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Endocrine 279

Exclude metastatic carcinoma/granular cell tumour and consider a glial, meningeal or neural lesion

(! remember the normal neurohypophysis)/hypophysitis ± granulomas/Rathke’s pouch/cleft lesions

Carcinoid Tumours

See other chapters (e.g. pp. 93–94, pp. 139–140, p. 152 and pp. 252–253) for deﬁnitions of special

types of carcinoid. For endocrine pancreas, see pp. 178–179.

Grading :

1. ≈ usual-type carcinoid

a. small nests/trabeculae, palisaded round cells, uniform nuclei with ≈ absent nucleoli and no

mitoses

b. signiﬁcant solid areas, non-aligned cells ± spindle forms, anisonucleosis, visible nucleoli and

mitoses sparse but normal

2. ≈ atypical carcinoid See pp. 93–94 and pp. 139–140.

3. ≈ malignant carcinoid NB: avoid the term ‘malignant carcinoid’



because all grades may be malignant

Features correlated with aggressive behaviour in general (speciﬁc tumours may have other features):

 higher grade (incl. nuclear grade e.g. prominent nucleoli) and local invasiveness

 large size

 coagulative tumour cell necrosis

 vascular invasion

 ↑ proliferation (mitotic count and Ki-67 LI)

Paraganglioma

Arch.: zellballen (+/ trabeculae in abdominal ones) surrounded by retic (but individual cells are not)

The cell balls are surrounded by ﬁne capillaries ± stromal haemorrhage/hyaline

Cells have moderate cytoplasm (± eosinophilic globules in abdominal paragangliomas)

Nuclei may show eosinophilic pseudoinclusions, ‘endocrine-type’ atypia and more irregular/vesicular

chromatin ± distinct nucleoli (cf. d/dg carcinoids)

Abdominal paragangliomas may look like phaeochromocytoma (p. 276)

Gangliocytic paraganglioma: see p. 179

Chemodectomas are paragangliomas of carotid, aortic, Zukerkandl and jugulotympanic bodies

Immuno: CgA (± other NE Ags) +ve, CK and SMA −ve, sustentacular cell +vity for S100 or

GFAP

Malignancy: ? few/no sustentacular cells, ? mets/vasc. invas

, ? necrosis/mitoses: none are deﬁnite

d/dg MTC, myxopapillary ependymoma, paraganglioid carcinoid, PLAT, melanoma, laryngeal NEC:

presence of sustentacular cells and absence of CK favour paraganglioma

d/dg glomus tumour

: SMA −ve, CgA +ve, sustentacular cell +ve, rich stromal microvasculature

and lack of pericellular reticulin all favour paraganglioma

d/dg glomus coccygeum: this is a normal structure (see p. 286 under the d/dg of ‘Glomus Tumour’)

Familial/Multiple Endocrine Pathology Syndromes

Multiple Endocrine Adenopathy/Neoplasia (MEA/MEN)

Most are AD but some (esp. MEN 2b) arise as spontaneous mutations with no FHx

MEN 1: (Wermer, all the ‘P’s) – parathyroid, pancreaticoduodenal (PP, ZE, etc.), pituitary (PRL, etc.),

± adrenocortical proliferations

MEN 2: MTC and phaeochromocytoma and

a) parathyroid (Sipple)

b) mucosal neuromas and GIT ganglioneuromas (MTC is aggressive; also called MEN 3)

NB: some normal paraganglia are termed glomi (e.g. glomus jugulare, glomus caroticum, etc.) and their cells are called glomus

type 1 (=chief) and 2 (= sustentacular) cells. This has resulted in some of their paragangliomas also bearing the term ‘glomus’ e.g.

‘glomus jugulare tumour’. All this can cause terminological confusion with true glomus tumours (which are not paragangliomas) –

see p. 285

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Endocrine 280

Familial MTC

Does not have the other features of MEN

Not to be confused with Carney triad:

◦

epithelioid GIST

◦

pulmonary chondroma

◦

non-adrenal paraganglioma

Carney Complex / Syndrome

Myxomas (skin and heart)

Lentigines (skin)

Melanotic Schwannomas

Adrenal, pituitary and thyroid neoplasms and Sertoli cell tumours

Bibliography

Al-Brahim, N.Y.Y. and Asa, S.L. (2006) My approach to the pathology of the pituitary. Journal of Clinical Pathology, 59 (12), 1245–1253.

Andersen, C.E. and McLaren, K. (2003) Best practice in thyroid pathology. Journal of Clinical Pathology, 56 (6), 401–405.

Asa, S.L., Puy, L.A., Lew, A.M. et al. (1993) Cell type-specific expression of the pituitary transcription activator Pit-1 in the human pituitary and

pituitary adenomas. Journal of Clinical Endocrinology and Metabolism, 77 (5), 1275–1280.

Baloch, Z.W. and LiVolsi, V.A. (2007) Our approach to follicular-patterned lesions of the thyroid. Journal of Clinical Pathology, 60 (3), 244–250.

Baloch, Z.W. and LiVolsi, V.A. (2000) Newly described tumours of the thyroid. Current Diagnostic Pathology, 6 (3), 151–164.

Bishop, P.W. (2002) An immunohistochemical vade mecum. Current Diagnostic Pathology 8 (2), 123–127. Available online at: http://www.e-

immunohistochemistry.info (accessed March 2007).

Biswas, S. and Rodeck, C.H. (1976) Plasma prolactin levels during pregnancy. British Journal of Obstetrics and Gynaecology, 83 (9), 683–687.

Damiani, S., Fratamico, F., Lapertosa, G. et al. (1991) Alcian blue and epithelial membrane antigen are useful markers in differentiating benign

from malignant papillae in thyroid lesions. Virchows Archiv A Pathological Anatomy and Histopathology, 419 (2), 131–135.

Chau, P. and Chan, J.K.C. (2003) Fine-needle-aspiration-induced histologic changes. Current Diagnostic Pathology, 9 (2), 77–147.

Gaffey, M.J., Traweek, S.T., Mills, S.E. et al. (1992) Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical

study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma. Human Pathology, 23 (2), 144–153.

Hough, A.J., Hollifield, J.W., Page, D.L. et al. (1979) Prognostic factors in adrenocortical tumours. American Journal of Clinical Pathology, 72 (3),

390–399.

Johnson, S.J., Sheffield,E.A. and McNicol, A.M. (2005)Examination of parathyroid gland specimens.Journal of Clinical Pathology, 58(4), 338–342.

LiVolsi, V.A. and DeLellis, R.A. (1993) Pathology of the Parathyroid and Thyroid Glands,1

edn, Williams & Wilkins, Baltimore.

Matias-Guiu, X. (1999) Mixed medullary and follicular carcinoma of the thyroid gland. American Journal of Pathology, 155 (5), 1413–1418.

McNicol, A.M. (2003) Criteria for diagnosis of follicular thyroid neoplasms and related conditions, in Recent Advances in Histopathology, Vol. 20

(eds D. Lowe and J.C.E Underwood), Royal Society of Medicine Press Ltd, London.

McNicol, A.M. (2001) Disorders of the anterior lobe of the pituitary, in Recent Advances in Histopathology, Vol. 19 (eds D. Lowe and J.C.E

Underwood), Churchill Livingstone, Edinburgh.

McNicol, A.M. (2000) Diseases of the adrenal cortex. Current Diagnostic Pathology, 6 (3), 171–180.

Ng, W-K. (2003) Radiation-associated changes in tissues and tumours. Current Diagnostic Pathology, 9 (2), 124–136.

Rindi, G., Azzoni, C., La Rosa, S. et al. (1999) ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation

by pathological analysis. Gastroenterology, 116 (3), 532–542.

Silva, E.G. and Balfour Kraemer, B. (1987) Intraoperative Pathologic Diagnosis. Frozen section and other techniques,1

edn, Williams & Wilkins,

Baltimore.

Sobrinho-Sim˜oes, M. and Fonseca, E. (1994) Recently described tumours of the thyroid, in Recent Advances in Histopathology, Vol. 16 (eds P.P.

Anthony, R.N.M MacSween and D.G. Lowe), Churchill Livingstone, Edinburgh, pp. 213–229.

Sobrinho-Sim˜oes, M., Magalh˜aes, I., Fonseca, E. et al. (2005) Diagnostic pitfalls in thyroid pathology. Current Diagnostic Pathology, 11 (1), 52–59.

Stephenson, T.J. (1997) Criteria for malignancy in endocrine tumours, in Recent Advances in Histopathology, Vol. 17 (eds P.P. Anthony, R.N.M

MacSween and D.G. Lowe DG), Churchill Livingstone, Edinburgh, pp. 93–111.

Sternberg, S.S. (ed) (1997) Histology for Pathologists,2

edn, Lippincott Williams & Wilkins, Philadelphia.

Symmers, W. St. C. (ed) (1978) Systemic Pathology, Vol. 4, 2

edn, Churchill Livingstone, London.

Weiss, L.M. (1984) Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumours. American Journal of Surgical

Pathology, 8 (3), 163–169.

Web site

RCPath, Standards and Datasets for Reporting Cancers. www.rcpath.org.uk (accessed July 2006).

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Skin 281

20. Skin

Normal

Possesses adnexal structures (unlike squamous mucosae

) and structure varies with site

Epidermis: contains many S100 +ve basal melanocytes, many CD1a +ve Langerhans dendritic cells

scattered throughout and a few CD20 +ve suprabasal Merkel cells. Toker cells (CK7 +ve) are present

in the nipple epidermis and should not be mis-diagnosed as Paget’s disease. The stratum corneum is

thickest in thick skin (palms and soles) where it may display a lower stratum lucidum

Dermis: the superﬁcial papillary dermis is loose (areolar) connective tissue with vertical components

constituting the dermal papillae and investments extending down the adnexa as adventitial dermis.It

contains the superﬁcial vascular plexus in its deepest part. The reticular dermis is less cellular dense

collagenous tissue with thick collagen bundles parallel to the skin surface and contains the deep capillary

plexus in its deepest part. Elastic ﬁbres are normally present throughout and ↑with age

Mast cells are more numerous in distal (glove and stocking) sites than proximal and have been measured

in adults at 108/mm

distally and 77/mm

proximally (≈ 21/hpf and 15/hpf respectively) and there is

an overlap in counts between normals and patients with mastocytosis

Glabrous skin occurs near the transition to the mucosae of internal tracts (e.g. labia minora, penile shaft

and outer layer of foreskin, perianal region, nipples, eyelids and lips) and is recognised by the presence

of sebaceous glands that secrete directly onto the epidermis (rather than into hair shafts)

For normal hair histology see the section on ‘Hair and Alopecia’, p. 295

Painful Lumps in the Skin / Subcutis

Traumatic neuroma

Eccrine spiradenoma

Angiolipoma (if multiple and symmetrical consider Dercum’s adiposis dolorosa)

Blue rubber bleb naevus (a syndromic vascular naevus)

Angioleiomyoma

Glomus tumour

Schwannoma (incl. granular cell tumour)

Pilomatrixoma

Endometriosis

Neuroﬁbroma

Dermatoﬁbroma

Traditionally, this group is

composed of lumps that are

associated with spontaneous

pain – even if sporadic – not

just tenderness.

Lesions Affecting the Palms / Soles

Dishidrotic eczema (pompholyx): tense intraepidermal bullae, spongiosis, mild inﬂammation

Friction / heat blister: intraepidermal clear ﬂuid bullae without inﬂammation

Volar psoriasis

◦

syphilis

Erythema multiforme (bullous form may show the Nikolsky sign i.e. the blister can be shifted)

Keratoderma blenorrhagicum (psoriasis-like pustular histology)

Epidermolysis keratosis palmaris et plantaris

Scabies / dermatophytes

Arsenic / tar keratosis (looks like a ﬂat SK – it is not usually dysplastic)

Tumours: eccrine poroma (! not BCC), acral melanocytic naevi / melanoma, verrucae, etc.

with the exception of sebaceous lobules in some mucosae e.g. Fordyce spots in the cheeks, lips and tongue (not to be confused with

angiokeratoma of Fordyce or Fox-Fordyce disease)

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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Skin 282

Epidermal Lesions (Squamous and Basal Cell)

Pseudoepitheliomatous Hyperplasia (PEH)

Shows maturation from basaloid to squamous cells (unlike most invasive SCC)

Occurs:  at the edge of chronic ulcers

 with extramammary Paget’s disease

 with granular cell tumours

 with T-cell lymphomas (d/dg lymphoepithelial carcinoma in the nasopharynx)

 in the wall of thymic cysts

The Borst-Jadassohn Phenomenon

Clonal BCP

Clonal Bowen’s

Hidroacanthoma simplex, eccrine poroma

Epidermodysplasia verruciformis

d/dg metastasis (e.g. of bronchial SmCC to the skin

)

Epidermolysis

Seen in viral warts, congenital ichthyoses, linear epidermal naevus, BCP, epidermolytic acanthoma, at

the edge of SCC and in other lesions (! do not confuse with acantholysis)

Epidermal perinuclear halos, hypergranulosis and large granules

Epidermal Cyst (and related entities)

Epidermal cyst =

◦

retention cyst of pilosebaceous infundibulum or

◦

epidermal implantation cyst

No rete ridges or dermal papillae in retention type (else consider d/dg dermoid / implantation / pigmented

hair cyst)

If partly trichilemmal keratinisation = infundibular cyst; if all trichilemmal = trichilemmal cyst

If retention-type and <1mm  = milium (d/dg miliarium [clin. ‘prickly heat’ / ‘sweat rash’] =inﬂam-

matory retention cyst of sweat duct). Do not confuse any of these with colloid milium (p. 300).

If multiple on scalp and face consider Gardner’s syndrome

d/dg epidermoid cyst (dermoid): these don’t just have a proper epidermis-like lining (as epidermal

cysts must have) but also a proper dermis-like investment (rete, adnexa, etc.). A traumatic epidermal

implantation cyst may have rete (= implantation dermoid)

d/dg see sections on ‘Vellus hair cyst’ (p. 295) and ‘Dilated pore of Winer’ (p. 292)

Acanthoma

The term cannot be used unqualiﬁed (otherwise consider d/dg prurigo nodularis)

Types: clear cell, large cell, epidermolytic and the following:

Pilar sheath acanthoma: keratin-ﬁlled endophytic basaloid proliferation replaces hair follicle

Warty dyskeratoma (solitary KF): endophytic and crateriform with acantholysis, dyskeratosis and

laminated keratin. The base shows dermal villi / papillae lined by a single layer of basal cells

Keratoacanthoma: histologically indistinguishable from well-diff SCC

Seborrhoeic Keratosis (SK, Basal Cell Papilloma)

A hyperkeratotic, exophytic, papillomatous growth with a mixture of squamous and basaloid cells

Typically show a ‘stuck on’ exophytic appearance when the slide is viewed without magniﬁcation

In acanthotic SK the basaloid cells predominate, in others (e.g. hyperkeratotic SK) the squamous cells

Horn cysts are usu. orthokeratotic (but mixed and parakeratotic forms occur

)

Basaloid cells in solid, reticulated (‘adenoid SK’) or Borst-Jadassohn (‘clonal SK’) conﬁgurations

Flat SK (incl. the clinical lesions called ‘stucco keratosis’)

Papillomatosis and ‘church spire’ hyperkeratosis. Squamous cells usu. outnumber basaloid ones

d/dg linear epidermal naevus, ﬂat viral wart and acrokeratosis verruciformis of Hopf – only clinical

features can distinguish between these

unlike 1

◦

NEC of the skin (Merkel cell) which usually spares the epidermis with a Grenz zone

pure parakeratotic forms are known as ‘squamous pearls’ and are most commonly seen in SCC

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Skin 283

Pigmented SK

Pigmented basaloid keratinocytes

Melanotic SK (Melanoacanthoma)

Intermingled pigmented dendritic melanocytes ++, non-pigmented basaloid keratinocytes

Horn cysts are few / absent

Irritated SK

SK with a host response and squamous eddies

± regression / acantholysis

Inverted follicular keratosis

Endophytic ± exophytic component

Bulbous downgrowths, squamous eddies ++, mitoses ++

Stromal inﬂammation

d/dg keratoacanthoma, BCC (but the typical BCC stroma is absent), viral wart

Plantar Wart (Verruca Plantaris, Myrmecia Wart)

HPV 1, sole/palms/ungual, painful (unless mosaic type i.e. multiple ≈ conﬂuent warts)

Childhood form resolves (months), adult becomes chronic ± progression to verrucous carcinoma

Arch.: crateriform parakeratotic plug and myrmecial downgrowths ± cysts lined by warty epithelium

No exophytic component (but the keratin may rise above the surface)

Prominent koilocytosis

Active growth phase: large eosinophil and basophil keratohyalinegranules and eosinophilic intranuclear

inclusions (d/dg molluscum contagiosum inclusions)

Plane Wart (Verruca Plana)

HPV 2 / 5, women and children, face/shin/dorsum, K¨obner phenomenon (i.e. occurs at sites of trauma)

Not much papillomatosis – and parakeratosis is not a feature

Koilocytosis and basket-weave hyperkeratosis

Dyskeratosis, perivascular chronic inﬂammation ± RBC extravasation

Epidermodysplasia Verruciformis (EV)

HPV5/8,familial (rare and pre-malignant), sporadic (HIV-assoc

EV-like lesions – multiple)

Like a large cell acanthoma but with cytological atypia and prominent keratohyaline granules

Large cells are clearer and may form suprabasal Borst-Jadassohn-like nests

Clear Cell Acanthoma (of Degos)

Raised moist red lesion on (usu.) legs of older adults

Exophytic smooth proliferation of pale (not large) keratinocytes (glycogen ++, melanin −ve)

Intermingled occ. intraepidermal PMN

Well-demarcated from normal epidermis and adnexal structures spared

d/dg large cell acanthoma (vide infra) and hidroacanthoma simplex (p. 292)

Actinic Keratosis (AK)

Sun-exposed skin

Dermis: solar elastosis of collagen ± telangiectasia and inﬂammation

Basal epidermal dysplasia with adnexal sparing (→ alternating ortho and parakeratosis)

Large cell acanthoma

Epidermal plaque with (polyploid) cells 2× normal size, normal NCR and basket-weave orthokeratin

Rete pegs broader / ﬂatter / absent

d/dg EV / EV-like lesions / verruca plana} but these all have warty changes of the granular layer

Bowenoid actinic keratosis (vs. Bowen’s disease)

Clinical features and distribution help in making the distinction

Bowen’s disease involves the adnexal structures (Bowenoid AK does not)

Bowenoid AK dysplasia may not be uniformly full-thickness (! but true Bowen’s may not be full-

thickness at its periphery)

unlike horn cysts or pearls, eddies are non-keratinising (not even parakeratinising)

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Skin 284

Naevus Sebaceus of Jadassohn (incl. Organoid Naevus)

Present from birth, usu. on head (± local trauma); epidermal and sebaceous features ↑ with age

↓ N˜o of terminal hair follicles in subcutis (abortive hair microcysts may be seen)

Epidermal hyperplasia: verrucous (= organoid naevus, d/dg linear epidermal naevus) or trichoblastic

basaloid proliferations (d/dg BCC)

Variably ↑n˜o of sebaceous lobules (may show cystic spaces and may directly connect to epidermis)

± Other adnexal elements: apocrine / eccrine glands, smooth muscle straps, etc.

±Neoplasia e.g. syringocystadenoma papilliferum, BCC (true BCC is uncommon cf. d/dg trichoblastic

basaloid proliferations)

Basal Cell Carcinoma (BCC)

Has characteristic stroma (with amyloid in 50%): myxoid, desmoplastic or keloidal

Metastatic risk ∝ size, depth of invasion and PMHx of RadioRx or immunosuppression

May be surrounded by AK change .

. do levels if this is all you see on a punch Bx for ‘?BCC’

Immuno of basaloid cells: +ve for Bcl-2 (≈ all cells), CD10, Ki-67 (>20%); −ve for CD34, CK20,

CK15

Immuno of stroma: +ve for stromelysin 3, −ve for CD34

d/dg: eccrine poroma (esp. on palms/soles – where true BCC almost never occurs)

d/dg trichoepithelioma or its sclerosing variant (= sclerosing epithelial hamartoma, esp. if in children)

d/dg basaloid proliferations (above DF, ﬁbrous papule, myxomas or naevus sebaceus of Jadassohn –

! but true BCC may co-occur with these): lack inﬁltrative arch., are restricted to stimulus lesion, may

contain CK20 +ve Merkel cells; mitoses and p53 +ve cells are rare

d/dg sebaceous tumours vs. clear cell BCC

d/dg AdCC or eccrine tumours vs. adenoid BCC

d/dg basaloid follicular hamartoma has altered stroma but lacks mitoses, apoptoses and retraction

clefts

Variants

Fibroepithelioma of Pinkus (slender reticulate strands) d/dg eccrine syringoﬁbroadenoma / adenoid SK

Adenoid (acid mucin, mucin not seen within the cells and the cells don’t show secretory morphology)

Metatypical: BCC merges into squamoid / spindled morphology ± squamous pearls but no well-

demarcated foci of typical SCC (otherwise = basisquamous carcinoma, esp. if unusually inﬁltrative)

Superﬁcial ‘multicentric’ and morphoeic types (↑ risk of local recurrence, d/dg desmoplastic trichoep-

ithelioma)

BCC with trichilemmal differentiation (incl. keratin whorls/plugs without other squamoid features)

Others: micronodular, cystic (±haemorrhage or acid mucin), signet ring, myoepithelial, pigmented (=

melanin), clear cell (and true sebaceous differentiation), BCC with monster cells (no prog. implication),

etc.

Squamous Cell Carcinoma (SCC)

Def

: a tumour of squamous differentiation with invasion

SCC variants

Rhabdoid SCC, acantholytic SCC (vide infra), verrucous SCC (vide infra)

Spindle cell SCC (previous trauma/radioRx, CK and vimentin +ve, desmosomes on EM)

Papillary SCC: an exophytic pedunculated papilloma with obvious cytological atypia and mitoses in

the squamotransitional lining (± superﬁcial clear cell change); keratin pearls and frank invasion may

be absent. d/dg verrucous Bowen’s is not an exophytic papilloma

Keratoacanthoma-like SCC (some pathologists do not believe keratoacanthoma can be diagnosed mor-

phologically, so when the morphological features of a keratoacanthoma are seen the lesion is diagnosed

as ‘a well diff keratoacanthoma-like SCC’ with a statement about excision).

⎫

⎪

⎬

⎪

⎭

Grading SCC

Broders’ Grade:

I >75% differentiated ≡ ‘well differentiated’ The amount of ‘differentiation’ in

II 25–75% diff ≡ ‘moderately diff’ this grading system is, by convention,

III <25% diff ≡ ‘poorly diff’ taken to mean the amount of

IV no differentiation ≡ ‘undifferentiated’ keratinisation.

Some dermatopathologists prefer a ‘grading’ based on the depth of invasion:

 high grade: invades beyond the level of the eccrine glands

 low grade: does not invade beyond the level of the eccrine glands

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Skin 285

Differential diagnoses

Pseudoepitheliomatous hyperplasia: SCC is characterised by abrupt maturation (keratinisation) i.e.

without the progressive maturation from a basal layer that is typical of PEH

Inverted follicular keratosis (irritated BCP with squamous eddies)

Metatypical BCC

Melanoma (spindle type)

Proliferating pilar tumour is circumscribed, has trichilemmal keratinisation, a basal layer, hyaline base-

ment membrane, rare mitoses and mild or absent atypia ± a simple pilar cyst component

Acantholytic SCC (Carcinoma Segregans)

Esp. head and neck or recurrent SCC after radioRx

Pseudoglandular spaces (d/dg ASC / MEC – but SCC has hyaluronic acid not neutral mucin)

Hypertrophied and acantholytic sweat ducts

Pseudoangiosarcomatous pattern – d/dg:  not multifocal

 focally there is better SCC differentiated areas

 attachment to epidermis

 EM shows desmosomes not Weibel-Palade bodies

Verrucous Carcinoma

Sole (cuniculatum), genitoperineal (Bushke-Lowenstein), mouth (ﬂorid papilloma): mid-aged men

Complications: sinuses and bony destruction; mets are rare

Arise within a viral wart

Exophytic component: hyperkeratotic papillary ± parakeratosis

Endophytic component:

 deep bulbous keratinised processes (often beyond eccrine glands and into subcutis)

 keratin and necrosis → sinuses

 intercellular bridges and glassy cytoplasm

 intraepithelial abscesses

 dense peritumoural chronic inﬂammation

d/dg

 viral wart: if superﬁcial / fragmented can’t distinguish .

. repeat with deeper biopsy

 keratoacanthoma: history (smooth hemispherical papule) and depth (not beyond eccrine)

 conventional SCC:  if any foci of cytological malignancy, it is not verrucous carcinoma

 if there are ﬁliform projections at the base, it is not verrucous car-

cinoma

Soft Tissue and Histiocytic Lesions

Angiokeratoma Circumscriptum

Solitary: an isolated occurrence

Multiple: ﬁngers (angiokeratoma of Mibelli), scrotum (of Fordyce), widespread (Fabry disease)

Papillary dermis: blood capillary ectasia surrounded by and closely applied to the rete peg basal layer

Superﬁcially: acanthosis and hyperkeratosis; deeper: no deep component

d/dg: verrucous haemangioma (has a deep component); lymphangioma circumscriptum (no blood)

Myoﬁbromatous Lesions

These include: dermatomyoﬁbroma, adult myoﬁbroma and myoﬁbromatosis

Glomus Tumours

Tumours of thermoregulatory ‘myoid’ vascular wall cells; any body site (but painful if superﬁcial)

There are 3 components:

◦

glomus cells,

◦

smooth muscle and

◦

angiomatoid vessels

Glomus cells: monotonous, round, pale cytoplasm (PAS-enhancing rim +ve for pericellular reticulin

and collagen IV) with central round nuclei; stroma may be hyaline ± myxoid with many nerve twigs

Variant: solid – glomus cells predominate in a nested / organoid pattern

Variant: glomangioma (angiomatoid vessels with a peripheral ‘lining’ or islands of glomus cells)

Variant: glomangiomyoma – components

◦

and

◦

are prominent

Variant: inﬁltrating glomus tumour – has ↑ risk of local recurrence

Malignancy (glomangiosarcoma): mitoses and ↑cellularity and cytol. atypia / frankly sarcomatous areas

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Skin 286

Immuno (glomus cells): +ve for SMA, MSA, ±desmin; −ve for CK, S100, CgA, calretinin, inhibin

d/dg: haemangioma, AVM, HPC, naevus, acrospiroma, carcinoid, paraganglioma (p. 279)

d/dg myopericytoma / glomangiopericytoma / myoﬁbromatosis: features in between glomus and HPC

d/dg glomus coccygeum: this is a normal macroscopic structure (several mm ) just anterior to the tip

of the coccyx and may have satellite foci. Knowledge of its existence and CPC avoid misdiagnosis

Fibrous Papule of the Face (Nose)

◦

dilated blood vessels,

◦

ﬁbrosis and

◦

large ﬁbroblasts

May have an overlying basaloid epidermal proliferation (! not d/dg BCC)

Infantile Digital Fibromatosis

Low power: non-speciﬁc mass of proliferating cellular ﬁbrous tissue

High power: eosinophilic globules in the cytoplasm of the plump spindle myoﬁbroblast cells

Eosinophilic globules are also seen in the stromal cells of ﬁbroepithelial tumour of the breast

Histiocytoses

CLASS I histiocytoses: Langerhans cell / histiocytosis X (HX)

See pp. 57–58.

CLASS II Histiocytoses: non-Langerhans / indeterminate cell and macrophage

Xanthogranuloma (Juvenile / Adult) (see p. 325):

 contains a mixture of histiocytes from the whole spectrum of the Zelger morphological sub-

types: vacuolated, xanthematised, scalloped, oncocytic and spindled

 xanthematised (Touton) giant cells are classic but other type occur

 has admixed chronic inﬂam

cells (may have eos. ++ → d/dg HX but in xanthogranuloma

histiocytes are S100 −ve, CD1a −ve, CD68 strongly +ve)

 spindle cell variant (esp. in juvenile) → d/dg ﬁbroblastic soft tissue lesions

 d/dg dermatoﬁbroma: storiform areas, haemosiderin, sparse foci of lipidisation, epidermal

changes, prominent vasculature and stromal monster giant cells favour DF, also CPC

Reticulohistiocytoma (FXIIIa +ve)

Multicentric reticulohistiocytosis (FXIIIa −ve)

Xanthomas / xanthelasmas

Xanthoma disseminatum: d/dg HX, but xanthoma disseminatum has:

 good prognosis (unless respiratory tract involved)

 giant cells are common

 scattered eosinophils

 spindle and scalloped multinucleate histiocytes which are S100 −ve, CD1a −ve, FXIIIa +ve

and CD68 very strongly +ve (cf. only weak staining in HX)

Rosai-Dorfman disease

Other rare conditions (e.g. Erdheim-Chester disease, benign cephalic histiocytosis, etc.)

d/dg reactive histiocytic lesions:

 epithelioid / foreign-body histiocyte reactions

 necrobiosis-associated granulomas (e.g. GA, rheumatoid nodules, necrobiosis lipoidica)

 necrotic / necrobiotic xanthogranuloma (assoc

with haematological disease)

 haemophagocytic syndrome-associated inﬁltrates

CLASS III histiocytoses: malignant histiocytoses

Rare, CD68 +ve, exclude other tumours / lymphomas: refer to specialist texts

DF, DFSP, Kaposi sarcoma, Desmoids, Juvenile Xanthogranuloma, Atypical Fibroxanthoma (AFX),

Vascular and Other Soft Tissue Lesions

See Chapter 21: Soft Tissues.

Melanocytic Lesions

Pagetoid Melanocytosis (PM)

Malignant melanoma

Spitz / Reed naevus

Naevi of: palms, soles, vulva, genital skin, infants

Recurrent / traumatised naevus (‘pseudomelanoma’)

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If present in dysplastic naevus, it is limited to the lower half of the epidermis

No benign lesion has lateral extension of the PM

No benign lesion has cytological atypia of the Pagetoid cells (! unless recent UV exposure)

PM is not seen in ordinary naevi

d/dg epithelial (true Paget’s, Bowen’s, Pagetoid AK, 2

◦

CA, adnexal CA) or lymphohistiocytic cells

Mitoses in Benign Melanocytic Lesions

If you ﬁnd one, search for others

An isolated normal mitotic ﬁgure may occur in:

 any benign naevus if of normal form and there are no other atypical features

 recurrent / traumatised naevus

 the clonal component of a clonal naevus

Regression in a Melanocytic Lesion

1. Chronic inﬂammation (usu. lymphohistiocytic)

2. Vascular proliferation, vascular ectasia

3. Lamellar ﬁbrosis parallel to the epidermis

4. Melanophages

d/dg stromal features of atypical naevi: evidence of melanocyte destruction/loss favours regression

Ephelis

Normal epidermis

↑ Pigmentation, normal numbers of melanocytes

d/dg caf´e au lait spots: these may have big pigment granules (giant melanosomes) unlike ephelides

Becker’s Pigmented Hairy Epidermal Naevus

Nearly normal skin: accentuated normal epidermal ridge pattern

Mild ↑ melanocytes and pigmentation

Very mild chronic inﬂammatory inﬁltrate

Blue Naevi

Ito (claviculoscapulohumeral) and Ota (ophthalmomaxillary) naevi are blue naevus variants

d/dg melanoma: because blue naevi may go deep with a rounded margin and asymmetric pigment

d/dg pigmented NF: difﬁcult – Wagner-Meissner bodies and assoc

NF-1 favour NF

Common blue naevus

Dendritic cells with ﬁne melanin granules



two cell

Melanophages with coarse melanin granules types

Cellular blue naevus

Dendritic cells (pigmented)

Balls and bundles of small non-pigmented spindle cells with uniform oval nuclei

Atypical cellular blue naevus: bizarre (e.g. giant) cells ± nuclear pleom. (but sparse mitoses and no

necrosis)

Combined blue naevus

Blue naevus cells (! do not mistake for the deep pigmentation seen in melanoma)

Ordinary naevus cells

Malignant blue naevus

↑ Mitoses, necrosis and pleom. (incl. nuclear atypia and macronucleoli): d/dg metastatic melanoma

Recurrent Naevus (Pseudomelanoma)

Usu. after shave Bx but can also occur after trauma (traumatised naevus)

Examine the previous Bx to rule out an atypical melanocytic lesion or melanoma

↑ Epidermal melanocytes

Single cells and nests

⎫

⎪

⎬

⎪

⎭

Only in the region of the dermal scar

Variable pigmentation

Random cytological atypia

An isolated normal mitosis may be seen

Residual benign naevus beneath dermal scar

! Do not confuse the dermal scarring with the ﬁbrosis of a regression reaction to melanoma

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Neurotised Intradermal Melanocytic Naevus vs. Solitary Circumscribed Neuroma

Neuroma has a partial EMA +ve capsule and shows scattered neuroﬁlament +ve axons admixed in it

Neuroma has artefactual peripheral clefts, fascicular arch. ± ancient change / PEH

Halo Naevus (of Sutton)

Usu. symmetrical

Random ‘degenerative’ atypia

Mitoses are rare (and superﬁcial)

Heavy mononuclear inﬁltrate throughout the lesion but esp. at the periphery

No expansile nests

Downward maturation

Clonal Naevus

Discrete aggregates of epithelioid melanocytes are present in the upper half of a usual naevus:

 contain dusty pigment and surrounded by melanophages

 an isolated normal mitosis may be present (if more, think melanoma)

 aggregates are not inﬁltrative or expansile (cf. melanoma)

 mild cytological atypia with small nucleoli (if bigger nucleoli, think melanoma)

d/dg melanoma arising in a naevus (do levels and look for the above features)

d/dg deep penetrating naevus (but the clonal component is superﬁcial in clonal naevus)

Atypical Nodular Proliferations in a Congenital Naevus

Big congenital naevus with a nodule

Expansile dermal nests

Uniform cytological atypia

Mitotic ﬁgures are rare

There are areas of transition between the nodule and the surrounding naevus

Naevus of Acral / Genital Skin (Flexural Naevus)

Usu. <1cm  and histologically circumscribed

Architectural atypia (often papillomatosis in genital ones)

Nests: variable size/shape (esp. vertical ovals) with cohesive cells and retraction cleft around the nest

Mild random cytological atypia

Occasional single cells rise in the epidermis (Pagetoid) – but usu. limited to centre of the lesion

Genital / Flexural: occ. dermal mitoses – d/dg melanoma (but melanoma usu. occurs in the elderly)

Acral Naevi: a junctional shoulder (i.e. junctional component overshoots) and dermal ﬁbrosis are typical

 d/dg dysplastic naevus: no lamellar ﬁbrosis or lentiginous component

 d/dg melanoma: melanoma is favoured by:  irregular acanthosis

 widespread PM

 dermal component atypia / mitoses

Infantile Naevus / Neonatal Naevus

Pagetoid melanocytosis

Mild cytological atypia

An occasional dermal mitosis

d/dg melanoma: melanoma is expansile with more atypia and mitoses throughout the lesion ±necrosis

with lack of downward maturation

Lentigo Simplex

± Familial syndromes, not actinic, no malig. potential, genital ones may be large and variegated

Rete ridge elongation (or broad acanthosis in genital ones)

↑ Numbers of melanocytes (not atypical)

↑ Pigmentation

Lentigo Senilis (Actinic Lentigo)

Elderly, actinic distribution, multiple, reticulated black ink spot variant may be worrying clinically

Bud-like rete elongation ± rete fusion

Hyperkeratosis incl. keratin cysts (i.e. BCP-like)