Histomorphological spectrum of leprosy.pptx

1. Types of leprosy
Tuberculoid Leprosy (TT)
Borderline Tuberculoid (BT)
Borderline Borderline (BB)
Borderline Lepromatous (BL)
Lepromatous Leprosy (LL)
2. Staining of acid fast bacilli

1. HISTOMORPHOLOGICAL SPECTRUM OF LEPROSY Dr. Divya Panda Assistant Professor Department of Pathology Bhaskar Medical College 19-09-2025

2. Leprosy Causative - Mycobacterial leprae Sequence of disease pathogenesis is complex, chronic and depends on host parasite immunologic responses . Best example of a disease showing - immunopathologic spectrum whereby the host immune reaction to the infective agent none to marked.

3. Progression of leprosy

4. Ridley- Jopling Classification (1966) ( Immunohistological ) Most widely accepted – academic & research purposes -Spectral concept of leprosy Tuberculoid Leprosy (TT) Borderline Tuberculoid (BT) Borderline Borderline (BB) Borderline Lepromatous (BL) Lepromatous Leprosy (LL)

5. Staining of Mycobacterium Leprae Bacilli The classical method for demonstrating leprosy bacilli in lesions is a modified Ziehl– Neelsen stain. The Fite methods are the most commonly used. Methenamine silver stains are also useful in detecting fragmented acid-fast bacilli.

6. The standard enumeration of leprosy bacilli in lesions—the bacterial index (BI)—follows Ridley’s logarithmic scale (which applies to both skin biopsies and slit skin smears). BI = 0: no bacilli observed BI = 1: 1 to 10 bacilli in 10 to 100 high-power fields ( hpf , oil immersion) BI = 2: 1 to 10 bacilli in 1 to 10 hpf BI = 3: 1 to 10 bacilli per hpf BI = 4: 10 to 100 bacilli per hpf BI = 5: 100 to 1,000 bacilli per hpf BI = 6: >1,000 bacilli per hpf Solid-staining bacilli indicate that the organisms are capable of multiplication. Fragmented (beaded) and granular acid-fast bacilli indicate that they are dead. Ridley's logarithmic scale for Bacteriological Index (BI) 

7. Immunocytochemistry – anti-BCG antibody limited role. polyclonal anti-BCG antibody In untreated lesions, it will not detect small numbers of bacilli if ordinary histochemical methods have proved negative. Has a role in demonstrating the presence of leprosy antigen after the bacilli have fragmented , been partly digested by macrophage enzymes, and lost their acid-fast staining quality.

8. Key players Lymphocyte Macrophage – activated versus foamy cells Granuloma formation Langhans giant cells Dermal nerves Plasma cells Bacteriological index

9. Lepromatous leprosy Initially has cutaneous and mucosal lesions with neural changes occurring later. The lesions are numerous and symmetrically arranged. There are three clinical types: macular, infiltrative-nodular, and diffuse. The lesions themselves are not notably hypoesthetic , involvement of the large peripheral nerves, disturbances of sensation and nerve paralyses develop. Mc - ulnar, radial, and common peroneal nerves Lucio leprosy - shows diffuse infiltration of the skin without nodules.

10. Lepromatous leprosy -Hp Extensive cellular infiltrate that is separated from the flattened epidermis by a narrow grenz zone of normal collagen ( grenz -border- German) Mild-to-moderate, superficial and deep, perivascular and periadnexal infiltrate of foamy histiocytes. The infiltrate may cause the destruction of the cutaneous appendages and extends into the subcutaneous fat.

11. Lepromatous leprosy In florid lesions, the macrophages have abundant eosinophilic cytoplasm and contain a mixed population of solid and fragmented bacilli (BI = 4 or 5) Bacilli if solid, may be packed like cigars, globi There is no macrophage activation to form epithelioid cell granulomas. Lymphocyte infiltration is not prominent, but there may be many plasma cells.

12. Lepromatous leprosy In time, and with antimycobacterial chemotherapy, degenerate bacilli accumulate in the macrophages— the lepra cells or Virchow cells —which then have foamy or vacuolated cytoplasm

13. Lepromatous leprosy Acid-fast bacilli, mostly solid, in large numbers (Wade-Fite stain)

14. Demonstrating AFB on SSS in clumps/ globi (100X).

15. Numerous isolated acid-fast bacilli forming globi .

16. Lepromatous leprosy. Macrophages and endothelial cells of the capillary contain solid acid-fast bacilli (Wade-Fite stain).

17. Histoid Leprosy Histoid leprosy shows the highest loads of bacilli (frequently, the BI is 6), and the majority are solid staining, arranged in clumps like sheaves of wheat. The macrophage reaction is unusual in that the cells frequently become spindle shaped and oriented in a storiform pattern, similar to those of a fibrous histiocytoma. The epidermis may be stretched over such dermal expansile nodules

18. Histoid leprosy Well-demarcated cutaneous and subcutaneous nodules resembling dermatofibromas A histoid lesion, with spindle cell proliferation of macrophages, resembling a storiform tumor. In histology, the storiform pattern describes a swirling, whorled arrangement of spindle cells that resembles a straw mat or woven fabric, with cells aligned in short bundles emanating from a central focus. 

19. Borderline Lepromatous Leprosy (BL) The lesions of BL leprosy are less numerous and less symmetrical than LL lesions

20. Histopathology of BL The important difference b/w LL and BL leprosy histology is that in BL, the lymphocytes are more prominent and there is a tendency for some activation of macrophages to form poorly to moderately defined granulomas. Perineural fibroblast proliferation , forming an “onion skin” in cross section, is typical. Foamy cells and globi are not prominent. BI ranges from 4 to 5.

21. Midborderline Leprosy (BB) In BB leprosy, the skin lesions are irregularly dispersed and shaped erythematous plaques with punched-out centers. There may be small satellite lesions. Edema is prominent in the lesions.

22. Midborderline Leprosy (BB) Histopathology In BB leprosy, the macrophages are uniformly activated to epithelioid cells but are not focalized into distinct granulomas, and lymphocytes are scanty. There are no Langhans giant cells. The BI ranges from 3 to 4. Dermal edema is prominent between the inflammatory cells.

23. Borderline Tuberculoid Leprosy (BT) In BT leprosy, the lesions are asymmetrical and may be scanty. They are dry, hairless plaques with central hypopigmentation Nerve enlargement is usually found, and the lesions are usually anesthetic.

24. Borderline Tuberculoid Leprosy (BT) Histopathology Granulomas with peripheral lymphocytes follow the neurovascular bundles and infiltrate sweat glands and erector pili muscles. Langhans giant cells are variable in number and are not large in size. Granulomas along the superficial vascular plexus are frequent, but they do not infiltrate up into the epidermis. Nerve erosion and obliteration are typical.

25. Borderline Tuberculoid Leprosy (BT) Acid-fast bacilli are scanty (BI ranges from 0 to 2) and most readily found in the Schwann cells of nerves. Immunocytochemical staining for S-100 protein often demonstrates the perineural and intraneural granuloma well Fig. 21-14B)

26. Tuberculoid Leprosy The skin lesions of TT leprosy are scanty, dry, erythematous, hypopigmented papules or plaques with sharply defined edges. Anesthesia is prominent (except on the face). The number of lesions ranges from one to five. Thickened local peripheral nerves may be found. The lesions heal rapidly on chemotherapy.

27. Tuberculoid Leprosy Histopathology. Primary TT leprosy has large epithelioid cells arranged in compact granulomas along with neurovascular bundles, with dense peripheral lymphocyte accumulation. Dermal nerves may be absent (obliterated) or surrounded and eroded by dense lymphocyte cuffs. Acid-fast bacilli are rarely found, even in nerves.

28. TUBERCULOID LEPROSY

29. TUBERCULOID LEPROSY

30. Tuberculoid leprosy Granulomatous neuritis; dense lymphocytosis surrounding and eroding into the deep dermal nerve with giant cells (H&E stain)

31. TT LEPROSY In tuberculoid leprosy, there is no grenz zone unlike in borderline tuberculoid and more lepromatous forms.  The  bacilli are scarce and usually not identified with modified acid-fast stains . The close association of granulomatous response with the cutaneous nerves is a helpful diagnostic feature in tuberculoid leprosy.

32. Perineural granulomatous inflammatory infiltrate in Hansen disease (red arrow pointing to nerve)(A)(H&E, original magnification ×400). The inset shows Fite-positive rod-shaped bacteria (black arrows). 

33. Indeterminate leprosy Histopathology: Mild lymphocytic and macrophage accumulation around Neurovascular bundles Superficial and deep dermal vessels Sweat glands Erector pili muscle Focal lymphocytic invasion into the lower epidermis and into dermal nerves may be observed. Schwann cell hyperplasia is a feature but highly subjective

34. Indeterminate leprosy The diagnosis hinges on finding one or more acid-fast bacilli in the sites of predilection. Without demonstrating bacilli, the diagnosis can only be presumptive.

35. Indeterminate leprosy Sites of predilection In nerve In erector pili muscle Just under the epidermis In a macrophage about a vessel.

36. Indeterminate leprosy Slight pandermal perineurovascular and periappendageal chronic inflammation (H&E stain)

37. Neural involvement in Leprosy LL- Neural involvement tends to be slow and multiple, worsening during reactional episodes. BL- There is generalized asymmetric clinical involvement of the peripheral nerves. BB- Patients may have peripheral nerve thickening and chronic neuritis.  BT- neural trunks are asymmetrically enlarged, causing more severe neuropathy, with neural infiltration on histopathological examination.  TT-Unilateral and more acute, therefore, progressing earlier to disabilities.

38. The demonstration of acid-fast bacilli within nerves is pathognomonic of leprosy.

39. Leprosy Reactions Leprosy reactions are episodes of acute hypersensitivity characterized by the worsening of previous lesions or the appearance of new lesions, occurring before, during, or after treatment. More commonly, leprosy reactions occur in multibacillary presentations during the first three months of leprosy specific treatment and currently represent the main disease complication, requiring immediate treatment to prevent neural sequelae .

40. Leprosy Reactions Leprosy reactions can be of two types: Type 1 reaction and erythema nodosum leprosum (ENL). Type 1 occurs in approximately one-third of patients with a borderline presentation (BB/BL/BT) ENL occurs mc in LL and less frequently in BL.

41. Upgrading vs Downgrading reaction Typically, there is edema within and about the granulomas and proliferation of fibrocytes in the dermis. In upgrading reactions, the granuloma becomes more epithelioid and activated, and Langhans giant cells are larger there may be erosion of granulomas into the lower epidermis, In downgrading reactions, necrosis is much less common, and over time the density of bacilli increases . Multibacillary leprosy patients who upgrade on therapy show old foamy macrophages and degenerate bacilli admixed with newly developing epithelioid cell granulomas.

42. Type 1 reaction (Reversal Reactions) Granulomatous erosion of the epidermis; this feature is not usually encountered in nonreacting leprosy (H&E stain)

43. Erythema Nodosum Leprosum In ENL, the lesions are foci of acute inflammation superimposed on chronic multibacillary leprosy. Neutrophilic polymorphonuclear infiltrate foci, intermingled with a macrophage granulomatous response, edema, and often with evidence of vasculitis. The inflammatory process affects the dermis and hypodermis.

44. Erythema nodosum leprosum (Type 2 reaction) Macrophages with vacuoles and globi and a polymorphonuclear cell infiltrate ( H&Estain )

45. Lucio Reaction The Lucio reaction occurs exclusively in diffuse LL leprosy. It usually occurs in patients who have received either no treatment or inadequate treatment. The lesions consist of barely palpable, hemorrhagic, sharply marginated, irregular plaques. Ischemic necrosis, brought on by the vascular occlusion, leads to hemorrhagic infarcts and results in crusted erosions or frank ulcers. They are thought to result from immune complex deposition.

46. Histopathology of Lucio In the Lucio reaction, vascular changes are critical. Endothelial proliferation leading to luminal obliteration is observed in association with thrombosis in the medium-sized vessels of the dermis and subcutis. There is a sparse, largely mononuclear infiltrate. Dense aggregates of acid-fast bacilli are found in the walls and the endothelium of normal-appearing vessels as well as in vessels with proliferative changes.

47. Key players Lymphocyte Macrophage – activated versus foamy cells Granuloma formation Langhans giant cells Dermal nerves Plasma cells Bacteriological index

48. Summary Histopath Features Indeterminate TT (Tuberculoid) BT (Borderline Tuberculoid) BB (Mid-borderline) BL (Borderline Lepromatous) LL (Lepromatous) Granuloma Absent Epithelioid Epithelioid Mixed cellular Macrophages Macrophages T-lymphocytes ++++ ++++ +++ ++ ++ + Epithelioid cells Absent ++++ +++ ++ + Absent Giant cells Absent +++ ++++ Absent Absent Absent Macrophage Absent Absent + ++ ++++ ++++ Bacteriological Index 0-1 0-1 0-2 3-4 4-5 5-6+ Nerves Only lymphocytes Destroyed Damaged Identifiable Preserved for long Late destruction B cells/plasma cells Negative Negative Negative ?Present Present Present Reactions Negative Reversal reaction Reversal reaction Reversal reaction Reversal reaction / ENL ENL

49. D/d - Look at dermal nerves and epithelium! Sarcoidosis may rarely cause granulomas to form within peripheral nerves but does not appear to do so in dermal nerves . Mycobacterial skin infections such as tuberculosis , and unlike granulomatous leishmaniasis, the epidermis in TT leprosy is usually flat and nonhyperplastic . Late secondary and tertiary cutaneous syphilis is characterized by epithelioid and giant cell granulomas in the dermis , not directly involving nerves, and the epithelium is usually hyperplastic.

50. TT vs Lupus vulgaris

51. Guess the following images..

52. LL LEPROSY

53. A. Borderline Leprosy. Well-demarcated erythematous- edematous plaques and papules. B Borderline-lepromatous leprosy. Erythematous plaque with a well-defined hypochromic center , and ill-defined outer edges.

54. TT LEPROSY

55. LUPUS VULGARIS (cutaneous TB)

56. References Froes LAR Junior, Sotto MN, Trindade MAB. Leprosy: clinical and immunopathological characteristics. An Bras Dermatol. 2022 May-Jun;97(3):338-347. doi : 10.1016/j.abd.2021.08.006. Epub 2022 Apr 2. PMID: 35379512; PMCID: PMC9133310. Lever’s Histopathology of the skin , Eleventh edition