mucinous glands (simple & compound)

with foamy mucin (Brunner’s gland-like) and some cystically dilated

 smooth muscle slips may rise to separate glandular lobules

 light lymphoplasmacytic inﬁltrate is probably normal

 ± some oxyntic (parietal / acid-producing) cells

Pyloric mucosa: glands gradually change to duodenal type .

. do not diagnose intestinal metaplasia here

Duodenum

Lymphoid tissue:  l.p.: many lymphocytes, IgA plasma cells, few eos; mast cells (<8 per hpf); no

PMN

 l.p. lymphocyte gradient: most are in the deeper l.p. & fewest at villus tip

 2

◦

follicles are normal and more numerous in the distal SI

 IELs (T8): <20 per 100 epithelial cells (gradient: fewest at villus tip)

Villus height is ≥ 2 × crypt length (and often 3 × to 5 ×) away from Brunner’s / lymphoid follicles

Vertical smooth muscle slips extend up into normal villi

Pseudomelanosis duodeni: iron-containing pigment in l.p. M

Colon

l.p. lymphoplasmacytic gradient: the inﬁltrate is most intense superﬁcially and least deep

Caecal and right colon may have some plasma cells in the deepest l.p. at the crypt bases

More distal colon should have no plasma cells at crypt base

‘Herniation’ of crypts into superﬁcial submucosal lymphoid follicles may occur (lymphoglandular

complex)

Paneth cell gradient: most in caecum and decrease to zero by the mid-right colon

Endocrine cells: most in rectum, decreasing to transverse; second peak in caecum, decreasing to trans-

verse

IELs (T8): <20 per 100 epithelial cells – in fact, ‘normal’ colon averages 4 per 100

Erosion, Ulceration and Aphthae

Loss of surface epithelium may be artefactual .

. need evidence of pathology (e.g. ﬁbrin)

Erosion is ulceration that does not extend beyond the lamina muscularis mucosae

Ulcers involve the full-thickness of the mucosa and extend (at least) into the submucosa

the one exception being the cardia where a light inﬁltrate is considered normal

Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum. Paul J. Tadrous



2007 by John Wiley & Sons, Ltd. ISBN: 978-0-470-51903-5

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Alimentary Tract 127

Aphthae are a clinical diagnosis in which histology usu. shows a circumscribed superﬁcial erosion with

a mixed chronic inﬂam

inﬁltrate at the base and may overlie mucosal lymphoid aggregates. In the

colon in Crohn’s they have a characteristic structure that may help in diagnosis (vide infra)

Grading (General Criteria for Alimentary Tract Carcinomas)

This general ‘system’ from the UICC applies to many carcinomas (not just GI) as part of TNM6 but

see speciﬁc tumour types for detailed guidance and variant methods

Applies to: oesophagus, upper & lower GI, anus, pancreas, gallbladder, extrahepatic biliary tree

GX: grade cannot be assessed

G1-4: well diff, moderately well diff, poorly diff, undifferentiated

Dysplasia (General Criteria for Glandular Dysplasia) and Carcinoma

Criteria are modiﬁed depending on site and circumstance (see speciﬁc examples e.g. DALM in UC)

Cytological:  nuclear enlargement, hyperchromasia, pleomorphism, stratiﬁcation

 mitotic activity (increased, abnormal, beyond usual proliferative compartment)

Architectural  gland crowding, branching, budding, cribriformity, papillarity, surface villosity

 lack of maturation (abnormalities continue to the surface)

 abrupt transition to non-neoplastic glands

Vienna classiﬁcation of GI neoplasia (an attempt to unify Western and Japanese reporting):

Category 1: negative for dysplasia

Category 2: indeﬁnite for dysplasia (see ‘Oesophagus’ pp. 135–136 and ‘Flat Dysplasia in Chronic

idiopathic Inﬂammatory Bowel Disease (CIBD)’, p. 150)

Category 3: non-invasive low grade neoplasia (= low grade dysplasia / adenoma)

Category 4: non-invasive high grade neoplasia

4.1: high grade dysplasia / adenoma

4.2: non-invasive carcinoma (= CIS)

4.3: suspicion of invasion (incl. suspicion of invasion into the l.p.)

Category 5: invasive carcinoma (see criteria below)

5.1: intramucosal (incl. l.p./m.m.): l.p. invasion is insufﬁcient for colorectal

CA in the UK

5.2: submucosal and beyond: this required for a diagnosis of colorectal

CA in the UK

Carcinoma:  cribriform formations (a criterion accepted by some Eastern pathologists)

 solid cell islands at least one of these (together with

 single cell invasion



dysplastic glands) is required by

 desmoplastic reaction most Western pathologists

 NB: desmoplasia is not always seen in early invasion and atypical architectures (e.g.

cribriform) are more suggestive of invasion if expansile and disrupting other normal structures

d/dg Isaacson lesions (reactive changes seen beneath ulcers):

Type I (epithelial): crowded acini with cytological atypia in a ﬁbrinoid matrix: mitoses are scant / absent

and the acini merge with benign reactive glands at the periphery

Type II (stromal): spindle / bizarre cells ±macronucleoli, cytoplasmmayshow granularity: homogenous

chromatin, mitoses scant / absent. Many of these are endothelial.

d/dg chemoRx/radioRx atypia: see ‘Dysplasia (Flat / Non-Polypoid)’ on p. 138 and see p. 148.

Mouth and Oropharynx

Classiﬁcation of Odontogenic / Facial Cysts

A) Developmental

◦

dentigerous cyst

◦

odontogenic keratocyst (may be a benign neoplasm cf. developmental)

B) Inﬂammatory

◦

radicular cyst both arise from a

◦

paradental cyst



periapical granuloma

villosity is also seen in normal small bowel mucosa / metaplasia & UC inﬂammation without dysplasia

JWBK208-11 December 8, 2007 16:3 Char Count= 0

Alimentary Tract 128

Dentigerous Cyst

Assoc

with an unerupted tooth (usu. 3rd molar ‘wisdom’ in adults / canine in a child)

Can be very large; cyst is attached to the crown of the tooth

Cyst envelops the crown of the tooth .

. important to check X-ray

Inﬂammation only in traumatised areas – otherwise uninﬂammatory

Thin and regular squamous lining (gets thicker with age)

Focal keratinisation in 10% of cases

Odontogenic Keratocyst

Large soap bubble scalloped lucency which erodes bone but

spares nerve

If multiple consider Gorlin-Goltz (basal cell naevus)syndrome

Inﬂammation only in traumatised areas – otherwise uninﬂam-

matory

Cyst has hairpin bends and ‘satellite cysts’ (see Figure 11.1)

Main cyst lumen

FIGURE 11.1 Odontogenic keratocyst

Prominent basal layer with reversed polarity (d/dg cystic ameloblastoma)

Thin squamous lining (8–12 cell layers) with corrugated surface and without rete pegs

Most (85%) are parakeratotic but some (15%) are orthokeratotic

Progresses, recurs and enlarges .

. → radical surgery with jaw prosthesis

Radicular (Dental) Cyst

Assoc

with a carous non-vital tooth (or PMHx thereof) – this is necessary for diagnosis

Stratiﬁed squamous epithelium

Epithelium has an arcade-like / reticular conﬁguration at ﬁrst (becomes attenuated with age)

Inﬂammation (in wall) and cholesterol clefts (in wall and contents) ± foam cells

Mucinous metaplasia (40%, ± respiratory epithelium in maxillary cysts)

Hyaline laminated crescents (Rushton bodies – only seen in 5% but speciﬁc) ± PMN

Apical Granuloma

This is a sequel to pulpitis in a carous tooth; may progress to form a radicular cyst

Chronic inﬂammatory granulation tissue

Squamous epithelium (as nests or a lacy network) permeates the lesion

Paradental Cyst

Similar to apical granuloma but assoc

with a partially impacted 3rd molar (‘wisdom’ tooth)

Ameloblastoma

Adults, uni/multicystic (‘soap bubble’ lucency on X-ray)

Biphasic:

◦

palisaded columnar / cuboidal epithelium with reversed polarity

◦

stellate reticulum

No hard tissue formed except in some desmoplastic types that can have bone (if hard tissues are present

consider d/dg craniopharyngioma)

The stellate reticulum may show squamoid (± keratin) +/ granular cell change

Epithelium may show focal squamous metaplasia in cystic areas

Bland cytology and no mitoses (if more than a few mitoses consider malignant ameloblastoma)

Variants: follicular, plexiform (interconnecting strands), desmoplastic, papilliferous and basaloid

d/dg ameloblastic hyperplasia in the wall of a dentigerous cyst

Malignant change:  mitoses

 clear cell areas (=low grade malignancy if otherwise benign ameloblastoma)

 cytological atypia and cell crowding ± necrosis

 NOT invasive margins (non-metastasising tumours may show invasion)

Ameloblastic Fibroma

Child / adolescent

Branching mushrooms of ameloblastoma-like epithelium in loose cellular ﬁbrous stroma

Cell-free zone in stroma around epithelium

Mitoses uncommon